http://cmac-journal.ru/en/publication_types/9/ Recent content in 9 on КМАХ Source Themes Academic (https://sourcethemes.com/academic/) en-us Thu, 28 May 2026 10:50:08 +0000 http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p131/ Thu, 28 May 2026 10:50:08 +0000 http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p131/ <h3 id="objective">Objective.</h3> <p>Introduction. Selective digestive decontamination of the digestive tract (SDD) with non-absorbable antibiotics is considered a promising approach to reduce the risk of infections in critically ill patients. However, the widespread circulation of multidrug-resistant microorganisms, including carbapenemresistant <em>Klebsiella pneumoniae</em> and <em>Pseudomonas aeruginosa</em>, significantly reduces the efficacy of conventional SDD regimens based on colistin monotherapy. The key reason for failures is the wide «mutant selection window» – a range of antibiotic concentrations insufficient to suppress the growth of resistant subpopulations. The use of antimutant combinations of non-absorbable antibiotics may open new prospects for SDD optimization. Development and validation of a dynamic flow-through <em>in vitro</em> system for pharmacokinetic/ pharmacodynamic (PK/PD) modeling of clinical SDD regimens and evaluation of the antimutant activity of the combination of non-absorbable antibiotics colistin and rifaximin against extremely antibiotic-resistant strains of <em>K. pneumoniae</em> and <em>P. aeruginosa</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 10 clinical isolates of <em>K. pneumoniae</em> (producers of NDM, KPC, OXA-48, KPC+NDM) and 10 clinical isolates of <em>P. aeruginosa</em> (including 4 VIM carbapenemase producers). Minimum concentrations of colistin and rifaximin that prevent the selection of resistant mutants (MPC) were determined using agar plating with antibiotic. A single-chamber flow-through system was constructed that reproduces the pharmacokinetics of non-absorbable antibiotics during enteral administration. Clinical regimens of colistin, rifaximin, and their combination administration (every 8 hours for 7 days) were modeled.</p> <h3 id="results">Results.</h3> <p>MPC of colistin for <em>K. pneumoniae</em> strains ranged from 64 to 128 mg/L, for <em>P. aeruginosa</em> – 8 to 16 mg/L, which was 8–256 and 4–16 times higher than the MIC, respectively. MPC of rifaximin could not be determined within the tested concentrations for the vast majority of strains (MPC ≥256 mg/L). In the presence of rifaximin, the MPC of colistin decreased 4–8-fold for <em>K. pneumoniae</em> and 2–8-fold for <em>P. aeruginosa</em>. In static experiments, colistin (70 mg/L) and rifaximin (200 mg/L) did not prevent breakthrough growth of some strains within 24–48 hours, whereas the combination completely suppressed the growth of all strains for 7 days. In the dynamic flow-through system during monotherapy, adaptation of some microorganisms to colistin and rifaximin was observed; the combination of colistin and rifaximin ensured complete suppression of growth of all tested strains throughout the entire 7-day observation period.</p> <h3 id="conclusions">Conclusions.</h3> <p>The developed dynamic flow-through system is a convenient tool for preclinical evaluation of PK/PD parameters of antimutant combinations of non-absorbable antibiotics. The combination of colistin and rifaximin demonstrates high antimutant activity under conditions simulating SDD regimens against both <em>K. pneumoniae</em> and <em>P. aeruginosa</em>, which opens prospects for its clinical use in regions with high prevalence of antibiotic-resistant pathogens.</p> http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p124/ Thu, 28 May 2026 10:47:54 +0000 http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p124/ <h3 id="objective">Objective.</h3> <p>To investigate the bacterial and fungal microbiota of the lower respiratory tract in hospitalized patients with tuberculosis and HIV coinfection.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 378 sputum samples from 147 patients at the Novosibirsk Tuberculosis Research Institute (Ministry of Health of the Russian Federation) were collected and analyzed between 2021 and 2024. Sputum samples were obtained according to standardized protocols to minimize contamination with upper respiratory tract microflora and ensure representativeness of the lower respiratory tract biota. Samples were cultured on selective medium. Microbial identification was performed by MALDItof mass spectrometry using a Microflex instrument (Bruker Daltonics, Germany). Statistical analysis was conducted using SPSS software (version 19).</p> <h3 id="results">Results.</h3> <p>To differentiate lower respiratory tract isolates from potential contaminants, paired oropharyngeal (throat) and sputum samples were compared by quantitative culture (CFU/mL) according to established clinical criteria, with adjustments for HIV status. A total of 492 pathogenic and opportunistic microorganisms, belonging to 15 families, were isolated. Fungal microbiota accounted for 44.9% of isolates, predominantly of the family Saccharomycetaceae (mainly <em>C. albicans</em>). Bacterial microbiota constituted 51.1%, represented by <em>Enterobacteriaceae</em> (21.5%), Staphylococcaceae (9.96%), Pasteurellaceae (8.94%, and Pseudomonadaceae (5.69%). The spectrum of microorganisms varied depending on the clinical forms of tuberculosis and the type of drug resistance of mycobacterium.</p> <h3 id="conclusions">Conclusions.</h3> <p>Conclusions.The lower respiratory tract microbiome in patients with active tuberculosis and HIV coinfection is characterized by severe dysbiosis, with a predominance of fungal taxa and Gram-negative facultative anaerobes. This dysbiosis may be associated with factors such as the drug resistance profile of <em>Mycobacterium tuberculosis</em>, disease duration, combination chemotherapy, and the immunosuppressive effects of HIV. These findings highlight the need for a comprehensive approach to the diagnosis and treatment of patients with pulmonary tuberculosis and concomitant HIV infection.</p> http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p108/ Thu, 28 May 2026 10:45:55 +0000 http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p108/ <h3 id="objective">Objective.</h3> <p>To identify associations between functional polymorphisms in genes of the immune, endothelial, and coagulation systems and the severity and outcomes of sepsis to validate genetic risk predictors.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>This single-center prospective study included 124 patients aged of 1 month to 28 years with hematological malignancies, in whom 152 cases of sepsis were recorded. Genotyping of 20 polymorphic variants in 16 genes was performed using capillary Sanger sequencing. Statistical analysis included assessing the conformity of genotype distributions to Hardy–Weinberg equilibrium, comparing frequencies using the dominant inheritance model, and calculating odds ratio (OR), the Yates corrected χ² test, and p-value (2-tail).</p> <h3 id="results">Results.</h3> <p>The most significant predictor of an unfavorable course is the MCP1 -2518A&gt; G polymorphism, associated with severe acute kidney injury (AKI) (OR = 3.30; p = 0.001), the need for renal replacement therapy (OR = 5.4; p<0.0001), mechanical ventilation (p = 0.019) and mortality (OR = 2.4; p = 0.02). MTHFR c.665C > T is associated with sepsis-induced coagulopathy (OR = 2.0; p = 0.049), DIC (OR = 2.9; p = 0.003) and proinflammatory phenotype SIRS (OR = 2.17; p = 0.04). A dual role was determined for HAVCR1: c.619A&gt; G is protective against septic shock (OR = 0.42; p = 0.02) and AKI (OR = 0.34; p = 0.007); c.536T &gt; C is associated with mortality (OR = 3.7; p = 0.02). Opposite effects of IL18: -607C &gt;A – risk of renal replacement therapy (OR = 3.3; p = 0.008) and mechanical ventilation (OR = 2.4; p = 0.009); -137G &gt; C – protection against these complications (OR = 0.46 and 0.32, respectively). The context dependence of TNFα -308G &gt;A was established: it was associated with coagulopathy (OR = 4.10; p = 0.02) and protective for chronic critical illness (OR = 0.18; p = 0.001). Polymorphisms of TLR4 (c.296A&gt; G, c.596C &gt; T) and IL18 (-137G &gt; C) were associated with the risk of sepsis recurrence (OR = 4.0; p = 0.03). The TLR4 variant c.*1205G &gt;A was associated with septic shock (OR = 2.2; p = 0.04). PAI-1 4G/5G was associated with severity of AKI (OR = 2.62; p = 0.009), and the protective allelic variant CD14 c.-159C &gt; T was associated with reduced risk of chronic critical illness (OR = 0.36; p = 0.0054).</p> <h3 id="conclusions">Conclusions.</h3> <p>Genetic markers associated with the development of key sepsis complications were identified. The obtained results substantiate the usefulness of genetic testing for risk stratification and personalized intensive care in patients with sepsis.</p> http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p103/ Thu, 28 May 2026 10:43:50 +0000 http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p103/ <h3 id="objective">Objective.</h3> <p>To study structure of pathogens of community-acquired urinary tract infections (UTI) in children and adolescents under 18 years of age subpopulation of the Krasnoyarsk region as well as the activity of antimicrobials against the leading pathogen in order to optimize local empirical therapy of UTI.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 298 urine cultures were analyzed (164 in 2023 and 134 – in 2024). The urinalyses were obtained from children and adolescents with community-acquired UTI who hospitalized to the Krasnoyarsk Regional Clinical Center for Maternal and Child Health in 2023–2024. The continuous observation method and retrospective analysis were used.</p> <h3 id="results">Results.</h3> <p><em>Escherichia coli</em> was the leading etiological pathogen of community-acquired UTI in Krasnoyarsk region. Klebsiella pneumoniaе and <em>Enterococcus</em> spp. accounted in the 2-3 place in etiological structure. Of the parenteral agents, antimicrobial resistance of <em>E. coli</em> to meropenem was absent. The maximal sensitivity <em>E. coli</em> was noted for ampicillin-sulbactam and amikacin. Antimicrobial resistance of <em>E. coli</em> was recorded above 20% in relation to cefepim and 3-rd generation cephalosporins as to amoxicillin-clavulanate and cotrimaxozole. Of the oral medicines fosfomycin and nitrofurantoin activity to <em>E. coli</em> was preserved.</p> <h3 id="conclusions">Conclusions.</h3> <p>According to the data on antibacterial resistance of <em>E. coli</em> in children and adolescents with community-acquired UTI in the Krasnoyarsk region the starting drug of choice to empirical therapy of UTI in considered to be ampicillin-sulbactam for parenteral administration and fosfomycin or nitrofurantoin for oral prescription. 3-rd generation cephalosporins and amoxicillin-clavulanate cannot be recommended for empirical treatment due to the identified resistance level exceeding 20%.</p> http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p72/ Thu, 28 May 2026 10:35:41 +0000 http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p72/ <h3 id="objective">Objective.</h3> <p>To study pharmacokinetics (PK) and develop a pharmacokinetic/pharmacodynamic (PK/PD) model of linezolid for preterm infants, based on therapeutic drug monitoring (TDM) data.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The PK/PD analysis included data from therapeutic drug monitoring (TDM) of 24 premature infants, taking into account the repeated TDM procedure – a total of 27 occasions and 54 measurements of linezolid concentration. Quantitative determination of linezolid concentrations in the blood plasma of patients was carried out using the analytical method of measurement by HPLC-UV previously developed on the basis of the educational and scientific laboratory for the study of drug safety at the Department of General and Clinical Pharmacology of the RUDN University in the City Clinical Hospital No. 24.</p> <h3 id="results">Results.</h3> <p>Total clearance and volume of distribution values of linezolid in premature newborns estimated in the study were consistent with those previously reported in the literature. A significant interindividual PK variability was observed (coefficient of variation – 42-89%), resulting in poor predictability of the Сtrough and Cmax levels at the end of infusion when the standard dosing regimen of linezolid 10 mg/kg thrice daily was used. Such pronounced interindividual variability of PK parameters, combined with a relatively limited sample size, precluded probably development from the available TDM data of a multivariate regression model that could predict the individual PK parameter values for the majority of the included premature infants based on their covariates with acceptable accuracy.</p> <h3 id="conclusions">Conclusions.</h3> <p>The observed discrepancies in the dosage regimens, which are considered optimal in different published PK/PD studies for premature newborns, indicate in favor of using standard regimens only to individualize the initial dosing based on patient covariates. Further dosage adjustments should preferably be made based on the patient’s TDM data. Specialized software for Bayesian population modeling approach will allow to personalize linezolid therapy based on rare TDM measurements without waiting for the steady state, which is especially important for the premature infant population.</p> http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p50/ Thu, 28 May 2026 10:27:57 +0000 http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p50/ <h3 id="objective">Objective.</h3> <p>To study etiological structure of respiratory tract infections in patients with primary ciliary dyskinesia (PCD) across different age groups.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 173 patients with a confirmed diagnosis of PCD from various regions of the Russian Federation were examined from 2023 to 2025. The patients were divided into 4 age groups: children (0–6 years) – 42 patients; children (7–12 years) – 42 patients; adolescents (13–17 years) – 43 patients; adults (18 years and older) – 46 patients. The study employed bacteriological methods, MALDI-TOF mass spectrometry, molecular genetic methods, disk diffusion for antibiotic susceptibility testing, and statistical methods.</p> <h3 id="results">Results.</h3> <p>A comparative analysis of the etiological structure of respiratory tract infections in the four age groups of PCD patients showed that the greatest diversity of clinically significant fungal and bacterial pathogens was observed in the adolescent group – 28, and the smallest in the adult group – 24. The study revealed that <em>S. aureus</em> was most frequently detected in children and adolescents: 0–6 years – in 47.6% of cases; 7–12 years – in 64.3%; adolescents 13–17 years – in 74.4%. In the adult age group, <em>P. aeruginosa</em> predominated – in 80.4% of cases. Antibiotic susceptibility testing using the disk diffusion method revealed that 24.4% of <em>S. aureus</em> isolates were multidrug-resistant, while among <em>P. aeruginosa</em> isolates, 33.3% were multidrug-resistant. Among fungal pathogens, fungi of the genera Candida and Aspergillus were most frequently isolated.</p> <h3 id="conclusions">Conclusions.</h3> <p>The conducted study showed that in patients with PCD, the cause of respiratory tract infection (RTI) in most cases is bacterial representatives of opportunistic flora. The dominant pathogens include: <em>S. aureus</em> – 53.8%; <em>P. aeruginosa</em> – 38.7%; <em>H. influenzae</em> – 21.4%; <em>S. pneumoniae</em> – 17.9%. It was established that the complication of chronic lung infection (CLI) occurs most frequently in adulthood – 63%, and its etiological cause in 100% of cases is <em>P. aeruginosa</em>.</p> http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p4/ Thu, 28 May 2026 10:19:27 +0000 http://cmac-journal.ru/en/publication/2026/1/cmac-2026-t28-n1-p4/ <h3 id="objective">Objective.</h3> <p>To analyze the current taxonomic structure of the genus Stenotrophomonas based on genomic data, taking into account limitations associated with nomenclatural validation processes.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A reference dataset was constructed using taxonomic information from LPSN (List of Prokaryotic names with Standing in Nomenclature) and genome assemblies retrieved from the NCBI database. Pairwise average nucleotide identity (ANI) and average amino acid identity (AAI) values were calculated. Species delineation was performed using the commonly accepted threshold of ANI ≥ 95%. Hierarchical clustering was conducted using the average linkage method based on distance matrices.</p> <h3 id="results">Results.</h3> <p>Based on taxonomic information provided by LPSN, an initial reference dataset comprising 36 genomes corresponding to validly named species of the genus Stenotrophomonas was established. Pairwise ANI values confirmed clear separation of these genomes at the level of species. Analysis of pairwise AAI values revealed several genomically distinct clusters consistent with a recently proposed taxonomic framework suggesting subdivision of the genus Stenotrophomonas into multiple genera. Analysis of 2,332 Stenotrophomonas genomes from the NCBI database revealed that 15.7% had ANI values below the 95% threshold relative to reference genomes of LPSN-listed taxa, precluding assignment to any recognized species. Clustering at ANI ≥95% yielded 102 genomic clusters, some lacking genomes from LPSN-listed species. To enable classification of such genomes, an expanded reference dataset was constructed by including representative genomes of the corresponding ANI clusters. This expanded reference dataset enabled assignment of all analyzed genomes to either LPSN-listed taxa or to distinct genomic clusters lacking validated nomenclatural status.</p> <h3 id="conclusions">Conclusions.</h3> <p>Even with abundant genomic data and quantitative delineation criteria, taxonomic interpretation of genomic collections remains constrained by the lag between genome-based identification of putative new taxa and their formal description with type strain designation. Our proposed analytical approach systematically accounts for such genomes and offers a reproducible framework for analyzing the taxonomic structure of the nomen genus Stenotrophomonas amid ongoing revisions.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p524/ Sat, 24 Jan 2026 13:47:26 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p524/ <h3 id="objective">Objective.</h3> <p>To provide a genetic characterization based on whole-genome sequencing (WGS) data of <em>S. aureus</em> isolates identified in one intensive care unit (ICU) during the COVID-19 pandemic.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>WGS on Illumina MiSeq was performed, generating twenty <em>S. aureus</em> sequences isolated from patients and environmental surfaces. Bioinformatic analysis included typing, identification of antimicrobial resistance (AMR) determinants, virulence factors, plasmid replicons, and phylogenetic analysis.</p> <h3 id="results">Results.</h3> <p>Significant genetic diversity was revealed, comprising four clonal complexes (CCs): CC15 – ⁶&frasl;₂₀ (30%), CC8 – ³&frasl;₂₀ (15%), CC22 – ²&frasl;₂₀ (10%), and CC97 – ²&frasl;₂₀ (10%); while ⁷&frasl;₂₀ (35%) of isolates had an indeterminate CC. CC8 and CC22 isolates were detected exclusively on healthcare workers&rsquo; personal protective equipment (PPE). Phylogenetic analysis showed clustering with strains from diverse geographical regions. AMR genes conferring resistance to 9 antibiotic classes were identified, including β-lactams (blaZ, mecA), tetracyclines (tet(38)), and fosfomycine (fosB). Virulence genes (encoding immunesuppressing toxins, exoenzymes) were highly prevalent (&gt; 90%). Plasmid replicons (e.g., rep16, rep5a) were identified in ¹⁷&frasl;₂₀ (85%) of the isolates, indicating potential horizontal gene transfer of AMR determinants.</p> <h3 id="conclusions">Conclusions.</h3> <p>These data demonstrate a complex <em>S. aureus</em> ecosystem within the ICU, characterized by high genetic diversity, a high prevalence of AMR and virulence determinants, and a significant plasmid pool. The predominance of isolates from PPE underscores the need for enhanced infection control measures to prevent the spread of potentially pathogenic and multidrug-resistant <em>S. aureus</em> strains in the hospital setting.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p516/ Sat, 24 Jan 2026 13:45:17 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p516/ <h3 id="objective">Objective.</h3> <p>To assess quality of bacterial detection using 16S rRNA gene sequencing with accredited control materials designed for external quality control of PCR studies.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Control materials obtained as part of the ISI «FSVOK» program: «DNA detection of Mycoplasma hominis, Ureaplasma spp., Ureaplasma urealyticum, Ureaplasma parvum by PCR (STI)», were analyzed by 16S rRNA gene sequencing. The control sets of samples were presented with lyophilized solutions of M. hominis, U. urealyticum, and U. parvum genomic DNA at specified concentrations and human genomic DNA at a concentration of at least 2 × 105 copies/ml in two cycles.</p> <h3 id="results">Results.</h3> <p>We analyzed 16 control samples that were obtained in two MCI cycles. The analysis of control materials presented in the MCI program «FSVOK» using 16S rRNA gene sequencing allowed for an accurate qualitative assessment of the presence or absence of opportunistic microorganisms such as M. hominis and Ureaplasma spp. A limitation of the method is the difficulty in species identification of Ureaplasma parvum/urealyticum due to the similarity in nucleotide sequences in the V3-V4 region of the 16S rRNA. Despite the very high sensitivity of the method and the detection of other microorganisms at extremely low values (&lt; 0.1%), the negative control sample, which did not contain the target bacterial markers, did not reveal M. hominis or Ureaplasma spp in two cycles of the program, indicating the absence of contamination at all stages of laboratory research, OPK production, storage, and distribution by the MCI organizer, as well as the absence of false-positive results in the application of the 16S rRNA gene sequencing method.</p> <h3 id="conclusions">Conclusions.</h3> <p>The method allows reliable identification of M. hominis, Ureaplasma spp., U. urealyticum, U. parvum, and other bacteria in control samples, which may have clinical significance in assessing vaginal microbiocenosis, as an advantage over the PCR method designed to detect specific individual targets.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p506/ Sat, 24 Jan 2026 13:43:21 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p506/ <h3 id="objective">Objective.</h3> <p>To compare microbiota profiles of sputum and bronchial washes in patients with pulmonary tuberculosis obtained using PCR and to assess clinical significance of obtained microbial profiles.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We compared the results of sputum and bronchial washes using PCR-based test systems «Backscreen UPM» and «Femoflor 16» (DNA-Technology, Russia) in 51 patients with pulmonary tuberculosis.</p> <h3 id="results">Results.</h3> <p>The analysis revealed that the following dominant taxa of microorganisms were detected both in sputum and bronchial washes in the majority of patients: representatives of the genera Streptococcus, Veillonella, Prevotella, and Haemophilus. In most cases, the presence or absence of microorganisms in bronchial flush samples corresponded to their presence and abundance in sputum. The presence of opportunistic microorganisms in bronchial washes at levels exceeding those in sputum may indicate their proliferation in the lungs, highlighting their clinical significance. Cluster analysis revealed that in the case of localization of the tuberculosis process in the lower lobes of the lungs, the profiles of sputum and bronchial washes do not coincide more often than in the case of upper lobe localization of the process. A lower proportion of “dominant” taxa in bronchial washes was associated with a longer duration of tuberculosis treatment.</p> <h3 id="conclusions">Conclusions.</h3> <p>Bronchial washes are the preferred type of clinical material for searching the relationship between microbiota characteristics and variants of the clinical course of tuberculosis.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p494/ Sat, 24 Jan 2026 13:39:26 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p494/ <h3 id="objective">Objective.</h3> <p>Creation and evaluation of the effectiveness of an integrated system for automatic validation of microbiological reports and monitoring of antimicrobial resistance (AMR) on real time at the regional level within the Yamalo-Nenets Autonomous Okrug (YNAO).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The prospective study was conducted from October 2023 to June 2025, based on the Medical Information and Analytical Center and five largest hospitals in the YNAO. The study design included a comparative analysis of AMR monitoring status before and after the implementation of the digital platform. The objects of the study were data from 11728 microbiological reports, 12216 isolates, and the results of a survey conducted among 53 doctors. The period after implementation lasted 12 months, from June 2024 to June 2025. The primary endpoint was a comprehensive evaluation of the system based on criteria, including automatic validation level, coverage of healthcare facilities, data accessibility, and analytical capabilities. Methods for assessment included analyzing the operational data of the platform, conducting a structured survey among doctors, and assessing cost-effectiveness using an approved methodology.</p> <h3 id="results">Results.</h3> <p>After implementation, the system achieved 100% coverage of the planned healthcare facilities (5 hospitals). A total of 11728 cases were processed, of which 77,2% (⁹⁰⁵⁷&frasl;₁₁₇₂₈) generated expert reports by the system (median – 3 reports per analysis). In 19,3% of cases (²²⁶⁷&frasl;₁₁₇₂₈), high- and medium-risk reports were identified, indicating potential therapy errors. A survey of 53 doctors found that 66% (³⁵&frasl;₅₃) do not experience difficulties reading new opinion forms, and 87% (⁴⁶&frasl;₅₃) regularly read system-generated comments, with 96% (⁵¹&frasl;₅₃) finding them useful for antibiotic selection. The economic impact of the system amounts to 110 million rubles per year, with potential annual prevention of up to 14 deaths.</p> <h3 id="conclusions">Conclusions.</h3> <p>The introduction of the system for AMR monitoring and automated validation of microbiological reports in the Yamalo-Nenets Autonomous District has led to the standardization of microbiological diagnostics, increased safety of antimicrobial treatment, and the provision of upto-date epidemiological data in real-time. The system has shown significant clinical and economic benefits, demonstrating the feasibility of replicating it in other regions of the Russian Federation.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p485/ Sat, 24 Jan 2026 13:37:06 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p485/ <h3 id="objective">Objective.</h3> <p>To investigate antibiotic resistance of <em>S. aureus</em> isolates from cystic fibrosis (CF) patients with chronic lung infection and to identify its genetic determinants.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The antibiotic susceptibility of 629 <em>S. aureus</em> isolates from pediatric and adult CF patients was analyzed using the disk diffusion method and E-test in accordance with EUCAST guidelines. All strains were screened by PCR for the presence of the mecA and mecC genes. Six <em>S. aureus</em> strains were investigated using whole-genome sequencing (WGS).</p> <h3 id="results">Results.</h3> <p>Methicillin-resistant <em>S. aureus</em> (MRSA) accounted for 8% and 13% of isolates from children and adults, respectively. High resistance rates were detected for benzylpenicillin (70% in children, 33% in adults), erythromycin (31.2% and 35%), and chloramphenicol (21.1% and 23%). All strains remained susceptible to vancomycin, linezolid, teicoplanin, and quinupristin/dalfopristin. WGS of the six strains classified two as sequence type ST1 (MSSA) and four as ST8 (MRSA). The following resistance determinants were identified: 1. genes for antibiotic-inactivating enzymes and target-modifying proteins: mecA (cefoxitin), blaZ (β-lactams), aac(6&rsquo;)aph(2&rdquo;) (aminoglycosides), cat(pC194) (chloramphenicol), erm&copy; (macrolidelincosamide-streptogramin B); 2. mutations in antibiotic target genes: grlA, gyrA, and rpoB, conferring resistance to fluoroquinolones and rifampicin; 3. efflux pump genes: lmrS, norA, mgrA, mepA/R, arlR/ S,tet(K) associated with resistance to fluoroquinolones, tetracycline, macrolides, and other antibiotics, were found in all sequenced strains, which is consistent with literature data.</p> <h3 id="conclusions">Conclusions.</h3> <p>This study identified key genetic determinants of antibiotic resistance characteristic of <em>S. aureus</em> isolated from CF patients. These mechanisms encompass various strategies, including enzymatic degradation of the antibiotic, modification of the bacterial antibiotic target, and reduction of intracellular antibiotic concentration—either through decreased cell wall permeability or active efflux from the cell via bacterial efflux pumps.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p475/ Sat, 24 Jan 2026 13:35:11 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p475/ <h3 id="objective">Objective.</h3> <p>To determine the population structure of clinical <em>P. aeruginosa</em> isolates recovered from hospitals in different regions of Russia and to assess the role of high-risk clones in the dissemination of carbapenemases and carbapenem resistance.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included consecutive, non-duplicate clinical isolates of <em>P. aeruginosa</em> (N = 1379) obtained from 55 hospitals across 30 Russian cities over a 24-month period. Species identification was performed using MALDI-TOF mass-spectrometry. Antimicrobial susceptibility testing was carried out by broth microdilution. The presence of acquired carbapenemase genes (VIM, IMP, NDM, GES-2/-5) was determined by real-time PCR. Subspecies typing and assignment to known sequence types (STs) and clonal complexes (CCs) were performed by identifying single nucleotide polymorphisms (SNPs) in seven chromosomal loci used in the multilocus sequence typing (MLST) scheme. Whole-genome sequencing (WGS) and resistance gene annotation were performed for selected isolates representing the main high-risk clones.</p> <h3 id="results">Results.</h3> <p>All <em>P. aeruginosa</em> isolates were assigned to 264 genetic lineages, among which four clonal complexes corresponding to internationally recognized high-risk clones were predominant: CC235 (13.05%), CC244 (7.11%), CC654 (5.51%), and CC357 (4.21%). Three of these lineages – CC235, CC357, and CC654 – showed significantly higher levels of resistance to most antibiotics, including carbapenems, and were more frequently associated with nosocomial than communityacquired infections. Carbapenemase production was detected in 14.5% of isolates (VIM, 11.02%; GES-5, 2.61%; IMP, 0.44%; NDM, 0.44%), with the majority of carbapenemase-producing strains belonging to CC235 (52.0%) and CC654 (35.0%). WGS data revealed that CC235 isolates collected from different regions of Russia exhibited the greatest diversity of resistance determinants, including carbapenemase genes VIM-2, GES-5, and IMP-1. In contrast, all CC654 isolates carried the VIM-2 metallo-β-lactamase gene and shared similar genotypic and phenotypic resistance profiles to various antibiotic classes. Compared with previous surveillance data from the Russia, a decreasing trend was observed in the proportion of CC235 isolates, including carbapenemase producers, while the prevalence of other high-risk clones within the <em>P. aeruginosa</em> population remained stable.</p> <h3 id="conclusions">Conclusions.</h3> <p>Despite a decline in carbapenemase production frequency and overall carbapenem resistance, the data show that high-risk clones continue to serve as the main reservoirs and drivers of resistance dissemination, underscoring the importance of maintaining systematic molecular surveillance and control of their circulation.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p462/ Sat, 24 Jan 2026 13:29:26 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p462/ <h3 id="objective">Objective.</h3> <p>To study molecular and genetic features of <em>M. tuberculosis</em> (MTB) and human immunodeficiency virus (HIV) in patients with unfavorable course of HIV infection and tuberculosis.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 105 patients with HIV infection and newly diagnosed tuberculosis in whom tuberculosis was confirmed by microbiological and molecular genetic methods were included. The follow-up period was at least 6 months. Based on the results of the examination during treatment, all patients were divided into two groups: group 1 – patients with favorable course of HIV infection and tuberculosis (n = 78), group 2 – patients with unfavorable course of HIV infection and tuberculosis (n = 27). The study analyzed molecular and genetic features of HIV and MTB in patients with unfavorable/favorable course of HIV infection and tuberculosis.</p> <h3 id="results">Results.</h3> <p>In patients with an unfavorable course of HIV infection and tuberculosis (group 2), the frequency of detection of drug resistance mutations in the DNA of MTB was higher and the number of drugs to which mutations were present was greater than in patients with a favorable course of HIV infection and tuberculosis (group 1) (p = 0.030 and 0.019, respectively). The spectrum of drug resistance mutations was more diverse. Also, mutations of drug resistance to antiretroviral drugs (p = 0.042) were detected more often in HIV in group 2 patients, including to antiretroviral drugs of the non-nucleoside reverse transcriptase inhibitors and protease inhibitors classes, which pose high risk of antiretroviral therapy failure.</p> <h3 id="conclusions">Conclusions.</h3> <p>In patients with HIV/TB unfavorable course, both MTB and HIV studies are required to identify mutations of drug resistance and prescribe treatment regimens based on the resistance profile. The optimal solution is to determine resistance profile before starting HIV/TB treatment, which requires a powerful laboratory base.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p450/ Sat, 24 Jan 2026 13:27:28 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p450/ <h3 id="objective">Objective.</h3> <p>To assess impact of the COVID-19 pandemic on daily life and mental health of healthcare professionals in public medical institutions of the Russian Federation from their perspective and their attitude to the healthcare system’s response measures.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>From September to October 2024, as part of the qualitative data study, a semi-structured interview survey was conducted among 32 physicians and 18 nursing staff working during the COVID-19 pandemic in public outpatient and inpatient public medical institutions of the Russian Federation, repurposed or specially deployed to treat patients with COVID-19. The study was carried out in four cities located in various regions of the Russian Federation.</p> <h3 id="results">Results.</h3> <p>The participants described irregular and increased working hours due to a larger number of patients with a lack of medical personnel. This work overload harmed the emotional state of medical professionals, ranging from fatigue and anxiety to professional burnout and depression. An important aspect of the work that motivated healthcare professionals was the increase in their social value, however, this phenomenon was only temporary.</p> <h3 id="conclusions">Conclusions.</h3> <p>The data obtained can be useful for strategy development of ensuring labor safety in emergencies and, therefore, help reduce the negative impact of future challenges on the Russian healthcare system.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p442/ Sat, 24 Jan 2026 13:25:53 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p442/ <h3 id="objective">Objective.</h3> <p>To evaluate level of knowledge, attitudes, and practices (KAP) concerning sepsis and antimicrobial resistance (AMR) among medical students in the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A multicenter, cross-sectional survey was conducted among students from six medical universities using a validated questionnaire (Cronbach’s alpha: 0.74) developed based on the Knowledge, Attitudes, and Practices (KAP) model.</p> <h3 id="results">Results.</h3> <p>The study included 1052 respondents, comprising 315 (29.9%) males and 737 (70.1%) females, with a median age of 22 [21; 24] years. The primary sources of information on sepsis and AMR for students were academic curricula and the internet. A dissonance was identified between students’ self-assessed competence and their objective knowledge. Self-assessed competence in sepsis and AMR progressively increased with the year of study. Compared to the first year, the likelihood of positive self-assessment significantly increased in the third year (OR = 2.69; 95% CI: 1.35–5.46), fourth year (OR = 3.82; 1.83– 8.18), fifth year (OR = 4.40; 2.07–9.43), and sixth year (OR = 8.95; 4.17–19.86). Significant intercourse differences were found between the second and third (p = 0.03), third and sixth (p &lt; 0.001), and fourth and sixth (p = 0.01) years. The most substantial knowledge gaps were identified in awareness of modern diagnostic criteria for sepsis and the use of early warning scores (qSOFA and SOFA). Spearman’s correlation analysis revealed weak inter-domain correlations: between knowledge and attitudes (r = 0.19), knowledge and practices (r = 0.03), and attitudes and practices (r = 0.09). Possession of a prior secondary medical education did not have a significant effect on outcomes.</p> <h3 id="conclusions">Conclusions.</h3> <p>The findings demonstrate systemic deficiencies in medical students&rsquo; knowledge of sepsis and AMR. A notable disparity exists between high self-perceived competence and the actual level of knowledge. Knowledge, attitudes, and practices were found to be independent components in the development of a future physician, necessitating targeted educational interventions for each domain. The identified issues are of particular relevance, as sepsis and AMR represent critical global health challenges that impact all fields of clinical medicine and exert a substantial negative effect on patient outcomes.</p> http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p428/ Sat, 24 Jan 2026 13:13:58 +0000 http://cmac-journal.ru/en/publication/2025/4/cmac-2025-t27-n4-p428/ <h3 id="objective">Objective.</h3> <p>To study molecular biological features of Streptococcus agalactiae strains isolated from pregnant women and women in labor in various regions of the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 205 <em>S. agalactiae</em> strains isolated from pregnant women and women in labor in various regions of the Russian Federation for the period 2022–2023. The strains were isolated from vaginal rectal smears of pregnant women during screening at 35–37 weeks of gestation and from vaginal discharge of women in labor. Whole-genome sequencing data were obtained for each strain using high-throughput nucleotide sequencing. The bioinformatic analysis was carried out: genome assembly, multi-locus sequence typing (MLST), serotype determination of strains based on whole-genome sequencing data, detection of antimicrobial resistance genes, plasmid profile analysis, detection and analysis of mobile genetic elements.</p> <h3 id="results">Results.</h3> <p>The whole-genome sequencing data of 205 strains of <em>S. agalactiae</em> isolated from pregnant women, women in labor in various regions of the Russian Federation were obtained and their bioinformatic analysis was carried out. During serotyping, seven different serotypes were identified: Ia, Ib, II, III, IV, V, VI. Serotypes V (30.7%), III (28.3%), Ia (15.6%) were detected most often, serotypes II (9.8%), Ib (7.8%), IV (5.9%) and VI (1.9%) were less common. 28 different sequence types were identified, the following sequence types were most common: ST17 (14.6%), ST1 (12.7%), ST890 (11.2%), ST23 (7.3%), ST28 (5.9%), ST88 (5.4%), totaling more than 55% of all studied strains. The strains with sequence types belonging to five clonal complexes were most often identified: CC19 (18.5%), CC1 (17.1%), CC23 (16.1%), CC17 (15.1%) and CC452 (14.1%). Two different genes of resistance to aminoglycosides have been found in 51 strains – ant(6)-Ia, aph(3&rsquo;)-III; five genes of resistance to macrolides and/or lincosamides have been found in 119 strains – ermA, ermB, msrD, lsaC, mefA; two tetracycline resistance genes have been found in 188 strains – tetM and tetO and two chloramphenicol resistance genes have been found in 13 strains – cat, catQ, no vancomycin resistance genes have been found. Analyzing of the plasmid profile in <em>Streptococcus agalactiae</em> strains, one plasmid – repUS43 was identified, its incidence was 38.0%. 27 different types of mobile genetic elements with different frequencies were detected.</p> <h3 id="conclusions">Conclusions.</h3> <p><em>S. agalactiae</em> strains isolated from pregnant women and women in labor in various regions of the Russian Federation have different serotypes and sequence types occurring with different frequencies, and possess a spectrum of antimicrobial resistance genes and mobile genetic elements.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p417/ Fri, 31 Oct 2025 15:44:53 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p417/ <h3 id="objective">Objective.</h3> <p>To develop and conduct the first stage of validation for a PCR test that identifies key mutations in the V domain of the 23S rRNA gene of <em>M. pneumoniae</em> (A2058G, A2059G, and A2062C). This test allows for the identification of macrolide-resistant <em>M. pneumoniae</em> strains in samples of native biological material.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included a panel of <em>M. pneumoniae</em> DNA samples (n = 107) from the collection of the DeMaRes multicenter study, as well as native material (n = 52). This included oropharyngeal swabs (n = 45), tracheal aspiration (n = 4), and bronchial lavage (n = 3), which were obtained from March to April 2025 at G.N. Speranskiy Children Hospital No 9, Moscow. Nucleic acids were extracted from the native material using a RIBO-prep kit. The mutations in the 23S rRNA gene of <em>M. pneumoniae</em> was preliminarily determined using Sanger sequencing techniques and a modified PCR technique, which involved quenching fluorescence of the probe with primer. The concentration of control plasmids in order to determine the analytical sensitivity of the developed test was carried out using digital drip PCR.</p> <h3 id="results">Results.</h3> <p>The PCR test demonstrated 100% diagnostic sensitivity and specificity in detecting A2058G, A2059G, and A2062C mutations as well as wild-type <em>M. pneumoniae</em> DNA. Analytical sensitivity for all targets was 1 × 103 copies/ml. Among clinical samples with <em>M. pneumoniae</em> presence, the A2058G mutation prevailed at 35,7%, with A2059G and A2062C being less common. Results were consistent with sequencing data. The developed PCR test allows for the direct identification of the pathogen and <em>M. pneumoniae</em>&rsquo;s resistance markers to macrolides in biological material. The results demonstrate its high diagnostic capabilities and suggest that it will be successful in laboratory diagnostics.</p> <h3 id="conclusions">Conclusions.</h3> <p>xxx.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p406/ Fri, 31 Oct 2025 15:41:49 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p406/ <h3 id="objective">Objective.</h3> <p>Determination of the antimycobacterial efficacy of a composite material impregnated with silver in relation to <em>M. tuberculosis</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Samples of the outer shell of bulk porous composite materials with antimycobacterial substances included in the structure (silver (Ag) nanoparticles, as well as silver proteinate) were obtained at the Kurchatov Institute. In total, two types of samples with different particle contents were obtained: chitosan Ag and chitosan Ag2. To obtain an outer shell with an impregnated silver proteinate complex from chitosan Primex 43040 with glutaraldehyde: an aqueous solution of silver proteinate with different concentrations («chitosan Pr» and «chitosan Pr2») was added. The control sample was the outer shell without the addition of drugs. To determine the activity of composite material samples containing silver particles, a pure culture of the control strain <em>M. tuberculosis</em> H37Rv was used. The corresponding samples («chitosan Ag», «chitosan Ag2», «chitosan Pr» and «chitosan Pr2») and 100 µl of <em>M. tuberculosis</em> H37Rv suspension were added to the test tubes. The incubation duration is 28 days or upon reaching a growth control tube of 400 growth units.</p> <h3 id="results">Results.</h3> <p>The study was conducted on 2 concentrations of silver proteinate of 20 and 40 mg/ml, impregnated into chitosan implants and 2 concentrations of silver nanoparticles. In all cases, there was a growth retardation zone (7 mm), regardless of the concentration of the drug, i.e. antimycobacterial activity was weak. In tubes with chitosan implants without the active substance, the onset of growth was recorded on the 6th day, in tubes with chitosan implants impregnated with silver proteinate – on the 11th day, i.e. there is no complete suppression of culture growth. At high concentrations of silver nanoparticles (0.034–0.042 nmol/ml), complete inhibition of the growth of <em>M. tuberculosis</em> H37Rv was observed; at low concentrations, the culture growth point was on day 16. This composition is promising. Tubes with chitosan implants impregnated with silver nanoparticles in high concentration (0.034–0.042 nmol/ml) were left in the automated Bactec MGIT 960 system to assess the time interval of silver activity against <em>M. tuberculosis</em>, a positive result was recorded on the 35th day.</p> <h3 id="conclusions">Conclusions.</h3> <p>The study demonstrated antimycobacterial activity of various forms of silver. Silver proteinate requires a significant increase in concentration of impregnation in implants, which indicates a weak antimycobacterial activity of this drug, and silver nanoparticles at high concentrations (0.034–0.042 nmol/ml) show bactericidal activity against <em>M. tuberculosis</em> complex, lasting for 35 days.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p395/ Fri, 31 Oct 2025 15:39:09 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p395/ <h3 id="objective">Objective.</h3> <p>To assess impact of the COVID-19 pandemic on the structure of pathogens causing periprosthetic joint infection (PJI) and the dynamics of their antibiotic resistance.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective analysis of 379 strains of microorganisms isolated from patients with PJI of the knee and hip joints who underwent surgical treatment at the Federal Center for Traumatology and Orthopedics from 2018 to 2024 was performed. The biological material for the study was synovial fluid samples, tissue biopsies, aspirates from removed implants after ultrasonic treatment. Identification of the isolated pathogens and sensitivity to antibiotics were determined by the disk diffusion method and dilution methods on VITEC 2 compact or Multiscan FC analyzers in accordance with the EUCAST 2018, 2021, and 2024 criteria, depending on the year of study. Molecular methods were used to detect resistance genes.</p> <h3 id="results">Results.</h3> <p>The leading causative agents of PJI were gram-positive bacteria, the most common being CoNS in 27.7–46.7% and <em>S. aureus</em> in 23.4-33.0% of cases. In the post-COVID period, there was an increase in the frequency of gram-negative microorganisms from 6.5% to 14.9% (p = 0.0534) with a predominance of bacteria of the order <em>Enterobacterales</em> (p = 0.0242); an increase in the proportion of microbial associations from 4.3% to 11.8% (p = 0.0341) and the emergence of fungi. After the COVID-19 pandemic, an increase in methicillin-resistance was detected among coagulase-negative staphylococci (from 56.0% to 76.9%), the emergence of resistance to carbapenems and aztreonam among <em>Enterobacterales</em> and vancomycin among enterococci. Gram-positive bacteria were 100% sensitive to linezolid, and gramnegative bacteria were sensitive to colistin and tigecycline. Among the analyzed bacteria, high resistance to fluoroquinolones, co-trimoxazole and cefoxitin was detected (these drugs are not recommended for empirical therapy).</p> <h3 id="conclusions">Conclusions.</h3> <p>The impact of COVID-19 on the structure of PJI requires further study. Irrational use of antibiotics contributes to the emergence and growth of antibiotic resistance in pathogens of communityacquired infections and the development of the phenomenon of «parallel damage». This study highlights the need for continuous local monitoring of PJI pathogens and their antibiotic resistance to optimize treatment and prevention, including restrictive measures.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p390/ Fri, 31 Oct 2025 15:29:27 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p390/ <h3 id="objective">Objective.</h3> <p>To determine prevalence of <em>M. pneumoniae</em>, <em>C. pneumoniae</em> in patients with exacerbation of chronic obstructive pulmonary disease (COPD) in the autumn-winter period 2022–2023 in the Smolensk region.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study involved 53 patients with exacerbation of COPD who applied to the State Medical Institution «KB No. 1» in Smolensk for medical help. The clinical material for the study was a scrape from the posterior wall of the pharynx. DNA of the pathogen was detected using the AmpliSens® <em>Mycoplasma pneumoniae</em>/<em>Chlamydophila pneumoniae</em> FL kit (Central Research Institute of Epidemiology, Moscow, Russia).</p> <h3 id="results">Results.</h3> <p>The median age of the examined patients was 65 years (from 50 to 78), among them 12 women (21.2%), 41 men (78.8%). The proportion of patients with mild and moderate course was 54%, severe and extremely severe – 46%. M. pneumoniaе, <em>C. pneumoniae</em> were not detected in all the presented samples.</p> <h3 id="conclusions">Conclusions.</h3> <p>According to the clinical recommendations of the Ministry of Health of the Russian Federation for the management of COPD [1], the appointment of macrolides is indicated for exacerbation of the disease in patients with mild and moderate course without risk factors, as well as in long-term therapy is recommended for patients with frequent purulent exacerbations, regardless of severity. It should be noted that the widespread use of macrolides is limited by the risk of bacterial resistance to them and side effects (cardiotoxicity, hearing loss). In this regard, it is of interest to further study the prevalence of «atypical» pathogens in exacerbation of COPD, as well as the algorithm for the use of antibiotics in this group of patients.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p369/ Fri, 31 Oct 2025 15:26:40 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p369/ <h3 id="objective">Objective.</h3> <p>To implement a closed digital loop for continuous antimicrobial resistance (AMR) surveillance based on validated microbiological diagnostic results.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A prospective study was conducted at the Federal State Autonomous Institution «National Medical Research Center for Treatment and Rehabilitation» of the Ministry of Health of the Russian Federation from May 2024 to September 2025. An audit of the initial state of processes, a SWOT analysis, software restructuring, data flow optimization and standardization of diagnostic methods in accordance with EUCAST recommendations were performed. An integrated digital system was implemented, including a Laboratory Information System (LIS) with a microbiological module, a Microbiological Reference and Information System (MRIS) and a Medical Information System (MIS). The evaluation of the implementation effectiveness included a comparative analysis of key processes before and after the project, an epidemiological analysis of AMR surveillance data accumulated within the loop, as well as a survey of physicians (n = 47) regarding their work with the modified microbiological report.</p> <h3 id="results">Results.</h3> <p>The established digital loop ensured the automation and standardization of microbiological diagnostic processes from sample registration to final report generation. The implementation of the MRIS allowed for the automation of expert evaluation and validation of antimicrobial susceptibility testing (AST) reports, as well as ensuring a stable, continuous flow of a structured dataset, including metadata related to microbiological diagnostic data. A transition was achieved from manual, episodic AMR surveillance to continuous, real-time digital analysis. Data accumulated within the loop as part of AMR surveillance were analyzed. The possibility of a prospective approach to surveillance without the need for manual data curation was demonstrated. Multifactorial data analysis aimed at finding correlations between the resistance of key pathogens and risk factor metadata was demonstrated. The use of expert comments in the new validated AST report for optimizing antimicrobial therapy was illustrated with a clinical case. The physician survey showed that 91.5% of respondents found such comments useful for making decisions on optimizing antimicrobial therapy.</p> <h3 id="conclusions">Conclusions.</h3> <p>The project implementation successfully overcame systemic shortcomings related to data fragmentation and a high reliance on manual labor. The integrated digital loop transformed the microbiological service into a center of expertise and AMR data analytics, providing a reliable basis for the development and timely adjustment of local empirical antimicrobial therapy guidelines.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p359/ Fri, 31 Oct 2025 15:24:18 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p359/ <h3 id="objective">Objective.</h3> <p>To study the antimicrobial resistance and clonal diversity of vancomycin-resistant <em>E. faecium</em> in hematology.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Vancomycin-resistant <em>E. faecium</em> (VR-<em>E. faecium</em>) isolated from the blood culture of patients in six hospitals of Russia (2005–2023). Antimicrobial susceptibility of VR-<em>E. faecium</em> were determined by serial broth micro dilution was (CLSI, 2024), to tigecycline assessed according to EUCAST, 2025. Vancomycin-resistance genes (vanA, vanB) in VR-<em>E. faecium</em> were detected by multiplex PCR. Genotyping of VR-<em>E. faecium</em> was performed by MLST.</p> <h3 id="results">Results.</h3> <p>During the study period, 465 strains of <em>E. faecium</em> were isolated from blood culture, of which 122 (26.3%) were VR-<em>E. faecium</em>. The detection rate of VR-<em>E. faecium</em> increased from 13.1% (2005– 2011) to 59% (2018–2023, p = 0.0015). The majority of VR-<em>E. faecium</em> had the vanA genes (79.5%), while the vanB genes were detected in 20.5% of VR-<em>E. faecium</em>. All VR-<em>E. faecium</em> were susceptibledose dependent to daptomycin. The daptomycin MIC value of 4 μg/ml was determined in 16.4% of VR<em>E. faecium</em> and increased to 20.7% in 2018–2023. One (0.8%) VR-<em>E. faecium</em> strain was resistant to linezolid. All VR<em>E. faecium</em> isolates remained susceptible to tigecycline. A total of 24 sequence types (STs) belonging to clonal complex CC17 were detected. The predominant sequence types were ST80 (30.3%), ST17 (18.9%), and ST78 (13.1%). In 2023, a new ST2470 was registered in the pubMLST database. From 2018 to 2023, the proportion of ST80 increased to 62.1%, while ST17 and ST78 decreased to 13.8% and 5.2% respectively. vanA VR-<em>E. faecium</em> significantly more often belonged to ST80 (37.1% vs. 4%) and ST78 (15.5% vs. 4%) compared to vanB VR-<em>E. faecium</em>, which showed the predominance of ST17 (48% vs. 11.3%). VR<em>E. faecium</em> ST80 isolates exhibited significantly higher rates of daptomycin MICs of 4 μg/ml (21.6% vs. 8.7% and 6.2% for ST17 and ST78, respectively), and higher tetracycline resistance (64.9% vs. 4.3% and 6.3%) compared to ST17 and ST78. Streptomycin resistance was highest in ST78 (68.8%) compared to ST80 and ST17 (27% and 21.7% respectively).</p> <h3 id="conclusions">Conclusions.</h3> <p>In hematology, an increase in the frequency of VR-<em>E. faecium</em> was observed. Susceptibility to daptomycin, linezolid, and tigecycline was preserved among all studied VR-<em>E. faecium</em>. VR-<em>E. faecium</em> demonstrated significant clonal diversity and evolution during spread. Resistance profiles varied significantly among strains belonging to different STs.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p342/ Fri, 31 Oct 2025 15:21:27 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p342/ <h3 id="objective">Objective.</h3> <p>To study genetic determinants of resistance and virulence of <em>K. pneumoniae</em> strains received by the reference center for the prevention of the spread of biological threats of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 153 strains of <em>Klebsiella pneumoniae</em> isolated from the biological material of pregnant women and newborns in Perinatal centers in various regions of the Russian Federation with infectious and inflammatory diseases and included in the collection of opportunistic microorganisms of the reference center in 2023. For all strains, minimum inhibitory concentrations (MIC) to the main antimicrobials were determined by broth microdilution tests and whole-genome data were obtained using high-throughput sequencing technology. Bioinformatic analysis of whole-genome data, including genome assembly, multilocus sequence typing (MLST), strain typing by capsule and lipopolysaccharide loci, detection of the resistance and virulence genes, was performed. Strains with five (iucA, rmpA2, rmpA, peg344, terB) and more virulence genes combined in their genome were conditionally classified as hypervirulent. The hypermucoid phenotype in hypervirulent strains was detected using a string test.</p> <h3 id="results">Results.</h3> <p>All 153 strains of <em>K. pneumoniae</em> were searched for virulence genes. Virulence genes associated with the hypervirulent phenotype were not detected in 30 strains (19.6%) of <em>K. pneumoniae</em>. In 18 strains (11.8%), five or more virulence genes were combined in the genome, they were classified as hypervirulent. The remaining strains had a number of virulence genes ranging from 1 to 4. Sequence types of strains with different combinations of virulence genes were determined. For hypervirulent strains of <em>K. pneumoniae</em> capsule typing was performed, the spectrum of resistance to the main antimicrobials was determined, resistance genes of ten different groups were identified, and hypermucoid phenotype was detected in five strains.</p> <h3 id="conclusions">Conclusions.</h3> <p>The detection of multidrug-resistant hypervirulent <em>K. pneumoniae</em> strains in patients of Perinatal Centers, most of which belong to clones of high epidemic risk, indicates an increasing biological threat associated primarily with the horizontal transfer of plasmids with determinants of resistance and virulence, which makes it difficult to treat diseases caused by such bacteria.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p330/ Fri, 31 Oct 2025 15:19:29 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p330/ <h3 id="objective">Objective.</h3> <p>Development and validation of a suite of mathematical models to predict national-level antimicrobial resistance (AMR) trends by integrating antimicrobial consumption (AMC) and current AMR data.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Data on systemic antimicrobial consumption across 82 regions of the Russian Federation (2008–2022; source: IQVIA) and AMR levels (2013–2022; source: AMRmap.ru) were analyzed. The workflow included regional name normalization, exclusion of antimicrobials with low clinical relevance, calculation of moving averages (3–10 years) for AMR parameters, and AMC quantification in Defined Daily Doses (DDD). Principal Component Analysis (PCA) was applied for feature dimensionality reduction. Within the «model pair» framework (microorganism–antibiotic), machine learning algorithms were tested: LightGBM, Random Forest, logistic regression, and Support Vector Machines (SVM) with linear and Gaussian kernels. Hyperparameter optimization was performed via k-fold cross-validation, with model performance assessed using accuracy and recall metrics. AMR forecasting was conducted under two scenarios: optimized (COBYLA) and realistic (ETS model).</p> <h3 id="results">Results.</h3> <p>For the «<em>Escherichia coli</em> / cefotaxime» pair, the LightGBM model achieved the highest accuracy (67.5% training, 66.6% validation) without overfitting. Key predictors included historical AMR moving averages and infection type (community-acquired/hospital-acquired). Optimized consumption patterns projected a 15–20% reduction in AMR over a decade, whereas the realistic scenario predicted a 5–10% increase, particularly among community isolates. An online platform (AMCmodel.ru) was developed for data visualization, model access, and forecast generation.</p> <h3 id="conclusions">Conclusions.</h3> <p>The developed system enables accurate AMR trend forecasting and supports antimicrobial stewardship strategy design. Consumption optimization, as demonstrated by simulations, could reduce resistance by 15–20%. The AMCmodel.ru platform provides real-time decision-making tools. Further work will involve extending the suite of models to new microorganism-antibiotic pairs and incorporating international data to increase the predictive power of the models.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p317/ Fri, 31 Oct 2025 15:17:50 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p317/ <h3 id="objective">Objective.</h3> <p>To conduct a comparative <em>in vitro</em> analysis of the activity of biapenem and meropenem, as well as to evaluate the efficacy of their combinations with colistin against clinical isolates of <em>Klebsiella pneumoniae</em>, <em>Acinetobacter baumannii</em> and <em>Pseudomonas aeruginosa</em> producing carbapenemases of different molecular classes.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 197 carbapenem-resistant clinical isolates of <em>K. pneumoniae</em>, <em>A. baumannii</em> and <em>P. aeruginosa</em> with a phenotype of multidrug (MDR) and extensively drug (XDR) resistance. Antibiotic susceptibility was determined by the broth microdilution method in Mueller-Hinton broth according to the ISO 20776-1:2019 standard. To assess the effect of antibiotic combinations, a modified method for testing the bactericidal activity of various combinations (MCBT) and the checkerboard method with calculation of the fractional inhibitory concentration index (ΣFIC) were used. Molecular genetic characterization of the isolates was performed by polymerase chain reaction (PCR). PKPD analysis was performed using Monte Carlo simulations to predict the efficacy of two dosing regimens for biapenem.</p> <h3 id="results">Results.</h3> <p>Biapenem demonstrated statistically significantly lower MIC50 and MIC90 values compared to meropenem against the majority of the studied isolates. The greatest advantage of biapenem was revealed against NDM metallo-β-lactamase-producing <em>K. pneumoniae</em>: MIC50 was 2 mg/L versus 32 mg/L for meropenem. 74% of <em>K. pneumoniae</em> isolates were susceptible to colistin (MIC50/MIC90 – 0.¹²⁵&frasl;₆₄ mg/L). 98% of <em>P. aeruginosa</em> isolates also remained susceptible to colistin (MIC50/MIC90 – 0.¹²⁵&frasl;₀.125 mg/L), confirming its status as a «last-resort» antibiotic. The activity of biapenem/avibactam combinations against <em>P. aeruginosa</em> was observed only against clinical isolates that did not produce carbapenemases. Against <em>K. pneumoniae</em>, the activity of the biapenem (4 mg/L) + avibactam (4 mg/L) combination was highest against producers of a single type of carbapenemase (KPC – bactericidal effect against 69.2% of isolates, OXA48 – 88.5% of isolates, NDM – 83.3% of isolates); among co-producers of two types of carbapenemases, resistance to this combination was noted for 75% of isolates. For the vast majority of tested clinical isolates of <em>A. baumannii</em>, <em>P. aeruginosa</em>, and <em>K. pneumoniae</em>, combinations of carbapenems with colistin demonstrated a synergistic (ΣFIC ≤ 0.5) or additive (ΣFIC &gt; 0.5 and ≤ 1.0) effect. Combinations of both carbapenems with colistin exhibited bactericidal activity against most isolates. Quantitative analysis by the checkerboard method revealed that the biapenem + colistin combination has an advantage over the meropenem + colistin combination against NDM-producing <em>K. pneumoniae</em> isolates (FIC50 1 mg/L and 8 mg/L, respectively). For the dosage regimen of biapenem 1000 mg/8h administered as a 3-hour infusion, efficacy has been predicted for strains with a MIC of ≤4 mg/L.</p> <h3 id="conclusions">Conclusions.</h3> <p>Biapenem exhibits a statistically significant higher <em>in vitro</em> activity than meropenem against meropenem-resistant clinical isolates of <em>K. pneumoniae</em>, <em>A. baumannii</em>, and <em>P. aeruginosa</em> with multidrug and extensive drug resistance, isolated in the Republic of Belarus. The combination of biapenem with colistin demonstrates high efficacy and synergy against multidrug-resistant isolates, making it a promising option for empirical and targeted therapy of severe infections caused by these pathogens, especially in regions with a high prevalence of MBL-producing isolates.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p309/ Fri, 31 Oct 2025 15:15:32 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p309/ <h3 id="objective">Objective.</h3> <p>To determine frequency and spectrum of cytomegalovirus (CMV) resistance mutations to antiviral drugs in immunocompromised children. To study clinical course of resistant CMV infection in this patient population.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>This prospective study included 120 patients of the Dmitry Rogachev NMRC PHOI who mainly were recipients of allogeneic hematopoietic stem cell transplantation (HSCT) with confirmed CMV infection (median age – 8.9 years). The study inclusion criterion was the possible development of CMV drug resistance. With an increase in the CMV blood viral load (determined by real-time polymerase chain reaction), UL97 and UL54 genes mutations associated with CMV resistance to antiviral drugs (using Sanger sequencing) were studied.</p> <h3 id="results">Results.</h3> <p>Of 120 patients, 27 (22.5%) were found to have resistant CMV strains. The following mutations and their combinations were identified in CMV pUL97 protein kinase: A594V (n = 8), L595S (n = 6), H520Q (n = 2), A591V (n = 1), C592G (n = 1), C592S (n = 1), C607F (n = 1), C607Y (n = 1), C603W (n = 1), A594V/H520Q (n = 2), L595F/C592G (n = 1), L595S/M460V (n = 1); in the DNA polymerase pUL54: N408D (n = 1), V715H (n = 1), V781I/K513R (n = 1), L773V (n = 1). The most common mutations were A594V (37%) and L595S (27%). The median time from the start of antiviral therapy to the detection of a resistance mutation was 108 days (11-306 days). The following features were recorded in patients with CMV resistance mutations: higher values of peak viral load in the blood (p = 0.005), longer viral elimination (p = 0.001), and more frequent development of invasive fungal infections (p = 0.001). The overall survival rate in this group of patients was 60% versus 79% in patients without resistance mutations (p = 0.074).</p> <h3 id="conclusions">Conclusions.</h3> <p>Frequency and spectrum of mutations responsible for CMV drug resistance in immunocompromised children have been determined. The most common mechanisms of CMV resistance to ganciclovir were A594V and L595S mutations of protein kinase pUL97. pUL54 mutations were detected less frequently and represented by the following: N408D, V781I, V715H and L773V. It is necessary to emphasize the importance of timely detection of resistant strains and adjustment of treatment strategy due to a more severe course of the disease when CMV resistance mutations are presented: longer viral persistence, increased incidence of fungal infections, decreased overall survival.</p> http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p268/ Fri, 31 Oct 2025 14:58:42 +0000 http://cmac-journal.ru/en/publication/2025/3/cmac-2025-t27-n3-p268/ <h3 id="objective">Objective.</h3> <p>To investigate the genetic diversity of the Russian population of <em>C. trachomatis</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We analyzed 42 clinical isolates of <em>C. trachomatis</em> obtained in 2024. MLST typing was performed using the Uppsala scheme (genes CT058, CT144, CT172, hctB, pbpB) and sequencing of the ompA gene for serotype determination.</p> <h3 id="results">Results.</h3> <p>8 serotypes (E – 50.0% predominates) and 26 sequence types (ST) were identified, including 8 new ones (19.0% of isolates). The prevailing ST56 (33.3%) differs from global trends (ST3). A rare serotype B (trachoma) was found in urogenital samples, which may indicate recombination between biovars.</p> <h3 id="conclusions">Conclusions.</h3> <p>The revealed significant genetic diversity of <em>C. trachomatis</em> strains circulating in Russia, with the dominance of serotype E (50.0%) and sequence type ST56 (33.3%), is partially consistent with global trends, but has important regional differences. The absence of ST3, which is widespread in other countries, and the identification of 8 new STs (19.0% of isolates) highlight unique features of the Russian pathogen population. The detection of serotype B (trachoma) in urogenital samples confirms the possibility of recombination between different biovars and the need to track cross-border drifts of the pathogen. The data obtained indicate the necessity to expand the study of the genetic diversity of chlamydia in Russia and emphasize the importance of standardizing molecular typing methods. Further studies with a larger sample size from different regions of Russia will make it possible to clarify the identified patterns and mechanisms of genetic variability of the pathogen, as well as to assess the impact of migration processes on the population structure.</p> http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p258/ Sat, 23 Aug 2025 15:37:13 +0000 http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p258/ <h3 id="objective">Objective.</h3> <p>To compare antibacterial activity of macrocidins A and Z against staphylococci and their effect on staphylococcal biofilms.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The antibacterial activity of macrocidins A and Z produced by Didymella baileyae VIZR 1.53 was studied by serial dilution method against 120 staphylococcal cultures isolated from orthopedic patients. The effect of macrocidins on biofilm formation of 60 <em>S. aureus</em> clinical cultures was assessed by O&rsquo;Toole method by co-incubation of active substances with bacteria and subsequent MBIC50/90. The impact on the formed biofilms was assessed after treating the formed staphylococcal biofilms with different concentrations of macrocidins using MBEC50/90 calculation. Statistical analysis was performed in GraphPad Prism 9.0.</p> <h3 id="results">Results.</h3> <p>The MIC50/90 macrocidin A against <em>S. aureus</em> – 256 mg/L, MIC50/90 of macrocidin Z – ²⁵⁶&frasl;₂₅₆ mg/L. Macrocidin Z was found to be more active against <em>S. epidermidis</em> than against <em>S. aureus</em> (MIC50/90 ¹²⁸&frasl;₁₂₈ mg/L). Comparison of the susceptibility of methicillin-sensitive and methicillin-resistant <em>S. aureus</em> and <em>S. epidermidis</em> did not reveal any differences in the MIC50/90 of macrocidins, indicating sensitivity to the compounds regardless of their antibiotic susceptibility. A pronounced inhibitory effect of macrocidins on biofilm formation by <em>S. aureus</em> was established, more pronounced for macrocidin Z, as well as differences in the effect of macrocidins on biofilms depending on the antibiotic susceptibility of the strains. It was shown that macrocidins in the tested concentrations (8–256 mg/l) did not have a destructive effect, regardless of their antibiotic sensitivity profile.</p> <h3 id="conclusions">Conclusions.</h3> <p>Macrocidins A and Z significantly inhibited the growth of <em>S. aureus</em> and <em>S. epidermidis</em>. The ability to suppress biofilm formation at low concentrations is also of interest, especially for the possible use of macrocidins as antibacterial and antiadhesive compounds.</p> http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p238/ Sat, 23 Aug 2025 15:33:26 +0000 http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p238/ <h3 id="objective">Objective.</h3> <p>To analyze physicians’ preferences regarding the pharmacotherapy of bacterial genitourinary infections (UTI) in pregnant women and assess their compliance with current clinical guidelines.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study was conducted over 2018–2022 using an anonymous questionnaire method among physicians in seven regions of Russia. A total of 227 healthcare providers participated, of whom 66.8% were general practitioners and 33.2% were obstetricians/gynecologists.</p> <h3 id="results">Results.</h3> <p>According to the analysis, there is an insufficient level of knowledge in the field of pharmacotherapy of UTIs in pregnant women. The respondents showed the best results in the treatment of chlamydia: in 79.9% of the questionnaires the correct tactics were chosen. The worst results were observed in the issues of detection and treatment of β(beta)-hemolytic streptococcus (BHSV) carriage: in 46.8% and 56.8% of questionnaires, respectively, the wrong tactic was chosen.</p> <h3 id="conclusions">Conclusions.</h3> <p>The results of this study showed a low level of knowledge in the field of UTI therapy in different regions, as well as some discrepancies in the issues of pharmacotherapy according to domestic clinical guidelines. The differences are significant in some centers, which may indicate heterogeneity of knowledge in different regions. It is especially important to note that some specialists prescribe antimicrobials characterized by their unsafety for pregnant women and fetus.</p> http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p217/ Sat, 23 Aug 2025 15:28:47 +0000 http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p217/ <h3 id="objective">Objective.</h3> <p>To study susceptibility of clinical Bacteroides spp. and Clostridium perfringens isolates to antimicrobial agents across different regions of the Russian Federation and to identify regional patterns of antimicrobial resistance.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 1,685 isolates of obligate anaerobic bacteria belonging to 107 species, isolated from patients in 60 regions of the Russian Federation during period from January 2023 to December 2024. Among them, 144 C. perfringens isolates from 37 regions, and 370 Bacteroides spp. isolates from 53 regions. Identification was performed using the MALDI-TOF MS method, antimicrobial susceptibility testing was conducted using the disk diffusion method and agar dilution method in accordance with the Russian guidelines &laquo;Determination of Microorganism Susceptibility to Antimicrobial Agents,&raquo; version 2024-02.</p> <h3 id="results">Results.</h3> <p>Significant variability in resistance levels was observed across different regions. Among Bacteroides spp. high resistance rates was detected for meropenem (48.92%), metronidazole (34.59%), and piperacillin-tazobactam (38.38%). C. perfringens demonstrated high susceptibility to vancomycin (93.75%) but considerable resistance to clindamycin (47.92%). Isolates of Bacteroides spp. exhibiting complete resistance to all tested antibiotics were found in 14 regions, while multidrug-resistant C. perfringens strains were identified in 7 regions.</p> <h3 id="conclusions">Conclusions.</h3> <p>This study confirms a significant prevalence of antibiotic resistance among anaerobic microorganisms in Russian hospitals. Marked regional differences in resistance patterns emphasize the need for enhanced monitoring and the development of region-specific antimicrobial therapy strategies.</p> http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p206/ Sat, 23 Aug 2025 15:26:34 +0000 http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p206/ <h3 id="objective">Objective.</h3> <p>Comparative assessment of <em>in vitro</em> susceptibility of <em>M. avium</em> isolated from patients with mycobacteriosis (MB) with positive and negative HIV status.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p><em>M. avium</em> isolates of were revealed during 2018–2023 from clinical samples of 402 adult patients (≥ 18 years old) in the National Medical Research Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation: 144 strains were isolated from individuals with HIV infection (HIV+) and 258 – from patients with a negative HIV status (HIV-). Susceptibility was determined for 15 antimicrobials: amikacin, clarithromycin, rifabutin, rifampin, ethambutol, streptomycin, ciprofloxacin, doxycycline, isoniazid, ethionamide, linezolid, moxifloxacin, trimethoprim-sulfamethoxazole, bedaquiline, reviewed using the broth microdilution method in accordance with the CLSI M24-A2, 2018 guidelines. Antimicrobial susceptibility categories were determined based on minimum inhibitory concentration (MIC) breakpoints according to CLSI M24S, 2023 standards. For amikacin, clarithromycin, linezolid, and moxifloxacin, <em>M. avium</em> complex breakpoints were used. For ciprofloxacin, doxycycline, rifabutin, and rifampin, MIC breakpoints for other slow-growing NTMs (M. kansasii and M. marinum) according to CLSI M24S, 2023 Non-Species Breakpoints were used. For ethambutol, isoniazid, streptomycin, ethionamide, bedaquiline, delamanid, MIC breakpoints for slowgrowing NTM have not been established. Quality control is performed using <em>M. avium</em> strain ATCC 700898.</p> <h3 id="results">Results.</h3> <p>The highest susceptibility level (&gt; 60%) of <em>M. avium</em> in patients with MB HIV+ and MB HIV- was observed to rifabutin (94.4% and 87.6%), amikacin (78.5% and 72.1%), clarithromycin (75.7% and 64.7%); relatively low susceptibility level (60–40%) – to moxifloxacin (56.9% and 50.4%), trimethoprimsulfamethoxazole (43.6% and 52.9%); the lowest susceptibility level (&lt; 40%) – to doxycycline (2.1% and 0.4%), linezolid (14.6% and 14.7%), ciprofloxacin (14.6% and 15.5%), rifampicin (34.0% and 36.4%). Statistically significant higher susceptibility was noted for the isolates from patients with MB HIV+ than in patients with MB HIV- to: rifabutin (94.4% versus 87.6%, p = 0.04), clarithromycin (72.1% vs. 64.7%, p = 0.03). There were more resistant isolates in patients with MB HIV- than in MB HIV+ to: rifabutin (12.4% vs. 5.6%, p = 0.04), clarithromycin (19.8% vs. 9.7%, p = 0.01), moxifloxacin (29.1% vs. 18.8%, p = 0.03). More isolates with intermediate susceptibility to amikacin were detected in the group of patients with MB HIV- than with MB HIV+ (6.3% vs. 18.6%, p = 0.001). In addition, higher MIC50 values were observed for <em>M. avium</em> isolates from HIV- MB patients than from HIV+ MB for: amikacin (16 μg/mL vs. 8 μg/mL), clarithromycin (8 μg/mL vs. 4 μg/mL), isoniazid (16 μg/mL vs. 8 μg/mL), streptomycin (32 μg/ mL vs. 16 μg/mL). Higher MIC90 values were also observed against <em>M. avium</em> isolates from MB HIV- than MB HIV+ patients for: rifabutin (4 μg/ml vs. 2 μg/ml), amikacin (32 μg/ml vs. 16 μg/ml), clarithromycin (32 μg/ml vs. 16 μg/ml), moxifloxacin (8 μg/ml vs. 4 μg/ml), doxycycline (256 μg/ml vs. 128 μg/ml), rifampin (32 μg/ml vs. 16 μg/ml), delamanid (2 μg/ml vs. 1 μg/ml), isoniazid (128 μg/ml vs. 32 μg/ml), streptomycin (128 μg/ml vs. 64 μg/ml).</p> <h3 id="conclusions">Conclusions.</h3> <p>The level of <em>in vitro</em> activity of 9 of 15 antimicrobials (clarithromycin, rifampicin, rifabutin, amikacin, streptomycin, moxifloxacin, doxycycline, isoniazid, delamanid) was lower for <em>M. avium</em> isolates from MB HIV- patients than for isolates from MB HIV+ patients. These results were confirmed by statistically significant differences in the number of susceptible, moderately susceptible and resistant isolates and/or MIC50 and/or MIC90 values, which were higher in the MB HIV- group than in the MB HIV+ group. At the same time, the level of activity of none of the 15 studied antimicrobials against <em>M. avium</em> isolates from MB HIV+ patients was lower than those from MB HIV- patients.</p> http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p134/ Sat, 23 Aug 2025 15:11:40 +0000 http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p134/ <h3 id="objective">Objective.</h3> <p>To characterize spectrum of <em>S. pneumoniae</em> serotypes isolated from patients with invasive pneumococcal infection in the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The serotype identification of 93 <em>S. pneumoniae</em> isolates obtained from blood and cerebrospinal fluid of patients with various forms of invasive pneumococcal disease was performed using whole-genome sequencing. PCV-13, PCV-15, PCV-20 and PPV-23 coverage of circulated serotypes was estimated using descriptive statistics.</p> <h3 id="results">Results.</h3> <p>The study included 93 <em>S. pneumoniae</em> isolates obtained from blood and cerebrospinal fluid of patients diagnosed with bacterial meningitis (n = 66, 65.6%), pneumonia (n = 19, 25.8%), bacteremia (n = 7, 7.5%), and infectious endocarditis (n = 1, 1.1%). The most frequent <em>S. pneumoniae</em> serotypes responsible for the development of invasive pneumococcal infections in this study were: 3 (n = 15, 16.1%), 19F (n = 6, 6.5%), 9N, 18C, and 23A (n = 5, 5.4%), 8, 14, 17F, and 20 (n = 4, 4.3%), 4, 5, 23F, and 28A (n = 3, 3.2%). Vaccine coverage analysis showed that PCV-13 covers 48.4% (CI 38.2%– 58.6%) of the identified <em>S. pneumoniae</em> serotypes, PCV-15 – 49.5% (CI 39.3%–59.7%), PCV-20 – 57.0% (CI 46.9%–67.1%), and PPSV-23 – 71.0% (CI 61.8%–80.2%).</p> <h3 id="conclusions">Conclusions.</h3> <p>The analysis of the spectrum of <em>S. pneumoniae</em> serotypes isolated from patients with invasive pneumococcal infections revealed a wide diversity. Serotypes included in PCV-13, which is part of the National Immunization Schedule of the Russian Federation, were identified in only 48.4% of cases.</p> http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p124/ Sat, 23 Aug 2025 15:07:32 +0000 http://cmac-journal.ru/en/publication/2025/2/cmac-2025-t27-n2-p124/ <h3 id="objective">Objective.</h3> <p>To assess prevalence, etiology, antimicrobial prescribing practices and treatment outcomes of infections in intensive care units in Russia.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A two-stage (the first stage – October 18, 2022, the second stage – November 18, 2022) multicenter prospective one-day observational study involved 111 intensive care units (ICUs) of 67 centers from 25 cities of the Russian Federation. Each patient was included in the study only once. Data from the medical records of all patients in the ICU on the day of the study were entered by the attending physician into a single electronic individual case report form. Patients were monitored throughout their hospital stay until transfer from the ICU and discharge from the hospital.</p> <h3 id="results">Results.</h3> <p>The study included data on 1274 patients, of whom 896 (70.3%) had signs of infection (in 73% of cases, the infection was associated with healthcare – HAI). The most common localization of infection was the respiratory system (32.6%), abdominal cavity (13.6%) and skin/soft tissues (9.6%); in 17.6% of cases, the source of infection was not identified. Among patients with HAI, 29.2% developed sepsis, and 10.4% developed septic shock. Artificial ventilation was an independent risk factor for respiratory infections (OR = 3.06 [95% CI 2.35–3.99]; p &lt; 0.001), the presence of a urinary catheter was a risk factor for urinary tract infections (OR = 4.54 [95% CI 1.41 – 14.65]; p = 0.006). Mortality in patients with infection was 24.7%, while according to the treating physicians, 52.9% of patients died directly from infectious causes. The SOFA index had a significant impact on mortality (OR = 1.25; 95% CI 1.17–1.33; p &lt; 0.001). Mortality was higher among patients admitted for emergency indications and among surgical patients. The presence of a localized infection increased the risk of death by 1.5 times, sepsis – by 1.8 times. Gram-negative bacteria were the leading causative agents of infections (67.4% of all cases, 74.4% in the structure of bacterial pathogens); Gram-positive bacteria in the general etiological structure accounted for 23.3%. The three most common pathogens were <em>Klebsiella pneumoniae</em> (26.7%), <em>Acinetobacter baumannii</em> (15.3%) and <em>Pseudomonas aeruginosa</em> (10%). Microorganisms that are not characteristic of the corresponding loci of infection were often indicated as causative agents, so 13.5% of all microorganisms reported in respiratory infections were <em>Candida</em> spp., coagulase-negative staphylococci, enterococci and non-diphtheria corynebacteria. In total, antimicrobial drugs were prescribed to 56.1% of patients in monoand combination therapy regimens. The most frequently prescribed drugs were cephalosporins (all – 24.6%, cephalosporins III – 7.8%, ceftazidime/avibactam – 1.4%) and carbapenems (23.1%). The frequency of prescribing glycopeptides was 8.1%, inhibitor-protected penicillins – 7.7%, aminoglycosides – 6.4%, fluoroquinolones – 6.2%, polymyxins – 5.1%, oxazolidinones – 4.1%, metronidazole – 3.5%, tigecycline – 3.3%, antifungal drugs – 2%.</p> <h3 id="conclusions">Conclusions.</h3> <p>The study demonstrates a high proportion of patients with infections in the intensive care units of Russia, the majority of which are nosocomial infections. The etiological structure of infectious agents reflects the global trend of the spread of poly- and extremely resistant Gram-negative microorganisms. The structure of the prescribed antimicrobial therapy does not fully correspond to the profile of pathogens and their resistance. The data obtained indicate the need for measures to strengthen epidemiological surveillance, implement and monitor adequate infection control protocols, revise the practice of microbiological diagnostics and develop algorithms for prescribing antimicrobial drugs based on local resistance monitoring data.</p> http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p111/ Sat, 10 May 2025 13:50:27 +0000 http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p111/ <h3 id="objective">Objective.</h3> <p>To study the characteristics of microbial landscape in patients with chronic obstructive pulmonary disease and chronic simple bronchitis of occupational etiology from mineral dust exposure (COPD OE) with different clinical phenotypes.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Patients were divided into 3 groups. Group-1 – 10 patients with COPD OE, clinical phenotype “B” (GOLD II); Group-2 – 19 patients with COPD OE, clinical phenotype “E” (GOLD III-IV); Group-3 – 11 patients with chronic simple bronchitis (CSBPE). Clinical samples were inoculated on solid nutrient media; the culture was incubated under aerobic and microaerophilic conditions. The identification of grown cultures was carried out using the MALDI-ToF mass spectrometry. Antimicrobial susceptibility was determined by disk diffusion method.</p> <h3 id="results">Results.</h3> <p>The common characteristics of the microbiota in COPD patients with both phenotypes were: the predominance of the Firmicutes type, equal bacterial load (p = 0.48), the absence of protective commensals and microorganisms typical for COPD patients (<em>Moraxella catarrhalis</em>). <em>Streptococcus pneumoniae</em> and Hemophilus influenzae were found in only one patient (phenotype “E”). The COPD OE phenotype “E” was qualitatively different from the phenotype “B” due to the predominance of Pseudomonadota (p = 0.0005), potentially pathogenic microorganisms over non-pathogenic microorganisms (54% versus 19%, p = 0.0005), lesser quantity of Neisseriales, more antibiotic-resistant microorganisms and more <em>Candida</em> spp.</p> <h3 id="conclusions">Conclusions.</h3> <p>The study results may indicate significant heterogeneity of the microbiota in patients with occupational COPD due to exposure to mineral dust. The common features of all phenotypes were the tendency to growth of opportunistic microbiota, presence of antibiotic-resistant isolates. Patients with frequent exacerbations had T2 endotype of inflammation, they showed more pronounced simplification of microbiota, growth of opportunistic microbiota resistant to antibiotics. Disturbances in the microbiota in patients with CPB PE indicate the involvement of microorganisms in the processes of inflammation and remodeling of airways at an early stage of the disease, which requires further research. The obtained results should be taken into account when conducting empirical antibacterial therapy of exacerbations in these patients, as well as the inclusion of vaccine prophylaxis against pneumococcus in the rehabilitation program of COPD PE and CPB PE patients</p> http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p101/ Sat, 10 May 2025 13:48:28 +0000 http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p101/ <h3 id="objective">Objective.</h3> <p>To analyze antimicrobial susceptibility of representatives of the genus Streptococcus in different wards of a multidisciplinary hospital.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Epidemiological observational descriptive continuous retrospective survey was conducted. Antimicrobial susceptibility data on 2916 streptococcal isolates obtained from the laboratory information system «ALISA» were analyzed for the period from 01.01.2017 to 31.12.2022. Antimicrobial susceptibility testing was performed using BD Phoenix M50, interpretation of susceptibility testing results was done in accordance with EUCAST recommendations. Statistical analysis was performed using Microsoft Excel 2010 and IBM SPSS Statistics22.</p> <h3 id="results">Results.</h3> <p>The following species of the genus Streptococcus were predominantly isolated: in the surgical infections ward – <em>S. pyogenes</em> (28.5%), S. agalactiae (22.0%), S. anginosus (16.5%); in the coloproctology ward – S. anginosus (41.7%), S. constellatus (16.0%), S. agalactiae (14.5%); in the surgical ward – S. anginosus (40.1%), S. constellatus (31.4%); in the intensive care ward – S. anginosus (21.8%), S. constellatus (11.3%), S. oralis (11.1%); in the gynecology ward – S. agalactiae (49.9%) and S. anginosus (31.3%). Significant proportion of S. agalactiae isolates were resistant to tetracycline and clindamycin in all wards. There was an increase in S. agalactiae resistance to erythromycin from 15.4% in 2019 to 38.3% in 2021 in the surgical infections ward, and from 16.7% to 38.5% – in the coloproctology ward. In addition, resistance to clindamycin increased from 24.2% in 2018 to 71.3% in 2020 to in surgical infections ward, from 13.6% to 70.7% in coloproctology ward, and from 20.0% to 90.3% in gynecology ward. In the intensive care unit, S. agalactiae and <em>S. pyogenes</em> were most frequently resistant to tetracycline (79.5% and 51.3%), erythromycin (32.8% and 31.7%) and trimethoprim-sulfamethoxazole (18.5% and 26.8%, respectively). <em>S. pneumoniae</em> showed the highest level of resistance to erythromycin (35.3%), clindamycin (29.3%) and trimethoprim-sulfamethoxazole (26,0%).</p> <h3 id="conclusions">Conclusions.</h3> <p>In recent years, an increase in antimicrobial resistance has been identified in the most common streptococci. The antibiotic susceptibility of streptococci of the same species was found to be variable in different hospital wards. There was a tendency noted for increase in the occurrence of multiresistant strains of <em>S. pyogenes</em> and S. agalactiae in the intensive care and surgical infections ward.</p> http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p94/ Sat, 10 May 2025 13:46:28 +0000 http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p94/ <h3 id="objective">Objective.</h3> <p>To study the microbial composition of biopsies in inflammatory bowel diseases.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>From November 2019 to February 2023, 100 patients of the coloproctology department with inflammatory bowel diseases (IBD) were examined: 65 patients with ulcerative colitis and 35 patients with Crohn&rsquo;s disease. A metagenomic analysis of biopsies (DNA sequencer Illumina, USA) obtained during endoscopic examination using a standard technique, with a bioiformatic data analysis, was performed. The diversity of microbiomes in the samples was assessed using the Fisher index. The similarity of microbiomes between samples (beta diversity) was estimated using the Bray–Curtis distance. The analysis of the main coordinates (PCoA) was performed to visualize the similarity of microbiomes between samples. The results were considered statistically significant at p &lt; 0.05.</p> <h3 id="results">Results.</h3> <p>Metagenomic analysis made it possible to study the qualitative and quantitative composition of the intestinal microbiota in patients with ulcerative colitis and Crohn&rsquo;s disease. 20 types of microorganisms were identified, including 146 families, 336 genera, 516 species of microorganisms. At the phylum level, two main ones were obtained: Proteobacteria, Firmicutes. Comparing the studied nosological forms with each other, there is an increase in the diversity of bacteria of the phylum Proteobacteria by 1.2 times in ulcerative colitis. The predominant species of this phylum is <em>Escherichia coli</em>. In turn, the relative abundance of <em>E. coli</em> is 1.6 times higher in patients with Crohn&rsquo;s disease (23.9%/14.48%). Taxonomic categories that are absent in this or that type of disease have been identified – departments: Cyanobacteria (0.049%), Acidobacteria (0.010), Planctomycetes (0.009%), SR1 (0.007%), Synergistetes (0.007%), Chloroflexi (0.004%), Lentisphaerae (0.002%), OD1 (Parcubacteria) (0.001%), Spirochaetes (0.001%), Helicobacter genus (5%) were detected only in patients with ulcerative colitis; department Gemmatimonadetes (0.009%) – with Crohn&rsquo;s disease.</p> <h3 id="conclusions">Conclusions.</h3> <p>Identification of intestinal microorganisms associated with the pathogenesis of inflammatory bowel diseases is a critical aspect for a thorough understanding of the various pathogenic factors that are of great importance for the early detection of IBD.</p> http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p88/ Sat, 10 May 2025 13:45:04 +0000 http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p88/ <h3 id="objective">Objective.</h3> <p>To describe the phenotypic and genome characteristics of the phenomenon of aztreonam susceptibility changes in a clinical <em>Pseudomonas aeruginosa</em> isolate developing colistin resistance in an evolutionary experiment <em>in vivo</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A clinical <em>P. aeruginosa</em> isolate with a multiple drug resistance phenotype was examined using the spaciotemporal model of colistin resistance development under the increasing colistin concentration. During the 44-day experiment, isolates were selected from the frontal growing line; these isolates were subjected to antimicrobial susceptibility testing and genome sequencing.</p> <h3 id="results">Results.</h3> <p>An aztreonam MIC of the parental isolate was 4 mg/L corresponding to the EUCAST category ‘susceptible, increased exposure’. Among the 74 selected <em>P. aeruginosa</em> isolates, 11 isolates changed the aztreonam MIC. Six out of 11 isolates became more susceptible to aztreonam, whereas in the remaining 5 isolates the aztreonam MIC increased. Isolates with the restored aztreonam susceptibility carried alterations in pmrB (del-18bp-298-315) and davD (TGA1450-1452→CTC). In isolates with a 4-fold aztreonam MIC elevation, various mutation profiles were observed. An isolate with a maximal aztreonam elevation of 32 mg/L harbored a capD mutation (del-T-360) and a large 262,402 bp deletion (239 ORF). Mutations in phoQ, lpxL_2, wecA, mexB, spaQ, pcpR and rpoA did not influence the susceptibility to aztreonam.</p> <h3 id="conclusions">Conclusions.</h3> <p>Our results contributed to the understanding of the directions of genetic engineering modeling aimed at expanding the understanding of the mechanisms of resistance to aztreonam.</p> http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p73/ Sat, 10 May 2025 13:42:34 +0000 http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p73/ <h3 id="objective">Objective.</h3> <p>To determine molecular biological characteristics of <em>Candida albicans</em> strains from patients with recurrent vulvovaginal candidiasis (RVVC) associated with the formation of resistance to azole drugs.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 36 clinical isolates of <em>C. albicans</em> from patients with RVVC who sought outpatient care at the P.N. Kashkin Research Institute of Medical Mycology from July to November 2024. Species identification of <em>Candida</em> spp. was performed using MALDI-TOF mass-spectrometry and targeted sequencing. The susceptibility of <em>Candida</em> spp. to antifungal drugs (AFDs) was determined using the Fungus AST test system (Autobio Diagnostics Co, China) with the interpretation of MIC clinical breakpoint values in accordance with CLSI M27A, 2022. The nucleotide sequence of the ERG11 gene was studied using targeted sequencing on an ABI PRISM 3500 genetic analyzer. The expression level of genes encoding drug transporter proteins CDR1, CDR2, MDR1 and FLU1 was analyzed by real-time PCR using the fluorescent dye EVA Green using the relative 2-∆∆Сt measurement method. Biofilm formation of <em>C. albicans</em> strains was assessed by total cell mass (staining with an aqueous solution of crystal violet) and metabolic activity of cells (tetrazolium salt reduction method). Statistical processing of the results was carried out using nonparametric evaluation criteria of the SPSS v.22.0.</p> <h3 id="results">Results.</h3> <p>11 (30.5%) strains were susceptible to fluconazole, 6 (14.0%) classified as “susceptible dosesensitive”, 20 (55.5%) were resistant to this AFD. All strains were susceptible to polyenes, echinocandins and 5-flucytosine. The work shows a correlation between the nucleotide polymorphism of the ERG11 gene and the sensitivity of the strain to fluconazole. Resistant strains of <em>C. albicans</em> (MIC &gt; 8 mg/l) were characterized by the lowest variability and the presence in the genotype of a single missense mutation T394C (Y132H), associated with resistance to azoles. A possible role of A1343G (E448G) as a suppressor intragenic mutation that neutralizes the effect of T394C (Y132H) on conformational changes in the Erg11 protein has been suggested. Further research is need in this aspect. The ERG11 and FLU1 genes showed increased expression levels (р = 0.004 and р = 0.012, respectively) in fluconazole-resistant <em>C. albicans</em> strains compared to susceptible strains. No significant differences were found in the expression of genes encoding drug transporter proteins CDR1, CDR2 and MDR1. All studied <em>C. albicans</em> strains formed biofilms <em>in vitro</em>. Fluconazole-resistant strains had higher metabolic activity and biofilm mass (p = 0.011 and р = 0.012, respectively).</p> <h3 id="conclusions">Conclusions.</h3> <p>Resistance of RVVC pathogens in the North-West region of Russia is associated with increased biofilm formation, amino acid substitution Y132H and increased expression of the ERG11 and FLU1 genes.</p> http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p54/ Sat, 10 May 2025 13:39:58 +0000 http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p54/ <h3 id="objective">Objective.</h3> <p>To develop a quantitative model to assess the economic loss of irrational antimicrobial use and inaccurate antimicrobial resistance diagnosis.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The model&rsquo;s parameters were derived from a questionnaire survey designed to elucidate the characteristics of antimicrobial therapy practices and the impact of microbiological findings, including the frequency and consequences of diagnostic errors. The model&rsquo;s fundamental structure rests upon the relationship between the accuracy of microbiological diagnoses, the likelihood of irrational antimicrobial therapy, and the consequent economic losses. To improve the model&rsquo;s precision and generalizability, parameters encompassing gross regional product, population demographics, the prevalence of key community-acquired and nosocomial pathogens and their respective phenotypes, and antimicrobial drug prices were integrated.</p> <h3 id="results">Results.</h3> <p>Bacterial infections are prevalent in the practice of over 75% of surveyed specialists. Requests for clinical pharmacology consultation regarding infectious disease management are most frequently driven by multidrug-resistant pathogens and treatment failure. Electronic microbiology reports are accessed by 50,85% of specialists, with 65,62% utilizing in-house laboratory services. However, 36% lack readily available laboratory consultation. An association between interpretation of AST reports and choice of antimicrobial therapy was noted by 82,32% of specialists. In outpatient settings, mild and moderate adverse consequences of inappropriate antimicrobial therapy (IAT), affecting up to 25% of cases, were reported by 25,6% and 79,85% of specialists, respectively. In inpatient settings, moderate and severe adverse consequences of IAT (affecting &gt;25% of cases) were reported by 34,83% and 19,52% of specialists. Based on the developed model, with the specified parameters, a cohort of 1000 patients and a 10% error rate yields direct inpatient costs exceeding 1,7 million rubles, while total loss reaches 18,94 million rubles.</p> <h3 id="conclusions">Conclusions.</h3> <p>The developed model facilitates the estimation of economic consequences associated with irrational antimicrobial therapy, encompassing both direct and indirect costs, and exhibits considerable adaptability across diverse contexts. The findings underscore the need for further investigation to optimize interprofessional collaboration and the development of evidence-based strategies for mitigating the economic burden of antimicrobial resistance.</p> http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p33/ Sat, 10 May 2025 13:25:54 +0000 http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p33/ <h3 id="objective">Objective.</h3> <p>To study pharmacodynamics of meropenem alone and in combination with avibactam in an <em>in vitro</em> dynamic model; to evaluate effectiveness of meropenem against <em>K. pneumoniae</em> strains producing and not producing carbapenemases; to study impact of bacterial inoculum on meropenem activity and its effects.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p><em>K. pneumoniae</em> producing KPC and OXA-48 carbapenemases and non-producing strains were exposed to meropenem or its combination with avibactam (carbapenemase-producing strains only) in a modified <em>in vitro</em> hollow-fiber infection model (pneumoniae) simulating human pharmacokinetics of drugs administrated thrice daily for 5 days. The antimicrobial effect against the total population of <em>K. pneumoniae</em> was evaluated at different starting bacterial inocula (106 and 108 CFU/ml) by plating the samples on the agar media.</p> <h3 id="results">Results.</h3> <p>In the hollow-fiber infection model, the effect of meropenem was bactericidal for carbapenemase non-producing <em>K. pneumoniae</em> with MICs 2–4 mg/L, while carbapenemase-producing strains with comparable MICs of meropenem predominantly demonstrated rapid regrowth at both high and low starting inocula. The addition of avibactam led to an increased effect of meropenem and a decrease in the number of bacterial cells of all three carbapenemase-producing <em>K. pneumoniae</em> at both starting inocula.</p> <h3 id="conclusions">Conclusions.</h3> <p>Based on meropenem susceptibility data of <em>K. pneumoniae</em> without checking the ability to carbapenemase production it is impossible to guarantee a successful outcome of carbapenem therapy with both low (imitation of mild infection) and high (imitation of severe infection) inocula. Addition of avibactam significantly enhanced the effect of meropenem on all carbapenemase-producing strains.</p> http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p11/ Sat, 10 May 2025 13:18:02 +0000 http://cmac-journal.ru/en/publication/2025/1/cmac-2025-t27-n1-p11/ <h3 id="objective">Objective.</h3> <p>To determine role of ferritin (FT), procalcitonin (PCT) and their ratio (FT/PCT) in the differential diagnosis of viral lung injury and bacterial community-acquired pneumonia (CAP).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A prospective multicenter study included adult patients with CAP hospitalized in multidisciplinary hospitals from July to November 2023. All patients had their PCT and FT levels determined in addition to the standard examination protocol. Etiological diagnostics included microbiological examination of a respiratory sample and blood (in severe cases), rapid tests for pneumococcal and legionella antigenuria, and molecular testing of respiratory samples to detect DNA/RNA of the most common respiratory viruses and difficult-to-culture or non-cultivate bacterial pathogens.</p> <h3 id="results">Results.</h3> <p>Of the 152 patients included, the etiology of CAP was established in 96 cases: viral in 28 (29%), bacterial in 52 (54%), bacterial-viral coinfections in 16 (17%). Among bacterial pathogens, Mycoplasmoides pneumoniae accounted for a significant share – 62%. Comparative analysis of patients with CAP of viral and bacterial etiology revealed a lower level of FT in viral (127.5 versus 242 μg/L, p = 0.013), no significant differences were obtained in assessing PCT and the FT/PC ratio. After excluding cases of <em>M. pneumoniae</em> infection, significant differences remained: FT – 127.5 vs. 338.5 μg/L (p = 0.002), as well as PCT 0.1 vs. 0.4 ng/mL (p = 0.01). The cutoff values of FT &gt;146 μg/L (AUC = 0.76; OR = 8.0) and PCT &gt;0.15 ng/mL (AUC = 0.70; OR = 5.4) had a prognostic value for the diagnosis of bacterial CAP, when excluding cases of <em>M. pneumoniae</em> infection. Doubling the level of FT and PCT was associated with an increase in the likelihood of bacterial CAP by 1.8 (95% CI: 1.3-2.9) and 1.23 (95% CI: 1.05-1.48) times, respectively.</p> <h3 id="conclusions">Conclusions.</h3> <p>The study of the FT/PCT ratio did not have sufficient diagnostic accuracy in differentiating viral lung damage from bacterial CAP in adult patients in our study population; statistically significant but not clinically significant values were obtained when assessing PCT, and the determination of FT demonstrated some value; however, larger studies with groups of patients comparable in severity are needed for reliable use of this biomarker in clinical practice.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p522/ Fri, 28 Feb 2025 14:28:37 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p522/ <h3 id="objective">Objective.</h3> <p>To assess the ability of clinical isolates of opportunistic microorganisms to accumulate biofilm biomass under the influence of composite disinfectants.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 53 strains (49 – <em>K. pneumoniae</em>, 4 – <em>P. aeruginosa</em>) obtained from two multidisciplinary children’s hospitals at the city and regional levels. Specimens were collected from different loci of patients, medical devices, and environmental objects. To assess the reaction of biofilms (BF) of clinical isolates to the effects of disinfectants (DIs), three composite DIs were used: No. 1 – oxygen-containing, No. 2 – containing quaternary ammonium compounds and aldehydes, No. 3 – chlorine-containing.</p> <h3 id="results">Results.</h3> <p>All the studied strains were characterized by their ability to accumulate BF biomass of various degree: low – 15 (28.4%), moderate – 24 (45.2%), and high – 14 (26.4%). When exposed to DIs at the initial stage of adhesion, biomass of BF decreased in more than 70% of isolates, with chlorine-containing DI showing the greatest efficiency (No. 3). 24-hour BFs were resistant to the effects of DI No. 1 and DI No. 3; accumulation of BF biomass decreased only when using DI No. 2, which contained a complex of quaternary ammonium compounds and aldehydes. Isolates that initially had an increased ability to accumulate BF biomass were more resistant to the DIs effects at all stages of biofilm formation.</p> <h3 id="conclusions">Conclusions.</h3> <p>There is a need for further in-depth evaluation of the biocides effects on biofilm bacteria to prevent healthcare-associated infections.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p514/ Fri, 28 Feb 2025 14:26:32 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p514/ <h3 id="objective">Objective.</h3> <p>To perform comparative analysis of Bordetella protein profiling data and their dependence on various nutrient media.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>This prospective open single-center study, the protein profiles of B. pertussis, B. parapertussis, and B. bronchiseptica were studied; they had been grown on nutrient media with prescription combinations. We used casein-coal agar, Borde-Gengou Agar, Regan-Lowe Charcoal Agar as the basis of the nutrient medium. Defibrinated horse, sheep, human donor blood and human donor RBCs were used as a blood component. Penicillin, benzathine benzylpenicillin, cephalexin and antibiotic-free formulation were used as antimicrobial component. A total of 48 prescription combinations were tested. Identification of proteomic profiles of Bordetella spp. was carried out on MALDI-TOF mass spectrometer using Standard mode according to “Score” indicator.</p> <h3 id="results">Results.</h3> <p>The quantitative values of the “Score” indicator were subjected to comparative analysis depending on the used base, blood, antimicrobial, and combinations of individual components. According to “Score” indicator, the most reliable identification of Bordetella spp. was achieved using Borde-Gengou Agar basis (p = 0.035, Kruskal – Wallis test). No statistically significant differences were found when using other components.</p> <h3 id="conclusions">Conclusions.</h3> <p>The use of Borde-Gengou Agar base is the most appropriate for mass spectrometric identification of Bordetella spp.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p505/ Fri, 28 Feb 2025 14:24:18 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p505/ <h3 id="objective">Objective.</h3> <p>To study antimicrobial effect of extracellular metabolites of probiotic L. plantarum 8P-A3 strain on antibiotic-resistant <em>Klebsiella pneumoniae</em> and <em>Acinetobacter baumannii</em> isolated from infected wounds.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Bacteriological methods: semiquantitative sector method for extracting opportunistic microorganisms from an infected wound; a method for the identification of the antimicrobial activity of metabolites in a liquid milieu; The identification of bacteria was implemented with the help of the MALDI-TOF Autoflex mass spectrometer (Bruker Daltonics, Germany). Antimicrobial susceptibility testing was performed using SensiLaTest test systems (Erba Lachema, Czech Republic), analyzer Vitek 2 and disk-diffusion method. The prevalence of resistance genes was determined using BakResista GLA reagent kits by real-time PCR. In order to obtain L. plantarum 8P-A3 supernatant, cells were precipitated by centrifugation and then filtered using a membrane (Merck Millipore, Germany). Metabolomic profiling of the supernatant was implemented by HPLC/MS on mass spectrometer LCMS-8050 (Shimadzu, Japan). Whole-genome sequencing was performed on MiSeq platform (Illumina Inc., USA), and data processing was conducted using Trimmomatic, Spades, Prokka, RAST and Bagel 4 software tools.</p> <h3 id="results">Results.</h3> <p>All strains of <em>A. baumannii</em> and <em>K. pneumoniae</em> are multidrug-resistant and contain a range of beta-lactamases and carbapenemase in their genome. The results of metabolomic profiling showed that L. plantarum 8P-A3 supernatant contains a significant amount of lactic, valeric, isovaleric, succinic and acetic acids. Analysis of L. plantarum 8P-A3 genome found key enzymes for synthesis of lactic and acetic acids, hydrogen peroxide, lysozyme and plantaricins A, EF and NC8. This experiment proved that the supernatant completely inhibits the growth of nosocomial isolates of <em>A. baumannii</em> and <em>K. pneumoniae</em>.</p> <h3 id="conclusions">Conclusions.</h3> <p>Using whole-genome sequencing, the ability of L. plantarum 8P-A3 strain to synthesize extracellular metabolites with antimicrobial activity was determined. Metabolomic profiling of its supernatant proved the presence of high concentrations of organic acids in it. The presence of all these metabolites determined significant antimicrobial effect of the supernatant on multidrug-resistant nosocomial <em>K. pneumoniae</em> and <em>A. baumannii</em> isolates and showed potential for use as an adjunctive treatment of infected wounds.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p496/ Fri, 28 Feb 2025 14:22:01 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p496/ <h3 id="objective">Objective.</h3> <p>To analyze and compare multidrug-resistant <em>Klebsiella pneumoniae</em> (KP) strains isolated from different sites of the same patients.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 30 KP strains isolated from 15 patients treated in intensive care and surgical units in 2020–2021 were studied. Two strains isolated from one child were selected for analyses. One strain was isolated from a clinically significant site (blood/urine/wound/endotracheal aspirate or sputum), the other from a monitoring site (stool). Antibiotic susceptibility was determined using the broth microdilution method. The presence of beta-lactamase genes of the IMP, NDM, VIM, KPC, OXA-48, CTX-M groups and the mcr-1 gene were detected by real-time PCR. The virulence genes and K1/K2 capsular serotypes were determined by multiplex PCR with detection in 2% agarose gel. Biofilms were grown using flat-bottomed polystyrene plates followed by fixation, staining, elution and result detection. Sequence types (ST) were determined by multilocus sequence typing (MLST).</p> <h3 id="results">Results.</h3> <p>Most of KP strains were recognized as extensively drug-resistant pathogens (83.3%), five (16.7%) isolates were classified as multidrug-resistant pathogens. Carbapenemase production was detected in 86.7% strains. Carbapenem resistance was associated with OXA-48 carbapenemases (69.2%). Metallobeta-lactamases (MBL) of the NDM group were found in six (23.1%) strains. In two isolates, a combination of NDM and OXA-48 carbapenemases was discovered. Extended spectrum beta-lactamases (ESBLs) of the CTX-M group were detected in 93.3% isolates. All strains had the mrkD and entB virulence genes. The ybtS gene was found in 66.7% isolates. Eight (26.7%) strains harbored the iutA gene. The rmpA gene was detected in two isolates. Four isolates belonged to K2 serotype. The ability to form biofilms was detected in 93.3% strains. Most of the isolates produced biofilms of moderate intensity (57.1%), low-intensity biofilms were detected in 35.7% of isolates, and two strains formed strong biofilms. STs were represented by ST395 (40%), ST307 (20%), ST37 (20%), ST198 (6.7%), ST866 (6.7%), ST147 (6.7%).</p> <h3 id="conclusions">Conclusions.</h3> <p>The strains isolated from one patient had the same resistance and virulence determinants, belonged to the same sequence types and formed biofilms of the same intensity. The findings suggest that infections in the clinically significant site and the monitoring site were caused by the same KP strain.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p487/ Fri, 28 Feb 2025 14:20:12 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p487/ <h3 id="objective">Objective.</h3> <p>To evaluate the ability of bovhyaluronidaze azoximer to destroy biofilms formed by clinical strains of microorganisms.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 50 clinical strains of <em>Staphylococcus aureus</em> (n = 25), Staphylococcus epidermidis (n = 6), <em>Enterococcus faecalis</em> (n = 8), <em>Escherichia coli</em> (n = 9), <em>Candida albicans</em> (n = 2). Antimicrobial susceptibility testing was performed using broth microdilution method. Biofilm formation culturing in presence of antibiotics, or bovhyaluronidaze azoximer, or their combinations was assessed in Mueller-Hinton broth and brain heart broth in 96-well plates. Biofilms were fixed with 2,5% glutaraldehyde solution, stained with 0,25% crystal violet solution, which is extracted by 33% acetic acid solution.</p> <h3 id="results">Results.</h3> <p>Bovhyaluronidaze azoximer can destroy the matrix of preformed biofilms of methicillin-resistant strains of <em>S. aureus</em> as well as <em>S. epidermidis</em>, <em>E. coli</em>, <em>C. albicans</em> in concentrations of 64–1000 IU/ml, while exerting a dose-depend effective.</p> <h3 id="conclusions">Conclusions.</h3> <p>Bovhyaluronidaze azoximer combining with antibiotics will potentiate its antimicrobial effects by destroying the microbial biofilm matrix formed by microorganisms with multidrug resistance and facilitating the penetration of antibiotics to cellular targets.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p480/ Fri, 28 Feb 2025 14:17:49 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p480/ <h3 id="objective">Objective.</h3> <p>To study the population and genetic structure of <em>S. pneumoniae</em> isolated from children with cystic fibrosis (CF) and congenital malformations of the bronchi and lungs (CM) over the period 2011 to 2021, their serotype diversity in pre-vaccination and post-vaccination periods and susceptibility to antimicrobials.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 140 <em>S. pneumoniae</em> isolates (during 2011-2021) from respiratory samples of patients with CM or CF were included in the study. For all isolates serotypes, antimicrobial susceptibility, resistance genes to β-lactams and macrolides, and sequence types were determined.</p> <h3 id="results">Results.</h3> <p>We observed a general increase in non-vaccine serotypes mainly due to serotype 11A. Antimicrobial resistance was higher in vaccine serotypes compared to non-vaccine serotypes. There was an increase in the number of <em>S. pneumoniae</em> isolates with reduced susceptibility to penicillin among vaccine serotypes. All ermB/mef-containing islated belonged to the cMLSB phenotype and demonstrated high levels of macrolide resistance and multidrug resistance (MDR).</p> <h3 id="conclusions">Conclusions.</h3> <p>Continuous monitoring of the population structure of <em>S. pneumoniae</em> in children with chronic bronchopulmonary diseases is necessary. The detection of MDR serotypes with new sequence types indicates the great importance of continuing surveillance of antimicrobial resistance of <em>S. pneumoniae</em>.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p470/ Fri, 28 Feb 2025 14:14:23 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p470/ <h3 id="objective">Objective.</h3> <p>To develop a technology for producing Russia-made Mueller-Hinton broth and to compare its quality in terms of physicochemical and microbiological parameters with a foreign analog in trials using reference microbial strains sharing common and complex nutritional requirements.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The work investigated casein acid hydrolysates and Mueller-Hinton broths (MHBs) produced by the Federal Budgetary Institution of Science SRCAMB (MHB–Obolensk) and by BD BBL (MHB–BD) through testing 7 test strains of <em>E. coli</em> ATCC 25922, <em>S. aureus</em> ATCC 29213, <em>P. aeruginosa</em> ATCC 27853, <em>E. faecalis</em> ATCC 29212, <em>S. pneumoniae</em> ATCC 49619, <em>H. influenzae</em> ATCC 49766, and C. jejuni ATCC 33560 against 21 antibiotics (Sigma) by the broth microdilution method procedure according to EUCAST methodology. The latter three strains were cultured in broth supplemented with 5% lysed horse blood (Ecolab) and 20 mg/l of β-NAD (Sigma). Totally 192 tests for each broth were carried out. Physicochemical and microbiological quality parameters were determined according to GOST R 70393-2022. The content of divalent metal ions was determined by inductively coupled plasma atomic emission spectrometrу.</p> <h3 id="results">Results.</h3> <p>A technology allowing the production of Russia-made MHB of the conventional composition based on hydrochloric acid casein hydrolysate with a standardized content of calcium, magnesium ions and a reduced content of manganese, zinc and thymidine ions has been developed. Physicochemical (pH, amine nitrogen, chlorides) and microbiological (sensitivity, microbial growth rate, stability of their basic biological properties, and antimicrobial susceptibility) quality parameters did not differ from those for MHB–BD. MIC values for MHB–Obolensk and MHB–BD were consistent with targets in 162 tests (84.4%) and 168 tests (87.5%), respectively, and differed from the target by +/-one dilution in 30 (15.6%) and 21 (11%) tests, respectively. In analyzing the combination of meropenem – <em>P. aeruginosa</em> in MHB–BD, MICs exceeded the admissible interval by one double dilution in three tests. The content of calcium, magnesium, manganese and zinc ions in the broths complies with international standards. However, the concentration of the latter in MHB-BD turned out to be three times higher and amounted to 1.1 mg/l being a possible cause of the error in determining the MIC of meropenem. The results obtained require further study involving microbial clinical strains in order to optimize admissible concentrations of zinc ions.</p> <h3 id="conclusions">Conclusions.</h3> <p>Conventional a Russia-made MHB that meets the requirements of international standards has been developed. The broth is not inferior to its foreign analog in quality as shown in comparative studies using reference strains with common and complex nutritional needs.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p462/ Fri, 28 Feb 2025 14:12:09 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p462/ <h3 id="objective">Objective.</h3> <p>Conduct a comparative assessment of the frequency and spectrum of antimicrobial resistance of <em>Mycobacterium avium</em> isolated from patients of a phthisiopulmonology clinic in the pre-Covid period (2018–2019) and during the COVID-19 pandemic (2020–2023).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The antimicrobial sensitivity of <em>M. avium</em> isolates was determined to 8 antimicrobial drugs: amikacin, clarithromycin, linezolid, moxifloxacin, ciprofloxacin, doxycycline, rifabutin, rifampicin. Drug susceptibility testing was performed using serial broth microdilution method according to published CLSI guidelines, M24S, 2023. Interpretation of the results, classifying <em>M. avium</em> into one of three categories: sensitive, intermediate, resistant, was carried out based on a comparison of the values of the minimum inhibitory concentrations (MIC) of antimicrobial drugs with the breakpoint values of these parameters published in the CLSI M24S, 2023. <em>M. avium</em> complex breakpoints were used for amikacin, clarithromycin, linezolid, and moxifloxacin. For ciprofloxacin, doxycycline, rifabutin, rifampicin, breakpoints for other slow-growing non-tuberculous mycobacteria (NTM) (M. kansasii and M. marinum) were used according to the rules in section CLSI M24S, 2023 “Non-species related breakpoints”.</p> <h3 id="results">Results.</h3> <p>A comparative analysis of antimicrobial resistance of <em>M. avium</em> in the pre-Covid period (2018– 2019) and during the COVID-19 pandemic (2020–2023) showed an increase in the proportion of <em>M. avium</em> isolates resistant to clarithromycin (from 1.1% to 20.1%, p &lt; 0.0001), moxifloxacin (from 11.0% to 29.2%, p = 0.0007) and an increase in the proportion of isolates with intermediate drug sensitivity to clarithromycin (from 5.6% to 17.6%, p = 0.0080) during the COVID-19 pandemic. The opposite trend is noteworthy – an increase in the proportion of <em>M. avium</em> isolates sensitive to amikacin during the COVID-19 pandemic (from 55.5% to 79.6%, p &lt; 0.0001) and a decrease in the proportion of isolates resistant to amikacin (from 36% to 4.4%, p &lt; 0.0001). In addition, there was a decrease in the proportion of isolates with intermediate drug sensitivity to ciprofloxacin (from 18.8% to 9.7%, p = 0.0288) and to linezolid (from 27.7% to 17.2%, p = 0.039).</p> <h3 id="conclusions">Conclusions.</h3> <p>The data obtained in this work on the increase in the frequency of occurrence of <em>M. avium</em> isolates resistant to main and reserve antimicrobials during the COVID-19 pandemic requires the search for new antimicrobials that are effective against infection caused by <em>M. avium</em>. It is necessary to expand data on the MIC breakpoint values of new and existing antimicrobials for <em>M. avium</em> and to develop a reasonable criterion for establishing clinical categories of sensitivity and resistance, as well as to revise recommendations and expand the group of antimicrobials tested for drug susceptibility of NTM to determine treatment regimens.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p439/ Fri, 28 Feb 2025 14:07:08 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p439/ <h3 id="objective">Objective.</h3> <p>To develop criteria for the interpretation and quality assurance of the results of susceptibility testing of <em>Enterobacterales</em> and <em>P. aeruginosa</em> to cefepime-sulbactam.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 1035 clinical <em>Enterobacterales</em> isolates and 407 <em>P. aeruginosa</em> isolated in 2023 from hospitalized patients with nosocomial and community-acquired infections. Determination of cefepime and cefepime-sulbactam MICs was performed by broth microdilution method in Mueller-Hinton II broth in accordance with ISO 20776 1:2019. Determination of MICs was performed in the concentration ranges of cefepime: 0.06–64 mg/L for <em>Enterobacterales</em>, 0.125–128 mg/L for <em>P. aeruginosa</em>, without sulbactam, as well as in the presence of a fixed sulbactam concentration (4 mg/L). Testing was performed in 25 sets simultaneously with testing of control strains – <em>E. coli</em> ATCC 25922, K. quasipneumoniae ATCC 700603 and <em>P. aeruginosa</em> ATCC 27853 (in 5 independent repeats for each strain in each set). Susceptibility to cefepime-sulbactam by disk-diffusion method was determined using Mueller-Hinton agar and disks containing a combination of cefepime and sulbactam (30 + 10 µg, Lot No. 111123002, Liofilchem S.r.l., Italy) according to the standard EUCAST method. Zones of growth inhibition (ZGI) values were determined in 3 replicates for all clinical isolates and 5 replicates for each control strain. Standard methods of descriptive statistics and Microsoft Excel charting tools were used to analyze the distributions of MIC and ZGI values. Calculation of the borderline values of ZGI for determining clinical susceptibility categories for cefepime-sulbactam was performed by constructing a negative linear regression reflecting the relationship between log2(MIC) and ZGI values, and determining the ZGI values corresponding to the borderline values of cefepime MIC established by EUCAST.</p> <h3 id="results">Results.</h3> <p>For the two most common <em>Enterobacterales</em> species (<em>E. coli</em> and <em>K. pneumoniae</em>) close values of regression coefficients and good negative correlation of MIC and ZGI values were established (R2 &gt; 0.8). Subanalysis of the data on the distribution of MIC and ZGI values for other <em>Enterobacterales</em> species showed a low correlation (R2 = 0.4947) between these parameters in species producing intrinsic AmpC cephalosporinases: C. freundii, E. cloacae complex spp., H. alvei, K. aerogenes, M. morganii, Providencia spp. and Serratia spp. (isolates belonging to these species were excluded from further analysis). The final sample for calculating cefepime-sulbactam ZGI breakpoints for <em>Enterobacterales</em> included 890 isolates (2670 comparisons) belonging to 9 species: C. koseri, <em>E. coli</em>, K. oxytoca, <em>K. pneumoniae</em>, <em>P. mirabilis</em>, P. penneri, P. vulgaris, R. ornithinolytica and S. enterica. The R2 value of the linear regression was 0.8912. The calculated breakpoints for ZGI: S ≥ 26 mm, R &lt; 22 mm. Values of 22–25 mm coinciding with the clinical susceptibility category “I” was also marked as “zone of technical uncertainty – ZTN” according to the EUCAST definition, because it includes a significant number of isolates that can be categorized differently when determining sensitivity by DDM and on the basis of MIC estimation. For <em>P. aeruginosa</em>, the R2 value of the linear regression was 0.8131; the calculated breakpoint for ZGI was R &lt; 25 mm; the zone of technical uncertainty was 24–27 mm. For control strains: ZGI values of K. quasipneumoniae ATCC 700603 differed withing 4 mm (range: 25–28; mean: 27.6; median: 28 mg/L); <em>E. coli</em> ATCC 25922 – withing 2 mm (range: 33–35; mean: 34.7; median: 35 mg/l); <em>P. aeruginosa</em> ATCC 27853 – withing 2 mm (range: 31–33; mean: 31.9; median: 32 mg/l).</p> <h3 id="conclusions">Conclusions.</h3> <p>The developed criteria for interpretation and quality assurance of the results of susceptibility testing of <em>Enterobacterales</em> and <em>P. aeruginosa</em> to cefepime-sulbactam can be recommended for approval and inclusion in the Russian recommendations “Determination of sensitivity of microorganisms to antimicrobial agents”.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p417/ Fri, 28 Feb 2025 14:02:10 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p417/ <h3 id="objective">Objective.</h3> <p>To evaluate the results of implementing the AMRcf and AMRcloud platforms for microbiological surveillance studies of patients with cystic fibrosis (CF) into the routine practice of a microbiological laboratory.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study was performed on the basis of the Department of Microbiology of the Clinical diagnostic laboratory of the Clinics of the Samara State Medical University. To perform the study, the following computer programs were introduced into routine practice: AMRcf (online microbiological registry for CF patients) and AMRcloud (online platform for analysis of collected data on antibiotic resistance). The results of microbiologic studies conducted from 2018 to 2023 from 16 regions of the Russian Federation were retrospectively entered into the AMRcf online platform.</p> <h3 id="results">Results.</h3> <p>A total of 3052 isolates isolated from CF patients were entered into the AMRcf registry database for individual analysis. The generated data pool in AMRcf was tested for automated upload to the AMRcloud platform, which was subsequently used to analyze the accumulated data at the level of the study population. Implementation of the AMRcf platform allowed to provide: storage and access to microbiological data of CF patients; integration of data from different regions and sources, individual microbiological anamnesis for each patient in real time, interaction of specialists from different fields dealing with the problem of microbiological diagnosis and antimicrobial therapy in CF patients.</p> <h3 id="conclusions">Conclusions.</h3> <p>Implementation of the AMRcf online registry and the AMRcloud online platform in the workflow of the microbiology laboratory enables individualized surveillance of the microbiota of cystic fibrosis patients in different regions of the Russian Federation. Data from the AMRcf and AMRcloud online platforms can be used in routine practice by microbiologists, clinicians, and epidemiologists.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p411/ Fri, 28 Feb 2025 13:59:37 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p411/ <h3 id="objective">Objective.</h3> <p>To compare the species diversity of non-tuberculous mycobacteria (NTM) isolated from patients of phthisiopulmonary institutions in 2018–2019 (“pre-Covid” period) and in 2020–2023 (during the COVID-19 pandemic).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We identified 937 clinical isolates of NTM, isolated from patients undergoing differential diagnosis of tuberculosis and other respiratory diseases at The National Medical Research Center o Phthisiopulmonology and Infectious Diseases under the Ministry of Health of the Russian Federation (NMRC PhPI) and in other phthisiopulmonological institutions of the Russian Federation in 2018–2019 (“pre-Covid” period, n = 217) and in 2020–2023 (during the COVID-19 pandemic, n = 720).</p> <h3 id="results">Results.</h3> <p>It was found that during the COVID-19 pandemic, fast-growing (12.64% versus 6.91%, p = 0.0268) were more common than before the pandemic; slow-growing non-tuberculous mycobacteria became less common during the pandemic (87.36% versus 93.09%, p = 0.0268). Among the slowgrowing species the predominant species were <em>M. avium</em>, M. chimaera/intracellulare (<em>Mycobacterium avium</em> complex) and M. kansasii (Mycobacterium kansasii complex). During the COVID-19 pandemic significantly more species of non-tuberculous mycobacteria were discovered: 16 species of slowgrowing (M. celatum, M. colombiense, M. marselience, M. timonense, M. engbaekii, M. heraklionense, M. nonchromogenicum, M. europaeum, M. mantenii, M. nebraskense, M. branderi, M. conspicuum, M. saskatchewanense, M. scrofulaceum, M. heckeshornense, M. szulgai) and 15 fast-growing species (M. chelonae, M. immunogenum, M. salmoniphilum, M. porcinum, M. senegalense, M. septicum, M. mageritense, M. mucogenicum, M. neoaurum, M. murale/tokaiense, M. arabiense, M. asiaticum, M. chubuense, M. novocastrense, M. stephanolepidis).</p> <h3 id="conclusions">Conclusions.</h3> <p>In this study we showed differences in NTM species diversity in 2018–2019 (during the “pre-Covid” period) and in 2020–2023 (during the COVID-19 pandemic). Additional studies are needed to assess the impact of the COVID-19 pandemic on the incidence and species diversity of NTM, as well as their association with NTM diseases diagnosed in the corresponding patients with NTM.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p401/ Fri, 28 Feb 2025 13:49:57 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p401/ <h3 id="objective">Objective.</h3> <p>To analyze the profile of bacterial pathogens in patients with extremities wounds resulting from mine-blast injuries, and their susceptibility to antibacterial drugs.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The prospective observational study enrolled 234 patients who suffered injuries to the lower and/or upper extremities in the period from 4 to 36 days (mean 14.9 ± 7.4 days) before admission to the hospital. All study participants were men. The age of study patients ranged from 19 to 59 years (mean 35.8 ± 8.4 years). During the hospital stay, microbiological analysis of wound samples obtained during surgical treatment of wounds was regularly performed. The wound samples were cultured on nutrient media and microorganisms were identified in accordance with standard methods and procedures.</p> <h3 id="results">Results.</h3> <p>According to the results of microbiological analysis of wound samples, the growth of microorganisms was detected in 91.5% of patients. <em>Acinetobacter baumannii</em> (44.4%), <em>Enterococcus faecalis</em> (43.9%), <em>Pseudomonas aeruginosa</em> (26.2%) and <em>Klebsiella pneumoniae</em> (17.3%) were most often detected in the initial study. In 22.2% of patients, wounds were infected with one microorganism; in 77.8%, associations of two or more pathogens were found, most often <em>A. baumannii</em> and <em>E. faecalis</em> (36%) and <em>P. aeruginosa</em> and <em>E. faecalis</em> (18%). In total, pan-resistant, extremely resistant and multiresistant among <em>A. baumannii</em> were 40.5, 36.5 and 9.5%, among <em>K. pneumoniae</em> – 42.3, 46.1 and 7.7%, <em>P. aeruginosa</em> – 17.9, 33.3 and 33.3% of isolates. Almost all isolates of <em>E. faecalis</em> (98.9%) were sensitive to the tested antibacterial drugs. The majority (78.2%) of patients were prescribed antibiotics; the most used antibiotics were amikacin (42.1%), vancomycin (33.3%), and cefepime (28.4%). Combined antibacterial therapy was used in 57.2% of cases. The most frequently prescribed combinations of antibiotics were cefepime with sulbactam, vancomycin with amikacin, and meropenem with vancomycin. Along with antibacterial drugs, all patients underwent surgical treatment of wounds and vacuum-assisted therapy. In 67 patients (41.1%) the same microbiota remained in the wounds during hospital treatment. In 96 (58.9%) patients, other pathogens were identified in a series of subsequent microbiological analyses. The most common new pathogens were <em>E. faecalis</em> (28.4%), <em>A. baumannii</em> (24.2%), and <em>K. pneumoniae</em> (18.9%).</p> <h3 id="conclusions">Conclusions.</h3> <p>The study results indicate a high incidence of wound infection in patients with combat injuries to the extremities. The most frequently identified bacterial pathogens were <em>A. baumannii</em>, <em>E. faecalis</em> and <em>P. aeruginosa</em>. Among enterobacteria and <em>A. baumannii</em>, pan-resistant and extremely resistant prevailed; most enterococci demonstrated susceptibility to traditionally used antibacterial drugs.</p> http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p396/ Fri, 28 Feb 2025 13:45:35 +0000 http://cmac-journal.ru/en/publication/2024/4/cmac-2024-t26-n4-p396/ <h3 id="objective">Objective.</h3> <p>Seroyping of the <em>Streptococcus pneumoniae</em> strains obtained from patients with invasive and non-invasive forms of pneumococcal infection circulating in Russia using whole-genome sequencing.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The 144 invasive and 90 non-invasive <em>S. pneumoniae</em> strains isolated in 2002– 2023 during the multicenter epidemiological study «PEGASus» were investigated. Real-time PCR and whole-genome sequencing were used to determine serotypes. The 16 serotyping targets were examined by PCR technique. Whole-genome sequencing was performed on the Illumina equipment. Sequencing results were processed using the PubMLST software and PneumoCaT, SeroBA and PneumoKITy programs.</p> <h3 id="results">Results.</h3> <p>The whole-genome sequences were obtained and strains serotypes were determined, while the efficiency of serotype determination by software was 97% (serotypes of 8 strains were determined ambiguously). The serotypes distribution in the invasive and non-invasive strains differed, along with it the proportion of invasive strains included as vaccine components was higher than non-invasive ones. Statistically significant differences between the groups of invasive and non-invasive strains were observed for 13-, 15- and 23-valent vaccine components.</p> <h3 id="conclusions">Conclusions.</h3> <p>The whole-genome based analysis allows us to obtain comprehensive information about the genetic and antigenic features of <em>S. pneumoniae</em> pathogens. The information about serotypes distribution allows the vaccines effectiveness and provides the necessary information for routine PCR based serotypes monitoring and planning vaccination.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p384/ Thu, 14 Nov 2024 11:10:34 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p384/ <h3 id="objective">Objective.</h3> <p>To compare analytical parameters and sensitivity between BACT/ALERT® 3D 60 and Yunon® Labstar 50.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 20 species of clinically significant microorganisms isolated from blood (20 strains for each facultative anaerobic species and 10 strains for each aerobic species). For each strain, individual volumes of the inoculation dose were selected with the control of CFU value. In the case of obtaining a stable CFU value in the range 2–10 per 100 µl of bacterial cell suspension, 100 µl of suspension was inoculated into vials with nutrient media for each analyzer, followed by an analysis of the cultivation time, the presence or absence of a growth signal, and average CFU values. Aliquots of the vials contents were also inoculated onto solid nutrient media to evaluate false positive and false negative results.</p> <h3 id="results">Results.</h3> <p>It was revealed that the main analytical parameters of both devices were comparable. In addition, for two blood culture systems, the maximum limit value of CFU per sample was set, at which the probability of the growth signal absence from both analyzers significantly increased – 2 CFU per vial. At this value and values below, the analyzers did not detect the growth of microorganisms significantly more often. Also, a comparable median inoculation dose of 5 CFU per vial was established for both devices.</p> <h3 id="conclusions">Conclusions.</h3> <p>The devices included in the study have comparable analytical parameters and allow to obtain a positive growth signal after inoculating material containing &lt; 10 CFU per vial. However, it is necessary to consider increased probability of a negative result in case of inoculation dose equal to CFU ≤ 2.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p378/ Thu, 14 Nov 2024 11:08:23 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p378/ <h3 id="objective">Objective.</h3> <p>To identify point mutations in 23S rRNA gene associated with phenotypic drug resistance to clarithromycin (CLR) in clinical isolates of <em>H. pylori</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 50 <em>H. pylori</em> clinical isolates (2014–2022) from adult patients with chronic gastritis (n = 32), duodenal ulcer (n = 11) and gastric cancer (n = 1) were included in this study. Of 50 isolates, 30 were obtained from newly diagnosed patients, 20 – from previously treated patients after eradication failure. All isolates were cultured on supplemented Columbia agar and incubated under microaerophilic conditions (GasPak 100). Antibiotic susceptibility testing was performed by disc diffusion method. The PCR products (1402 bp) of the 23S rRNA gene were sequenced by Sanger approach. The DNA sequences were compared to the <em>H. pylori</em> 26695 reference using Unipro UGENE v.38.1.</p> <h3 id="results">Results.</h3> <p>A total of 30 <em>H. pylori</em> isolates were determined as CLR-resistant and 20 isolates as CLR-susceptible. The A2147G point mutation was detected in 17 (56,7%) CLR-resistant isolates and one (5.0%) CLR-sensitive isolate (p = 0,0002). The other point mutation A2146G was found exclusively in 13.3% (⁴&frasl;₃₀) of CLR-resistant isolates (p = 0,14). None of the CLR-resistant isolates carried two A2146G/A2147G mutations simultaneously, whereas 9 (30.0%) had neither of them. The agreement between genotypic and phenotypic susceptibility to CLR based on both A2146G + A2147G mutations was 70.0%. All clinical isolates obtained from previously treated patients (n = 20) were assigned to CLR-resistant group. Of these, 16 (80.0%) carried either A2146G or A2147G mutations, while among newly diagnosed patients (n = 30) only 5 isolates (16.7%) had one of two mutations (p = 0,003). The other point mutations out of 2146–2147 positions identified were G1567T, C1568A/T, A1825G, G1830A, T1834C, T2186C, but with no association with phenotypic drug resistance (p &gt; 0.05).</p> <h3 id="conclusions">Conclusions.</h3> <p>Our study showed that among all variants of nucleotide substitutions in 23S rRNA gene, the only one (A2147G) is significantly associated with phenotypic resistance of <em>H. pylori</em> to CLR. Despite the low frequency of A2146G point mutation, combination of A2146G/A2147G mutations can be used as a predictor of phenotypic resistance of Russian <em>H. pylori</em> clinical isolates.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p370/ Thu, 14 Nov 2024 11:06:19 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p370/ <h3 id="objective">Objective.</h3> <p>To evaluate the involvement of P. jirovecii in the infectious and other diseases in children and adults with immunosuppression of various origin. To assess the risk of infection with P. jirovecii, pneumocystosis and its spread by healthcare workers.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>An analysis of the results of a study of 1,446 samples of peripheral blood sera from patients, both children and adults, who were treated in hospitals of various profiles in Moscow and represented an increased risk group for pneumocystosis. IgM and IgG class antibodies were determined by enzyme immunoassay (ELISA). Indirect immunofluorescence assay was used to detect all forms of pneumocysts (cyst, precyst, trophozoite) in sputum.</p> <h3 id="results">Results.</h3> <p>The incidence of pneumocystosis infection was significantly higher in children with druginduced immunodeficiency after a related liver transplant (70.1%) than among children with HIV-related immunodeficiency (36.7%), t = 2.4. Markers of acute pneumocystosis were found in 36.7% of children who underwent transplantation and 10.0% with HIV infection (t = 2.4). The examination of HIV-infected adults, as well as patients whose HIV infection is complicated by tuberculosis, tuberculosis patients without HIV infection and healthy adults of the comparison group (donors) showed that markers of acute pneumocystosis were most often detected in tuberculosis patients – in 27.1% of cases, in 22.8% of HIVinfected with tuberculosis and in 21.1% of patients with HIV infection, while in the comparison group, markers of acute pneumocystosis were found in only 2.7% of donors. Markers of pneumocystosis were found in 62.6% of children with obstructive bronchitis, of whom 30.4% of patients had an active infection. In children with long-term subfebrile temperature, these indicators were 56.4% and 36.9%. Observation of frequently ill children revealed markers of pneumocystosis in 21.0%, more than half of them were carriers of P. jirovecii (11.3%), and 6.4% were diagnosed with acute pneumocystosis, but only 3.2% of the children had asymptomatic infection. According to a study of healthcare workers in several Moscow hospitals, they should be considered as a double-risk group due to the possibility of both infection and spread of pneumocystosis. Markers of acute infection (IgM, IgM + IgG) were found in 20.0–28.6% of healthcare workers. Acute pneumocystosis was diagnosed 2.4–3.4 times more frequently among healthcare workers than in the comparison group (8.3%).</p> <h3 id="conclusions">Conclusions.</h3> <p>All of the studied pediatric and adult populations are at increased risk of contracting and spreading of pneumocystosis, which makes it necessary to monitor this infection in high-risk groups.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p356/ Thu, 14 Nov 2024 10:52:49 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p356/ <h3 id="objective">Objective.</h3> <p>To determine spectrum and prevalence of genetic determinants of macrolide and fluoroquinolone resistance in <em>Mycoplasma genitalium</em> from patient in dermatovenerology clinics of two Russian megalopolises: Moscow and St. Petersburg in 2021–2024.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 530 M. genitalium DNA-positive specimens (urethral and cervical swabs) obtained from men and women from the STD clinic in St. Petersburg and Сlinical facilities of the Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology of the Moscow Department of Health Care were analyzed. Screening in local laboratories was performed using commercially available kits for isolation and detection of M. genitalium DNA. Primary screening for resistance-associated mutations was carried out using the previously developed protocol of PCR-RT (allows detecting any nucleotide substitutions in the 23S rRNA gene and parC gene) [1]. The results were confirmed using Sanger sequencing [2]. The study results are presented as an open project on the AMRcloud platform (<a href="https://amrcloud.net/ru/project/demares/" target="_blank">https://amrcloud.net/ru/project/demares/</a>).</p> <h3 id="results">Results.</h3> <p>185 and 345 M. genitalium-positive samples from St. Petersburg and Moscow, respectively, showed the presence of a specific signal in both the 23S rRNA gene and parC gene in primary screening. The macrolide-resistance mutations was in 29% (⁵⁴&frasl;₁₈₅) of samples from St. Petersburg and in 28% (⁹⁷&frasl;₃₄₅) from Moscow, with a predominance of the A2059G 23S rRNA genotype of M. genitalium in 57% (³¹&frasl;₅₄) and 68% (⁶⁶&frasl;₉₇), respectively. The second largest proportion were samples in which the nucleotide substitution A→G at position 2058 was detected: ²³&frasl;₅₄ (42%) from St. Petersburg and ³⁰&frasl;₉₇ (30%) from Moscow. Mutations to fluoroquinolones were detected in the parC gene in ⁴⁷&frasl;₁₈₅ (25%) and ⁷³&frasl;₃₄₅ (21%) samples from St. Petersburg and Moscow, respectively. In Moscow, the amino acid substitution S80I prevails 39% (²⁹&frasl;₇₃), the second most abundant D84N occured in 35% (²⁶&frasl;₇₃), in St. Petersburg, the similar ratio of S80I was 44% (²¹&frasl;₄₇), D84N was 29% (¹⁴&frasl;₄₇). In Moscow, seven samples carried the third most common mutation S80N, which is 9%, in St. Petersburg this figure, was twice as high – 19% (⁹&frasl;₄₇). The share of other mutations in the two cities was not more than 1% (D84G, D84Y and S81P). In St. Petersburg, simultaneously with mutations in 23S rRNA, the presence of amino acid substitutions in the ParC QRDR was also confirmed, which represented a case of combined resistance to both groups antibiotics; this level was 1.5 times higher than in Moscow (40% (³⁹&frasl;₉₇)) and amounted to 61% (³³&frasl;₅₄). The most common combination of mutations was A2059G (23S rRNA) + S80I (parC), which made up to 33% (¹⁸&frasl;₅₄) in St. Petersburg and 25.7% (²⁵&frasl;₉₇) in Moscow. The second most abundant genotype – A2058G (23S rRNA) + D84N (parC) accounted for 14% (⁸&frasl;₅₄) and 10% (¹⁰&frasl;₉₇), respectively.</p> <h3 id="conclusions">Conclusions.</h3> <p>The high level of resistance to macrolides and fluoroquinolones in M. genitalium in two major Russian cities is a significant problem and need for comprehensive resistance testing before prescribing therapy and surveillance programs. The introduction of adapted diagnostic and therapeutic algorithms will reduce the duration of drug administration, increase the effectiveness of therapy and reduce the burden on the health care system. The use of long-term monitoring will improve the policy of antibiotic prescription and reduce the growth of antimicrobial resistance and its spread in Russia.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p345/ Thu, 14 Nov 2024 10:50:30 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p345/ <h3 id="objective">Objective.</h3> <p>To investigate the prevalence of carbapenemase-encoding genes carriage in patients at hospital admission.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The prospective single-center cross-sectional study was performed in Moscow Multidisciplinary Clinical Center «Kommunarka» from 15.09.2022 till 15.08.2023. Adult patients without signs of gastrointestinal, upper and lower respiratory tract infections were included to research at fist 24 hour after hospital admission. Rectal swab and oropharyngeal swab were collected from each patient. Additional lower respiratory tract samples were collected from patients who were undergoing mechanical ventilation. The collected samples were tested by polymerase chain reaction using AmpliSens reagent kits to identify crabapenemase-encoding genes: blaOXA-58, blaOXA-51, blaOXA-40, blaOXA-23, blaVIM, blaIMP, blaOXA-48, blaNDM and blaKPC.</p> <h3 id="results">Results.</h3> <p>A total of 737 patients aged 18 to 94 were included, 442 of them were females and 295 were males. Carriage of genes in at least one locus was found in 12.6% of patients. 70.9% of patients carried only one type of genes, but 16.1% carried two different types of genes and 12.9% carried from 3 to 6 different types of genes. Males were carriers more often, then females (18.3% and 8.6% respectively). The most common gene was blaOXA-48 (23.1%), followed by blaNDM (15.4%). Genes blaKPC and blaOXA-51 were detected with the same frequency (14.7%). The other genes were less common, from 0.6% (blaIMP) to 10.3% (blaOXA-51). Genes blaOXA-48, blaNDM and blaKPC were more common in rectal swabs, and blaOXA-58 and blaOXA-51 predominated in upper respiratory tract samples. In lower respiratory tract samples blaOXA-48, blaKPC and blaOXA-51 occurred with equal frequency. In ICU patients the prevalence of carriage was 35.1% compared to 8.5% among ward patients. The carriage rate was the highest among patients from therapeutic wards (17.5%) and the lowest in patients from hematology wards (3.0%).</p> <h3 id="conclusions">Conclusions.</h3> <p>Our study is one of the first in Russia to evaluate the prevalence of community-acquired carriage of carbapenemase genes. The features we discovered have potential clinical significance and allow us to draw some conclusions for our center, but multicenter studies of a similar design are needed to identify general patterns.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p338/ Thu, 14 Nov 2024 10:47:36 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p338/ <h3 id="objective">Objective.</h3> <p>To perform phylogenetic analysis to assess ongoing changes in population structure of Russian clinical isolates of <em>N. gonorrhoeae</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The object of the study was 34 clinical isolates of <em>N. gonorrhoeae</em> obtained from dermatovenerological medical institutions of the Russian Federation in the period 2022–2023. The cultures were spread on chocolate agar with 1% ISOVitalex growth additive and 1% VCAT selective additive (Becton Dickinson, USA). Mass spectrometric studies were performed using MALDI-TOF mass spectrometer (Bruker Daltonics, Germany). Susceptibility testing of <em>N. gonorrhoeae</em> to 6 antimicrobials (penicillin, spectinomycin, ceftriaxone, tetracycline, azithromycin, and ciprofloxacin) was performed by serial dilutions in agar with determination of minimum inhibitory concentrations. Genomic DNA was extracted from <em>N. gonorrhoeae</em> cultures using the Proba-NK kit (DNA-Technology, Russia). Molecular typing of the strains was performed on MiSeq platform (Illumina, USA).</p> <h3 id="results">Results.</h3> <p>Genotyping of 34 <em>N. gonorrhoeae</em> strains from 4 Russian regions was performed using NG-STAR protocol to identify genotypic determinants associated with antibiotic resistance. A total of 19 sequence types included in 7 previously described clonal complexes (CC) were identified. The most representative CC among the studied strains were 199 and 427 (38.2% and 26,5%, respectively). Resistance to 6 antimicrobials associated with variability of penA, mtrR, porB, ponA, gyrA, parC and 23S rRNA gene fragments was detected in 44.1% of strains.</p> <h3 id="conclusions">Conclusions.</h3> <p>A number of molecular types of <em>N. gonorrhoeae</em> associated with phenotypic multidrug resistance was identified, which confirms the importance of comprehensive laboratory studies of clinical isolates to prevent spread of antimicrobial resistance in Russia.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p328/ Thu, 14 Nov 2024 10:19:42 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p328/ <h3 id="objective">Objective.</h3> <p>To study <em>in vitro</em> activity of antimicrobials against clinical isolates obtained from patients with community-acquired urinary tract infections (UTIs) in various regions of Russia in 2023.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 1098 isolates obtained from the urine of children and adults of both sexes of all age groups with acute and exacerbation of recurrent community-acquired UTIs, including pregnant women with asymptomatic bacteriuria. Isolates were collected in 29 centers in 21 cities of Russia in 2023 as part of a multicenter prospective epidemiological study of the dynamics of antibiotic resistance of pathogens causing community-acquired UTIs in different subsets of patients (&laquo;DARMIS-2023&raquo;). The categories of susceptibility of isolates to antimicrobial drugs were based on the breakpoint values of minimum inhibitory concentrations (MIC) in accordance with the Russian recommendations &laquo;Determination of susceptibility of microorganisms to antimicrobial drugs&raquo; (Version 2024-02) and the updated EUCAST criteria (v. 14.0, 2024).</p> <h3 id="results">Results.</h3> <p><em>Enterobacterales</em> accounted for a total of 88.1% of all isolated bacterial pathogens (89.6% in the adult subpopulation; 82.8% in the pregnant subpopulation and 89.6% in the subpopulation of children and adolescents under 18 years of age). The most prevalent species were <em>Escherichia coli</em> (72.2% in the adult subpopulation; 72.8% in the pregnant women subpopulation and 68.9% in the children and adolescents under 18 years of age subpopulation) and <em>Klebsiella pneumoniae</em> (10.8% in the adult subpopulation; 4.8% in the pregnant women subpopulation and 9.8% in the children and adolescents under 18 years of age subpopulation). Of the oral drugs, the minimal resistance in <em>E. coli</em> was demonstrated for nitrofurantoin (0.4% of isolates in the adult subpopulation; 0.0% in the pregnant women subpopulation and 1.6% in the children and adolescents under 18 years of age subpopulation) and fosfomycin (9.6% of isolates in the adult subpopulation; 4.4% in the pregnant women subpopulation and 1.6% in the children and adolescents under 18 years of age subpopulation). Of the parenteral agents, meropenem and amikacin had the highest activity: 0.8% and 1.0% resistant <em>E. coli</em> in the adult subpopulation; no resistant <em>E. coli</em> in the pregnant subpopulation; 0.0% and 0.8% in the children and adolescents under 18 years of age subpopulation, respectively. For each patient subpopulation, antimicrobial resistance of <em>E. coli</em> to ampicillin, amoxicillin/clavulanic acid, cefotaxime, cefixime, and trimethoprim-sulfamethoxazole was more than 20%. Rates of <em>E. coli</em> resistance to ciprofloxacin were 36.7% in the adult subpopulation; 22.1% in the pregnant subpopulation; and 22.2% in the children and adolescents under 18 years of age subpopulation. The rate of extended-spectrum beta-lactamase production based on phenotypic test results was 29.6% in the adult subpopulation; 23.6% in the pregnant subpopulation and 33.3% in the children and adolescents under 18 years of age subpopulation.</p> <h3 id="conclusions">Conclusions.</h3> <p>In community-acquired UTIs the main clinical problem is the persistent high rate of <em>E. coli</em> resistance to cephalosporins, fluoroquinolones, aminopenicillins/beta-lactamase inhibitors, as well as the increase of the extended-spectrum beta-lactamases production. Remaining high <em>in vitro</em> activity of fosfomycin and nitrofurans allows to consider them as drugs of choice in uncomplicated lower urinary tract infections.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p318/ Thu, 14 Nov 2024 10:17:39 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p318/ <h3 id="objective">Objective.</h3> <p>To evaluate <em>in vitro</em> activity of various macrolide antibiotics against a current collection of clinical isolates of <em>Streptococcus pneumoniae</em> and <em>Streptococcus pyogenes</em> isolated from patients with community-acquired infections in different regions of the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 350 clinical isolates from patients with community-acquired infections, including 200 <em>S. pneumoniae</em> and 150 <em>S. pyogenes</em>, were included in the study. To further evaluate the <em>in vitro</em> activity of 16-member macrolides against erythromycin-resistant isolates (MIC ≥ 0.5 mg/L), a retrospective collection of 253 erythromycin-resistant <em>S. pneumoniae</em> and 112 <em>S. pyogenes</em> isolates was tested. Susceptibility to antimicrobials was determined by broth microdilution method in accordance with the recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST, v.14.0).</p> <h3 id="results">Results.</h3> <p>Resistant to 14- and 15-member macrolides erythromycin, clarithromycin, and azithromycin were 41.5%, 42% and 40.5% of <em>S. pneumoniae</em> isolates (MIC50/MIC90 values were 0.06/128, 0.03/128, and 0.¹²⁵&frasl;₁₂₈ mg/L, respectively). MIC50/MIC90 values for spiramycin and josamycin were 0.06/128 mg/L and ²⁵&frasl;₃₂ mg/L, respectively. When the previously used 1996 French Society for Microbiology (SFM) criteria (Ch, ≤ 1 mg/L; P, &gt; 4 mg/L) were applied, 70.5% of <em>S. pneumoniae</em> isolates could be considered as susceptible to spiramycin. MIC value ≥0.5 mg/L accounted for 31.5% of isolates for spiramycin and 48% for josamycin. Among the retrospective collection of erythromycin-resistant <em>S. pneumoniae</em> isolates, 64.0% of isolates could be considered as resistant to spiramycin using the old SFM interpretative criteria; 74.9% of isolates had spiramycin MIC ≥ 0.5 mg/L. Among the <em>S. pyogenes</em> isolates, 19.3%, 22%, and 26.7% were resistant to the 14- and 15-member macrolides erythromycin, clarithromycin, and azithromycin (MIC50/MIC90 0.03/1, 0.03/2, and 0.06/8 mg/L, respectively). MIC50/MIC90 values for the 16-member macrolides spiramycin and josamycin were 0.²⁵&frasl;₀.5 mg/L and 0.¹²⁵&frasl;₀.5 mg/L, respectively. When the 1996 SFM criteria (S – ≤ 1 mg/L; R – &gt; 4 mg/L) were applied, 94.7% of <em>S. pyogenes</em> isolates could be considered as susceptible to spiramycin; MIC values ≥ 0.5 mg/L had 15.3% of isolates for spiramycin and 16.5% for josamycin.</p> <h3 id="conclusions">Conclusions.</h3> <p>The 16-member macrolide spiramycin can retain <em>in vitro</em> activity against a significant proportion of <em>S. pneumoniae</em> and <em>S. pyogenes</em> isolates resistant to 14- and 15-member macrolides, which should be taken into account when choosing therapy for infections caused by these microorganisms.</p> http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p274/ Fri, 04 Oct 2024 10:10:33 +0000 http://cmac-journal.ru/en/publication/2024/3/cmac-2024-t26-n3-p274/ <h3 id="objective">Objective.</h3> <p>In 2023–2014, a significant increase in the incidence of pneumonia caused by <em>M. pneumoniae</em> has been reported in Russia and China. Despite being one of the primary causative agents of community-acquired lower respiratory tract infections in children, due to the difficulties in obtaining a culture of this pathogen, the amount of genomic data on <em>M. pneumoniae</em> is currently extremely limited, with fewer than 300 genomic sequences available, of which only 79 are complete. Until this study, no genomic data for isolates relevant to the Russian Federation were available.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Using biological material from patients with confirmed mycoplasma infection, cultures of <em>M. pneumoniae</em> were obtained, for which whole-genome sequencing was carried out, followed by assembly and annotation of the pathogen genome.</p> <h3 id="results">Results.</h3> <p>We have obtained and characterized three complete circular genome sequences of <em>M. pneumoniae</em>, first described for Russia. Utilizing all genomic sequences of <em>M. pneumoniae</em> available in public databases, we conducted a phylogenetic analysis as well as a comparative analysis of clinically significant genes, revealing previously undescribed mutations in cytoadherence proteins.</p> <h3 id="conclusions">Conclusions.</h3> <p>In this study, we characterized the first full genome sequences of <em>M. pneumoniae</em> isolated in the Russian Federation, as well as provided detailed methods for cultivating the pathogen and the data processing process, which can be used to further expand the amount of available data on the genetic structure of the pathogen.</p> http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p236/ Thu, 15 Aug 2024 15:29:14 +0000 http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p236/ <h3 id="objective">Objective.</h3> <p>To evaluate the dynamics of antimicrobial resistance of <em>Escherichia coli</em> isolates from the urine of patients hospitalized in medical institutions of Tashkent city from 2018 to 2021.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 1020 <em>E. coli</em> isolates from the urine of patients with clinical symptoms of urinary tract infections admitted to the reference laboratory of the Antimicrobial Resistance Research Center (ARRC) from three medical institutions in Tashkent city for the period 2018– 2021. Determination of sensitivity to 15 antimicrobial agents was carried out by disc-diffusion method in accordance with the guidelines of the European Committee for the Determination of Sensitivity to Antimicrobial Agents (EUCAST v.8-v.12, depending on the year of isolates isolation and testing).</p> <h3 id="results">Results.</h3> <p>A high level of resistance to aminopenicillins, including inhibitor-protected ones (88.0–91.1%), 3–4 generation cephalosporins (84.5–87.7%) and fluoroquinolones (74.2–81.8%) was detected. Carbapenems showed the highest activity among the tested antimicrobials: resistance to imipenem, meropenem and ertapenem was 0%, 0.8% and 18%, respectively. Notable increase in resistance to ampicillin and ceftazidime was found, but a consistently high level of resistance to piperacillin-tazobactam. A statistically significant increase (p &lt; 0.001) was found between 2018–2021 in resistance to the aminoglycoside antibiotics amikacin and gentamicin from 3.2% and 37.8% to 85.4% and 80.6%, respectively.</p> <h3 id="conclusions">Conclusions.</h3> <p>In our study, for most antibiotic groups, the level of resistance remained relatively stable from 2018 to 2021, except for an explosive increase in the frequency of resistance to aminoglycosides, as well as a further increase in resistance to ampicillin and ceftazidime. The need for monitoring and tracking of antibiotic pathogens when choosing treatment regimens for various infections is obvious.</p> http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p229/ Sat, 10 Aug 2024 10:24:03 +0000 http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p229/ <h3 id="objective">Objective.</h3> <p>To identify specific features of the clinical course of Congo-Crimean hemorrhagic fever (CCHF) in children in order to optimize early and differential diagnosis, management tactics and treatment of pediatric patients</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective analysis of 159 probable and confirmed cases of Congo-Crimean hemorrhagic fever was carried out in patients admitted to the infectious diseases departments of Shymkent, district hospitals of Turkestan region for the period 2013–2022, of which 39 (24.5%) were children aged 1 to 18 years.</p> <h3 id="results">Results.</h3> <p>Of the 39 cases of CCHF in children, 9 (23.07%) were reported as confirmed, 5 (12.8%) as probable and 25 (64.1%) as suspected cases. In the epidemiological history, tick bite was noted in 25 (64.1%) cases. The incubation period in children and adolescents ranged from 1 to 14 days, on average – 9–8 days. Two children developed a severe complication of CCHF – hemoperitoneum.</p> <h3 id="conclusions">Conclusions.</h3> <p>The probability of CCHF infection in children increases during the season of tick vector activity. The clinical picture of CCHF in children may be similar to manifestations of this infection in adults. Among the rare severe forms of CCHF, children may develop hemoperitoneum.</p> http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p215/ Sat, 10 Aug 2024 10:22:22 +0000 http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p215/ <h3 id="objective">Objective.</h3> <p>To determine the level of knowledge of doctors on the rational use of antimicrobial drugs in clinical practice and to compare with data of the previous stage of the study and results obtained from students in a parallel project.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A multicenter questionnaire survey of practitioners with analysis of results – stage of KANT project (full name of the project – «Physicians’ (Students’) knowledge in antimicrobials usage») conducted in 2020–2023.</p> <h3 id="results">Results.</h3> <p>A total of 336 participants were surveyed in 5 centers (10 Russian regions: Belgorod, Novosibirsk, Rostov, Voronezh, Lipetsk, Sakhalin, Primorsky, Krasnodar, and Krasnoyarsk regions, Republic of Tatarstan). The average level of correct answers (LCA) for the whole questionnaire was 47.5% (taking into account the extended analysis of sub-items questions No. 8 and 9 – 46.8%). Doctors showed the best results in answering questions about the time interval during which the effectiveness of antimicrobial therapy is evaluated (LCA – 84.2%); about choosing the most rational action if antimicrobial therapy (AMT) has a positive clinical effect, but requires a long course of therapy (LCA – 72.6%); selection of rational diagnostic/treatment action in the diagnosis of acute tonsillitis or pharyngitis, in a case where etiologic diagnosis is required (LCA – 63.1%). The worst results were recorded in answering to the following questions: indication of the antimicrobial drug of choice in the treatment of various infections (LCA – 29.1%); the choice of auxiliary drugs in addition to the justified appointment of antimicrobial drugs in the treatment of bacterial infections of the respiratory tract for the entire period of the disease or in certain phases (LCA – 26.6% – 35.1%); indication of a combination of antimicrobial drugs that is irrational to prescribe in clinical practice due to a similar mechanism and/or spectrum of activity against pathogens (LCA – 24.4%). Significant differences were found between centers in a number of questions, between physicians in KANT-III and KANT-IV projects (p &lt; 0.001), and between physicians and students in a parallel project (KANT-IV students, LCA – 42.6%, p &lt; 0.001).</p> <h3 id="conclusions">Conclusions.</h3> <p>An unsatisfactory level of physicians’ knowledge of AMT and choice of adjuvant agents, as well as appropriateness of antimicrobial combination was found. The authors believe there is a need for making more efforts in areas of increasing physicians’ compliance to clinical recommendations, expertise and quality control of pharmacotherapy, recruitment of clinical pharmacologists; to optimize the educational process in universities, to expand the scope and availability of additional educational programs within the system of continuous education, as well as to train physicians in using modern sources of scientific medical information.</p> http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p201/ Sat, 10 Aug 2024 10:17:56 +0000 http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p201/ <h3 id="objective">Objective.</h3> <p>To study epidemiology of resistance to macrolides and fluoroquinolones in Mycoplasmagenitalium isolated from pregnant women in Russia and Belarus.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 107 M. genitalium DNA samples isolated from pregnant women in Russia (n = 58) and Belarus (n = 49) was included in the study. In order to detect markers of macrolide or fluoroquinolone resistance, polymerase chain reaction in real time with the effect of quenching fluorescence of the probe by a primer was used. Confirmation of mutation type was performed using Sanger sequencing.</p> <h3 id="results">Results.</h3> <p>The prevalence of M. genitalium resistance mutations to macrolides in Russia (Tula, Smolensk) and Belarus (Vitebsk, Brest, Minsk) was 3.4% (²&frasl;₅₈) and 6.1% (³&frasl;₄₉), respectively. Markers of M. genitalium resistance to fluoroquinolones were detected in 5.2% (³&frasl;₅₈) of samples from Russia and 8.2% (⁴&frasl;₄₉) of samples from Belarus. The most common mutations associated with macrolide resistance were A2059G (n = 4), fluoroquinolone resistance – D84N (n = 3) and S80I (n = 3) (numbering according to <em>E. coli</em>).</p> <h3 id="conclusions">Conclusions.</h3> <p>The prevalence of M. genitalium resistance markers isolated in pregnant women highlights a need for regular macrolide and fluoroquinolone resistance surveillance.</p> http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p194/ Sat, 10 Aug 2024 10:15:46 +0000 http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p194/ <h3 id="objective">Objective.</h3> <p>To study the dynamics and molecular mechanisms of resistance of <em>Streptococcus agalactiae</em> strains isolated from pregnant women and newborns in St. Petersburg in 2010–2022.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The strains of <em>S. agalactiae</em> (n = 248) were obtained by analyzing the clinical material of pregnant women and newborns who were hospitalized at Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott in 2010–2011 and 2020–2022. Determination of susceptibility to antibacterial drugs was evaluated by disk diffusion method. The detection of resistance genes to macrolides and lincosamides (mef and ermB) was performed by real-time PCR using reagents &laquo;Resistom MLSB-Streptococcus&raquo; (Litech, Russia).</p> <h3 id="results">Results.</h3> <p>All isolates <em>S. agalactiae</em> (n = 248) were sensitive to penicillin and vancomycin. Compared to 2010–2011, the resistance of <em>S. agalactiae</em> to erythromycin increased from 18.4% to 42.1% and to clindamycin from 15.6% to 39.3%. Among <em>S. agalactiae</em> strains (n = 71) resistant to erythromycin and clindamycin, cMLSB phenotype was predominant (59.1%); iMLSB (31%) and M-phenotype (9.9%) were less common. The results of detection of genes encoding resistance to erythromycin and clindamycin showed that in 38 (53.5%) and 9 (12.7%) isolates of <em>S. agalactiae</em> resistance genes ermB and mefA were detected as one resistance determinant, respectively, association of two ermB/mefA genes was detected in 2 (2.8%) strains; resistance genes were not detected in 22 (31%) isolates.</p> <h3 id="conclusions">Conclusions.</h3> <p>Penicillin and vancomycin are effective drugs for the treatment and prevention of infections caused by <em>S. agalactiae</em>. The increase in resistance to macrolides and lincosamides reflects the global trend of increasing resistance to these antibiotics. Regular monitoring of antibiotic resistance of the pathogen is necessary to update the clinical recommendations.</p> http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p188/ Sat, 10 Aug 2024 10:13:31 +0000 http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p188/ <h3 id="objective">Objective.</h3> <p>To study the antimicrobial susceptibility profile of <em>Moraxella catarrhalis</em> isolates from different regions of Russia in 2010–2021.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 352 isolates of <em>M. catarrhalis</em> isolated in 11 cities of Russia (Volgograd, Irkutsk, Kazan, Kirov, Moscow, Murmansk, Perm, Seversk, Togliatti, Tomsk, and Ulan-Ude) in 2010–2021. Identification was done by MALDI-TOF mass spectrometry. Antimicrobial susceptibility testing was determined by broth microdilution method in accordance with the ISO 20776-1:2020. Interpretation of results was done in accordance with EUCAST guidelines (v.14.0).</p> <h3 id="results">Results.</h3> <p>Most of the isolates were isolated from respiratory specimens: 225 (63.9%) from sputum, 49 (13.9%) from nasal swabs, 41 (11.6%) from sinus aspirates, 17 (4.8%) from bronchoalveolar lavage, 8 (2.3%) from middle ear fluid, 6 (1.7%) from pharyngeal swabs, and 5 (1.4%) from conjunctival secretions. All tested isolates were susceptible to beta-lactams for which interpretive criteria have been established (amoxicillin-clavulanate, cefixime, ceftriaxone, cefuroxime). The susceptibility to clarithromycin and azithromycin was 99.7% and 100%, respectively. Ciprofloxacin, levofloxacin and moxifloxacin were active against 98.9%, 99.2% and 99.7% of isolates tested, respectively. Susceptibility to tetracycline was 99.7% and to trimethoprim-sulfamethoxazole was 99.4% (92% of isolates susceptible, 7.4% – susceptible at increased exposure).</p> <h3 id="conclusions">Conclusions.</h3> <p>In the Russian Federation there is a favorable situation regarding the susceptibility of <em>M. catarrhalis</em> to antimicrobials. Amoxicillin-clavulanic acid, cefixime, ceftriaxone, azithromycin, clarithromycin, ciprofloxacin, levofloxacin, moxifloxacin and tetracycline retain high <em>in vitro</em> activity</p> http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p141/ Sat, 10 Aug 2024 10:00:06 +0000 http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p141/ <h3 id="objective">Objective.</h3> <p>To study the etiology of community-acquired pneumonia (CAP) in adult hospitalized patients after the COVID-19 pandemic.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The prospective multicenter study included patients 18 years and older with confirmed diagnosis of CAP admitted to 6 hospitals in different regions of Russia from July to November 2023. Etiology was confirmed by respiratory samples (sputum, tracheal aspirate) culture, blood culture (severe cases), and urinary antigen tests (<em>Legionella pneumophila</em> serogroup 1, <em>Streptococcus pneumoniae</em>). <em>Mycoplasma pneumoniae</em>, Chlamydia pneumoniae, and common respiratory viruses were identified using the real-time polymerase chain reaction (PCR) in respiratory samples. Qualitative PCR for <em>S. pneumoniae</em> and <em>Haemophilus influenzae</em> DNA tests were also applied.</p> <h3 id="results">Results.</h3> <p>Altogether 152 patients were enrolled, and significant CAP pathogens were identified in 96 (63%) cases; the median age of patients with verified etiology of CAP was 45 [34.8; 66] years, comorbidity index was 0.5 (0; 3.0) points. The most frequently detected pathogens were <em>M. pneumoniae</em> – 42 (44%), rhinovirus – 23 (24%), <em>S. pneumoniae</em> – 17 (18%) and SARS-CoV-2 – 13 (14%). Coinfection was registered in 22% of cases, the most common associations were <em>M. pneumoniae</em> + rhinovirus – 5 (3.3%), <em>S. pneumoniae</em> + rhinovirus – 3 (2%). Pneumococcal bacteremia was detected in 1 patient. In most patients CAP was non-severe; 17 (18%) patients required admission to the ICU. Hospital mortality was 7%.</p> <h3 id="conclusions">Conclusions.</h3> <p><em>M. pneumoniae</em>, respiratory viruses (mainly rhinovirus and SARS-CoV-2), and <em>S. pneumoniae</em> were the predominant CAP pathogens in hospitalized adults with CAP in the first months after the COVID-19 pandemiс. The use of an integrated approach to etiological diagnosis can significantly increase the proportion of patients with an established etiology of CAP.</p> http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p124/ Sat, 10 Aug 2024 09:53:43 +0000 http://cmac-journal.ru/en/publication/2024/2/cmac-2024-t26-n2-p124/ <h3 id="objective">Objective.</h3> <p>To determine etiological structure of infections in the surgical intensive care unit (ICU), identify the most common mechanisms of antibiotic resistance of leading pathogens, and develop recommendations for optimizing antimicrobial therapy in the ICU at the present stage.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A prospective observational study was conducted in the surgical ICU of the Moscow City Clinical Center &laquo;Kommunarka&raquo; from September 2022 to February 2024. The subjects of observation were 2120 patients treated in the unit. Microbiological examination of patients&rsquo; biological fluids was carried out in accordance with approved methodological guidelines. The results of determining the susceptibility of isolated pathogens were interpreted based on the EUCAST v14.0 criteria. Automatic bacteriological analyzers, MALDI-TOF mass spectrometry for pathogen identification, PCR and immunochromatographic methods for determining resistance mechanisms were used. To determine the etiological structure of infections in hospitalized patients, only original isolates were considered, following the principle of &laquo;one patient – one microbe.&raquo;</p> <h3 id="results">Results.</h3> <p>A total of 1213 bacterial and 53 fungal pathogens were isolated from 394 patients. The leading pathogens were <em>Klebsiella pneumoniae</em> (18.5%), <em>Acinetobacter baumannii</em> (13.4%), and <em>Pseudomonas aeruginosa</em> (9.5%). Resistance to meropenem was 83.0% for <em>K. pneumoniae</em>, 97.4% for <em>A. baumannii</em>, and 81.5% for <em>P. aeruginosa</em>. The highest <em>in vitro</em> activity against <em>Enterobacterales</em> was exhibited by ceftazidime-avibactam (79.2% of susceptible isolates), while against <em>A. baumannii</em> and <em>P. aeruginosa</em>, it was colistin (98.6% and 90.6% of susceptible isolates, respectively). The genetic mechanisms of carbapenem resistance in <em>Enterobacterales</em> were identified: production of NDM (26.3%), OXA-48 (29.6%), and KPC (44.1%) carbapenemases.</p> <h3 id="conclusions">Conclusions.</h3> <p>The predominant pathogens of infections in surgical ICU patients are gram-negative bacteria with a high level of antibiotic resistance, including carbapenem-resistant <em>Enterobacterales</em>, whose resistance is due to the production of carbapenemases of various molecular classes. An increase in the prevalence of the serine carbapenemase KPC, previously atypical for the Russian Federation, has been noted. Currently, for infections caused by <em>Enterobacterales</em> producing serine carbapenemases, ceftazidime-avibactam can be recommended, and in the case of metallo-beta-lactamase production by <em>Enterobacterales</em>, a combination of ceftazidime-avibactam with aztreonam. For infections caused by <em>A. baumannii</em> and <em>P. aeruginosa</em>, regimens including polymyxins are indicated.</p> http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p98/ Thu, 09 May 2024 10:44:14 +0000 http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p98/ <h3 id="objective">Objective.</h3> <p>The aim of the study was to develop gradient diffusion strips with substances capable of potentiating the action of antibiotics for the treatment of infections caused by multidrug-resistant strains of <em>K. pneumoniae</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The substances azidothymidine and baicalin were used to evaluate the joint action of combinations of antibiotics with substances that potentiate their action. Determination of susceptibility to combinations of antibiotics (gentamicin, cefotaxime, ciprofloxacin and chloramphenicol) with the listed substances was carried out by a modified gradient-diffusion method (cross-test). We used gradient diffusion strips, which was made in the Saint-Petersburg Pasteur Institute. We investigated clinical multidrug-resistant <em>K. pneumoniae</em> strains (n = 20). The result of the joint action of a combination of two compounds was assessed by calculating the fractional inhibitory concentrations ΣFIC.</p> <h3 id="results">Results.</h3> <p>The values of MIC decreased eightfold when azidothymidine was combined with gentamicin and two times when combined with ciprofloxacin. MIC values were not reduced by the combination of azidothymidine with cefotaxime or chloramphenicol. It has been established that azidothymidine has antibacterial activity against strains of <em>K. pneumoniae</em>: MIC50 – 1 μg/ml and MIC90 – 2 μg/ml. The MIC50 and MIC90 values for baicalin were &gt; 256 μg/ml. A synergistic antibacterial effect was detected when azidothymidine was combined with gentamicin (ΣFIC 0.33–0.50). An additive effect (ΣFIC 0.65–0.84) was detected when azidothymidine was combined with ciprofloxacin. Baikalin reduced the MIC value of cefotaxime by half, and the MIC50 values for gentamicin also decreased by half. Baicalin did not affect the susceptibility of multidrug-resistant <em>K. pneumoniae</em> strains to ciprofloxacin and chloramphenicol. Synergism was detected in the combination of baicalin and cefotaxime (ΣFIC 0.52 – 0.75 – additive effect).</p> <h3 id="conclusions">Conclusions.</h3> <p>The development of gradient diffusion strips with azidothymidine and baicalin makes it possible to simplify methods for assessing the joint action of combinations of these substances with antibiotics and to avoid time-consuming preparatory steps. Our study demonstrated that azidothymidine exhibits synergistic activity in combination with gentamicin and ciprofloxacin and baicalin – in combination with cefotaxime. Further studies are needed to evaluate the potential use of these combinations in practical healthcare.</p> http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p87/ Thu, 09 May 2024 10:42:38 +0000 http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p87/ <h3 id="objective">Objective.</h3> <p>To determine the level of basic knowledge of 5–6-year medical students in the issues of appropriate antimicrobial therapy.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A multicenter questionnaire survey with analysis of results – stage of KANT project (full name of the project – «Physicians’ (Students’) knowledge in antimicrobials usage») conducted in 2020-2023.</p> <h3 id="results">Results.</h3> <p>A total of 277 students in 6 regions of Russia were surveyed. The average level of correct answers for the whole questionnaire amounted to 42.2%, taking into account the extended analysis of sub-items questions #8,9 – 42.6%. The respondents were best able to answer the questionnaire questions about the choice of time interval during which the effectiveness of antimicrobial therapy is assessed (average level of completeness of the answer – 90.6%); the choice of the most rational action when diagnosing acute tonsillitis or pharyngitis at the appointment (average level of completeness of the answer – 57.8%); indication of the regimen of different AMD (average level of completeness of the answer – 55.2%). The worst results were recorded when answering the following questions: justification of the situation of prolongation of antimicrobial therapy (AMT) for more than 5-7 days in a patient with positive clinical dynamics in the treatment of outpatient pneumonia (average level of completeness of the answer – 19.5%), indication of AMD of choice in the therapy of various infections (average level of completeness of the answer – 22.9%), prescription of auxiliary drugs to the justified prescription of AMD in the treatment of respiratory tract infections (average level of completeness of the answer – 21.3%).</p> <h3 id="conclusions">Conclusions.</h3> <p>Having researched the results of this study, we can conclude that the level of knowledge of senior medical students in rational antibiotic therapy is quite low. In this regard, according to the authors, it is necessary to allocate an additional number of academic hours in the disciplines of &laquo;Pharmacology&raquo;, &laquo;Clinical Pharmacology&raquo;, specialized therapeutic disciplines, to optimize the educational program, as well as to provide students with modern sources of information that relate to the topic of rational antimicrobial therapy.</p> http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p79/ Thu, 09 May 2024 10:40:34 +0000 http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p79/ <h3 id="objective">Objective.</h3> <p>The development of a method for identifying frequent genetic determinants of Mycobacterium leprae clinical isolates resistance to three groups of antimicrobial drugs: dapsone, rifampicin and fluoroquinolones using SNaPshot technique.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included M. leprae clinical isolates obtained from skin biopsies of patients undergoing leprosy treatment at the Sergiev Posad branch of the State Research Center of Dermatovenereology and Cosmetology of the Ministry of Health of Russia. One of the patients has the diagnosis ‘Leprosy, lepromatous type’, the second one has the diagnosis ‘Leprosy. Multibacterial leprosy, borderline’. The selection of oligonucleotide sequences and hybridization probes for M. leprae drug resistance-determining genomic regions PCR was carried out according to information from the BLAST, the synthesis was performed by ‘Synthol’ LLC (Russia). The first PCR was carried out using the QIAGEN Multiplex PCR kit (Germany), and subsequent SNP analysis using the “SNaPshot” kit at the ABI 3130 Genetic Analyzer. The data obtained were depicted using Peak Scanner Software.</p> <h3 id="results">Results.</h3> <p>A method of six most frequent genetic determinants of antimicrobial resistance of M. leprae identification in patient skin biopsies was developed. Drug resistance of the disease is caused by the M. leprae genome mutations located in drug resistance-determining regions in the genomic loci: folP1 for dapsone, rpoB for rifampicin and gyrA for fluoroquinolones resistance. The SNP polymorphisms stipulated drug resistance as a result of changes in the amino acid sequence of the transcribed protein, are determined in following M. leprae genome regions: rpoB: D441, H451, S456; gyrA: A91; folp1: T53, T55. The technique is SNaPshot determination of nine SNP performed on DNA isolated from the patient’s biological material. The control reaction confirming the presence of M. leprae DNA in the sample is PCR using primers to the non-coding repeat element of the leprosy genome RLEP. The pilot application of the technique developed to the samples of clinical material from patients showed the absence of M. leprae resistance determinants to antimicrobial drugs most often used to treat leprosy.</p> <h3 id="conclusions">Conclusions.</h3> <p>The use of a system for rapid identification of leprosy clinical isolates resistance to antimicrobial therapy will personalize the provision of medical care and provide the opportunity to select the optimal chemotherapy regimen, which will lead to increased efficiency of treatment of the disease.</p> http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p67/ Thu, 09 May 2024 10:38:59 +0000 http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p67/ <h3 id="objective">Objective.</h3> <p>To study the prevalence and mechanisms of antibiotic resistance, including carbapenemase production, in clinical isolates of <em>Klebsiella pneumoniae</em> and <em>Escherichia coli</em> isolated in different regions of Russia as part of the sentinel multicenter surveillance study in 2020–2021, and to explore the population structure of <em>K. pneumoniae</em> and the impact of “high-risk clones” on antibiotic resistance.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Consecutive, non-duplicate isolates of <em>K. pneumoniae</em> (n = 2503) and <em>E. coli</em> (n = 2055) isolated from various specimens (blood, cerebrospinal fluid, respiratory samples, urine, wound secretions, etc.) of hospitalized patients with clinical signs of infection in 55 hospitals of 29 cities of Russia were studied. Species identification of isolates was performed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibilities were determined by serial broth microdilution or, in the case of fosfomycin, by agar dilution method, and results were interpreted according to EUCAST v13 MIC breakpoints. Carbapenemase production was determined phenotypically by carbapenem inactivation method (CIM), the presence of genes of the most common serine carbapenemases (KPC, OXA-48) and metallo-β-lactamases (VIM, IMP, NDM) was determined by real-time PCR. <em>K. pneumoniae</em> clinical isolates were genotyped and assigned to the known clonal complexes (CC) and sequence types (ST) using SNP typing and multilocus sequencing typing (MLST) methods. K- and O-serotypes, acquired resistance and virulence genes, and plasmids carrying these genes were characterized using whole-genome sequencing of selected isolates (n = 215).</p> <h3 id="results">Results.</h3> <p>The resistance rates of nosocomial/community-acquired isolates of <em>K. pneumoniae</em> were as follows: amoxicillin-clavulanate – 88.⁶³&frasl;₅₇.99%, piperacillin-tazobactam – 82.⁹²&frasl;₄₅.49%, cefotaxime – 87.⁷⁴&frasl;₅₆.97%, ceftazidime – 84.⁷⁶&frasl;₅₃.07%, cefepime – 81.⁴³&frasl;₄₉.18%, aztreonam – 1.⁶³&frasl;₅₃.28%, ceftazidime-avibactam – 30, ⁸⁸&frasl;₉.22%, ceftolozan-tazobactam – 70.06/31.35%, ertapenem – 72.¹⁰&frasl;₂₈.69%, meropenem – 49.⁶⁰&frasl;₁₅.16%, imipenem – 44.⁵⁴&frasl;₁₃.73%, gentamicin – 60.⁸²&frasl;₃₀.33%, amikacin – 42.06/17.21%, ciprofloxacin – 85.¹⁰&frasl;₄₉.39%; trimethoprimsulfamethoxazole – 74.³⁸&frasl;₄₈.16%, colistin – 5.⁹⁶&frasl;₂.25%. The resistance of nosocomial/outpatient isolates of <em>E. coli</em> were: ampicillin – 84.⁹³&frasl;₆₇.67%, amoxicillin-clavulanate – 57.³⁷&frasl;₃₉.73%, piperacillin-tazobactam – 19.⁴⁸&frasl;₈.70%, cefotaxime – 63.⁸³&frasl;₃₄.19%, ceftazidime – 45.³²&frasl;₂₀.34%, cefepime – 35.⁹⁵&frasl;₁₆.61%, aztreonam – 51.⁷⁸&frasl;₂₆.11%, ceftazidime-avibactam – 5.⁷¹&frasl;₀.80%, ceftolozane-tazobactam – 11, ⁹⁵&frasl;₂.22%, ertapenem – 8.¹⁸&frasl;₁.42%, meropenem – 5.¹⁷&frasl;₀.53%, imipenem – 4.⁹⁵&frasl;₀.36%, gentamicin – 24.⁵⁴&frasl;₁₃.68%, amikacin – 5.⁴⁹&frasl;₁.42%, ciprofloxacin – 54, ¹⁴&frasl;₃₂.50%, trimethoprim-sulfamethoxazole – 52.²¹&frasl;₃₈.54%, fosfomycin – 2.⁴⁸&frasl;₁.43%, colistin – 1.⁶⁰&frasl;₁.07%, tigecycline – 6.³⁵&frasl;₃.11%. The frequency of carbapenemase production among <em>K. pneumoniae</em> nosocomial isolates was 65.32% (OXA-48 – 40.75%, NDM – 30.28%, KPC – 8.74%, OXA-48 + NDM – 10.62%, OXA-48 + KPC – 2.98%, NDM + KPC – 0.45%, OXA-48 + NDM + KPC – 0.20%). More than 70% of nosocomial isolates of <em>K. pneumoniae</em> belonged to only 7 major genetic lineages known as “high-risk international clones”: CC395 – 37.40%, CC23 – 9.59%, CC307 – 8.64%, CC147 – 7.61%, CC15 – 2.95%, CC258 – 2.92%, and CC11 – 2.41%. The population of community-acquired <em>K. pneumoniae</em> was characterized by significantly greater genetic diversity (Simpson diversity index: D = 0.919; 95% CI: 0.904 to 0.933) compared with the population of nosocomial strains (Simpson diversity index: D = 0.815; 95% CI: 0.802 to 0.827). Strains of the “hypervirulent” genetic lineage of <em>K. pneumoniae</em> CC23 were more common in community-acquired infections.</p> <h3 id="conclusions">Conclusions.</h3> <p>The extremely high frequency of resistance to cephalosporins in <em>K. pneumoniae</em> (&gt; 80%) and <em>E. coli</em> (&gt; 60%), as well as the high frequency of combined resistance to aminoglycosides and fluoroquinolones precludes their empirical use for the treatment of serious nosocomial infections caused by these pathogens. <em>K. pneumoniae</em> shows a rapid increase in resistance to carbapenems, mainly due to the spread of carbapenemases of three major groups: OXA-48, NDM and KPC. The overall increase in the frequency of carbapenemase production is accompanied by the growing diversity of carbapenemases, the increasing prevalence of strains producing NDM and KPC enzymes and those co-producing multiple carbapenemases simultaneously. In community-acquired infections, the high prevalence of resistance to cephalosporins in <em>E. coli</em> (&gt; 30%) and <em>K. pneumoniae</em> (&gt; 50%) remains the most important problem.</p> http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p31/ Thu, 09 May 2024 10:33:13 +0000 http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p31/ <h3 id="objective">Objective.</h3> <p>To determine the minimum inhibitory concentrations of thiamphenicol and thiamphenicol glycinate acetylcysteinate against clinically significant microorganisms and determine their efficacy against microbial biofilms.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>This study included 48 clinical strains isolated from the sputum of patients with respiratory tract infections (16 <em>S. pneumoniae</em>, <em>K. pneumoniae</em> and <em>S. aureus</em> strains). Antimicrobial susceptibility testing was performed using broth microdilution method. Biofilm formation culturing with antibiotics, N-acetylcysteine and their combinations was assessed in Mueller-Hinton broth and brain heart broth in 96-well plates. Biofilms are fixed with 2,5% glutaraldehyde solution, stained with 0,25% crystal violet solution, which is extracted by 33% acetic acid solution.</p> <h3 id="results">Results.</h3> <p>The MIC of thiamphenicol and thiamphenicol glycinate acetylcysteinate (in terms of thiamphenicol) were the same for 87,5% of strains. Thiamphenicol and thiamphenicol glycinate acetylcysteinate have been confirmed high antimicrobial activity against <em>S. pneumoniae</em> strains (MIC50 0,5 mg/l, MIC90 1-2 mg/l). Cultivation with chloramphenicol, thiamphenicol, thiamphenicol glycinate acetylcysteinate, combination of chloramphenicol and thiamphenicol with N-acetylcysteine contributed to significant reduction in the optical density of <em>S. pneumoniae</em> biofilms. Thiamphenicol increased biofilm formation in some resistant <em>S. aureus</em> and <em>K. pneumoniae</em>. Combination based on N-acetylcysteine neutralized this effect.</p> <h3 id="conclusions">Conclusions.</h3> <p>Potentiation of antibacterial activity of thiamphenicol by N-acetylcysteine against <em>S. pneumoniae</em> biofilms has been shown.</p> http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p4/ Thu, 09 May 2024 10:23:55 +0000 http://cmac-journal.ru/en/publication/2024/1/cmac-2024-t26-n1-p4/ <h3 id="objective">Objective.</h3> <p>To study virulence genes in <em>E. faecium</em> and <em>E. faecalis</em> isolated from the blood cultures of patients with hematological diseases.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Virulence genes were studied in <em>E. faecium</em> and <em>E. faecalis</em> strains isolated from blood culture from hematological patients in four Russian hospitals (2002–2020). Susceptibility to vancomycin was determined by broth microdilution method (CLSI, 2022). Virulence genes (esp, hyl, asa1, cylA and gelE) in <em>E. faecium</em> and <em>E. faecalis</em> as well as vancomycin resistance genes (vanA, vanB and vanD) in <em>Enterococcus</em> spp. were detected by multiplex PCR.</p> <h3 id="results">Results.</h3> <p>A total of 551 <em>Enterococcus</em> spp. strains were studied, of them 440 (79.9%) were <em>E. faecium</em> and 111 (20.1%) <em>E. faecalis</em>. Resistance to vancomycin was detected in 86 (19.5%) <em>E. faecium</em>, of them 62 (72.1%) carried vanA and 24 (27.9%) vanB genes. One (1.1%) of 111 <em>E. faecalis</em> was vancomycinintermediate (MIC 16 μg/ml) with vanD gene. Virulence genes were detected in 86.2% of <em>Enterococcus</em> spp., significantly more often among <em>E. faecalis</em> (95.5%) compared to <em>E. faecium</em> (83.9%, p = 0.003). The predominant genes in <em>E. faecium</em> were esp (70.2%) and hyl (52.1%), the detection of the asa1, cylA and gelE genes was minimal. Other genes dominated in <em>E. faecalis</em>: gelE (66.7%), asa1 (65.8%), cylA (36.9%). Statistically significant differences between <em>E. faecium</em> and <em>E. faecalis</em> were determined for all studied virulence genes (p &lt; 0.0001). A combination of three or more virulence genes was detected significantly more often among <em>E. faecalis</em> in comparison with <em>E. faecium</em> (45% vs. 2.5%, p &lt; 0.0001), whereas the presence of one gene or their absence prevailed in <em>E. faecium</em> (40.2% vs. 17.1%, p &lt; 0.0001; 16.1% vs. 4.5%, p = 0.003, respectively). When comparing the two study periods (2002–2010 and 2011–2020), <em>E. faecalis</em> showed a significant increase in the proportion of strains with a combination of three or more virulence genes from 33.3% to 55% (p = 0.03), in <em>E. faecium</em> – with one virulence gene (from 31.7% to 46.3%, p = 0.002) and no genes (from 6.6% to 23%, p &lt; 0.0001).</p> <h3 id="conclusions">Conclusions.</h3> <p>Differences in the frequency of detection of virulence genes and their spectrum have been identified between <em>E. faecium</em> and <em>E. faecalis</em> strains. Virulence genes are significantly more often detected in <em>E. faecalis</em> with a predominance of combinations of three or more genes.</p> http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p428/ Fri, 12 Jan 2024 14:13:41 +0000 http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p428/ <h3 id="objective">Objective.</h3> <p>To develop the method for determining the viability of M. leprae using polymerase chain reaction to evaluate the effectiveness of treatment.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>54 scarifications and 10 biopsies of the skin of patients with leprosy were studied. Ribosomal 16S rRNA genes were used as a target.</p> <h3 id="results">Results.</h3> <p>The high sensitivity and specificity of the developed real-time reverse transcription PCR method was established. M. leprae were detected on average 2 times more often by RT-PCR compared with the bacterioscopy method both before treatment and after its six-month course (p &lt; 0.05).</p> <h3 id="conclusions">Conclusions.</h3> <p>The developed method for determining the viability of M.leprae using reverse transcription PCR allows using a personalized approach to evaluating the effectiveness of antimycobacterial treatment in patients with leprosy.</p> http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p421/ Fri, 12 Jan 2024 14:11:34 +0000 http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p421/ <h3 id="objective">Objective.</h3> <p>To conduct a comparative evaluation of the results of phenotypic and molecular genetic methods for testing drug resistance of <em>Mycobacterium tuberculosis</em> isolated from bone biopsies of patients with tuberculous spondylitis.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective cohort study was conducted on the case histories of patients diagnosed with tuberculous spondylitis who underwent surgical treatment in the period from 2016 to 2021. The main study subject was surgical material. Antimicrobial resistance patterns of MBT isolates was performed using phenotypic and molecular genetic methods.</p> <h3 id="results">Results.</h3> <p>The vast majority of <em>Mycobacterium tuberculosis</em> isolates possess at least multidrug-resistance (MDR): 92 of 104 isolates (88.5%) according to phenotypic methods, and 192 of 274 DNA samples (70.1%) according to molecular methods. For rifampicin, isoniazid and ofloxacin the results of phenotypic and molecular methods matched in 92.7%, 97.9%, and 92.6% of cases, respectively; for levofloxacin, moxifloxacin and kanamycin – in 78.3%, 77.1%, and 73.1% of cases; , for amikacin and capreomycin – only – in 52.2% and 57.7% of cases, respectively. For rifampicin and isoniazid, the dominant mutations associated with resistance were: serine replacement for leucine in the 531 codon of the rpoB gene for rifampicin and serine replacement for threonine in the 315 codon of the katG gene for isoniazid.</p> <h3 id="conclusions">Conclusions.</h3> <p>Data on the presence of mutations associated with resistance to rifampicin (rpoB gene), isoniazid (katG gene) and aminoglycosides/capreomycin (rrs gene) can be used when prescribing chemotherapy regimens. The presence of mutations associated with MBT resistance to fluoroquinolones and aminoglycosides/capreomycin (eis gene) is not always accompanied by phenotypic manifestation of resistance. For these antimicrobials it is necessary to confirm resistance by phenotypic methods.</p> http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p415/ Fri, 12 Jan 2024 14:10:16 +0000 http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p415/ <h3 id="objective">Objective.</h3> <p>To study significance of herpesviruses in the development of infectious complications in patients after heart transplantation based on the detection of markers of herpesvirus infections.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The paper presents the results of a comprehensive examination for markers (HVI) of patients who underwent orthotopic heart transplantation at the V.I. Shumakov National Medical Center of Transplantology and Artificial Organs (Moscow). A total of 86 patients were observed. To establish the etiological diagnosis of infectious complications, all the blood serum and blood cell samples were analyzed for markers of herpesvirus infections. The titers of IgM and IgG antibodies to herpesviruses (HSV1, HSV-2, EBV, CMV and HCV-6) in blood serum were determined using enzyme-linked immunoassay. Indirect immunofluorescence was used to detect herpesviruses and their antigens in peripheral blood leukocytes. Early CMV and HCV-6 antigens as well as reproduction of HSV and EBV were detected by a rapid cultural method.</p> <h3 id="results">Results.</h3> <p>There was a wide prevalence of herpesviruses in the studied groups. It was shown that in all groups of patients with reduced immunity, herpesviruses always manifested themselves as mixed infections.</p> <h3 id="conclusions">Conclusions.</h3> <p>The study gives grounds to carry out laboratory diagnostics for all patients in order to differentiate the types of herpes viruses and the degree of their activity in order to identify activation and relief of infectious processes caused by herpes viral infections.</p> http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p408/ Fri, 12 Jan 2024 14:08:14 +0000 http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p408/ <h3 id="objective">Objective.</h3> <p>To compare results of microbiological examination obtained on rapid automated system with semiquantitative plate culture to assess possibility and necessity of using the system in urine examination.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 231 urine samples collected from February to July 2023 from patients at Lomonosov Moscow State University Medical Research and Educational Center. The samples were cultured according to the standards of urine microbiological examination using chromogenic media and using an automatic HB&amp;L system (Alifax, Italy) for 4 h. 30 min. to detect bacteriuria of 102 CFU/ ml or more and residual antimicrobial activity. When microbial growth was detected in the analyzer, extraction of microorganisms was performed on the same day for accelerated identification. Identification was performed by MALDI-TOF mass spectrometry.</p> <h3 id="results">Results.</h3> <p>According to the plate culture method, 160 positive samples were obtained. A total of 273 isolates were isolated, the predominant microorganisms were <em>E. faecalis</em> (22.3%) and <em>E. coli</em> (19.8%), a significant part was composed of atypical pathogens for UTI and normobiota (33.7%). According to the rapid automated system, only in 100 samples the growth of microorganisms was detected, in 4 cases the positive result obtained by the automatic system was not confirmed by growth on chromogenic media. Thus, 64 of the 160 positive cultures were not detected using the automated system, and 14 of those ones was <em>E. coli</em>. Residual antimicrobial activity was detected in 104 samples, including 43 of 64 false-negative culture results using the automated system. Rapid identification was performed on 57 samples, a microbial identification result was obtained in 49 of them. Complete or partial match between the results of rapid identification and classical methods was obtained for 48 samples. In all cases, when rapid identification was performed for a sample with monoculture, the results of two methods were identical.</p> <h3 id="conclusions">Conclusions.</h3> <p>An overall sensitivity and specificity of the culture method using an automatic system were 60% and 94.4%, respectively. Sensitivity for samples containing <em>E. coli</em> was 74.1%, and for their isolation in monoculture – 87.5%.</p> http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p401/ Fri, 12 Jan 2024 14:06:30 +0000 http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p401/ <h3 id="objective">Objective.</h3> <p>To assess the effects of chromosomal mutations on emergence of cefiderocol resistance among <em>Pseudomonas aeruginosa</em> clinical isolates.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Study design purported to compare the characteristics of phenotypic antibiotic resistance and chromosomal mutations of <em>P. aeruginosa</em> strains of a common origin possessing different resistance levels to cefiderocol. Two <em>P. aeruginosa</em> isolates from the sputum of a patient with cystic fibrosis who had not previously received cefiderocol were analyzed. Species identification was performed using an MALDI-TOF MS instrument and whole genome sequencing (WGS) data obtained from the MGISEQ-2000 platform. Antibiotic resistance was estimated based on minimum inhibitory concentration (MIC) testing. Plasmid-borne resistance genes and mutations in chromosomal genes associated with cefiderocol resistance were revealed based on WGS data.</p> <h3 id="results">Results.</h3> <p>Both <em>P. aeruginosa</em> isolates had the same antibiotic MIC values excluding meropenem and cefiderocol MIC values. Cefiderocol MICs were significantly different between the two strains corresponding to the resistant clinical category for one isolate and to the susceptible category for another one. Both strains belonged to 2554 sequence type. Eight potentially significant mutations in iron-uptake genes and genes associated with beta-lactam resistance were detected in the genome of the cefiderocol-resistant isolate, which were absent in the cefiderocol-susceptible strain. Cefiderocol resistant isolate harbored frameshift mutations in pirA, pirR and piv and nonsynonymous mutations in pfeA, cirA, iutA, pbpА and pchD.</p> <h3 id="conclusions">Conclusions.</h3> <p>Cefiderocol resistance can emerge among <em>P. aeruginosa</em> isolates which were not exposed to cefiderocol as the phenomenon of cross-resistance. Resistance to cefiderocol can be conferred not by a single mutation, but by a combination of chromosomal gene alterations.</p> http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p395/ Fri, 12 Jan 2024 14:02:19 +0000 http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p395/ <h3 id="objective">Objective.</h3> <p>To assess the dynamics of antimicrobial drug consumption in the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Data on antimicrobials for systemic use (ATC class J01) sales for the period 2008–2022 in the hospital and outpatient segment were downloaded from the IQVIA database. The absolute quantities of purchased antimicrobials were transferred to the defined daily doses (DDD) separately for the outpatient and hospital segments for each year of observation.</p> <h3 id="results">Results.</h3> <p>Over the period 2008-2022 there was an increase in antimicrobials consumption from 9.7 to 14.2 DDDs per 1000 inhabitants/day with a transient rise of up to 18.7 DDDs per 1000 inhabitants/day in 2020. In the outpatient segment, antimicrobials consumption was increased from 9.7 to 12.04 DDDs per 1000 population/day (a transient rise to 15.6 DDDs in 2020), and in the inpatient segment from 266.3 to 412.2 DDDs per 100 bed-days, respectively. When analyzing antimicrobials by access group (WHO classification AWaRe), there was a decrease in consumption «Access» group antimicrobials from 62% to 45%, an increase of «Watch» group antimicrobials from 38% to 63.4% and «Reserve» antimicrobials from 0.005% to 1.6%.</p> <h3 id="conclusions">Conclusions.</h3> <p>The increase in consumption of «Watch» group antimicrobials requires effective use control measures to be implemented at both outpatient and inpatient medical care settings at the national level.</p> http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p372/ Fri, 12 Jan 2024 13:58:08 +0000 http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p372/ <h3 id="objective">Objective.</h3> <p>To determine <em>in vitro</em> activity of oral III generation cephalosporin cefpodoxime against clinical isolates of <em>Haemophilus influenzae</em>, <em>Streptococcus pneumoniae</em> and <em>Streptococcus pyogenes</em> isolated from patients with community-acquired respiratory tract infections in different regions of the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included isolates of bacterial pathogens of community-acquired respiratory tract infections isolated from outpatients and hospitalized patients in different regions of the Russian Federation. A total of 558 isolates were included in the study, including 184 isolates of <em>H. influenzae</em>, 186 isolates of <em>S. pneumoniae</em> and 188 isolates of <em>S. pyogenes</em>. Species identification was performed using the MALDI-TOF mass spectrometry (Bruker Daltonics, Germany), for <em>S. pneumoniae</em> identification was also performed taking into account the morphology of colonies on blood agar, the presence of α-hemolysis, negative catalase reaction, sensitivity to optochin and positive results of latex-agglutination using DrySpot kit (OXOID, UK). Antimicrobial susceptibility to cefpodoxime and comparative antimicrobials was determined using broth microdilution method; interpretation of susceptibility testing results was performed in accordance with the recommendations of EUCAST, v.13.0. Data analysis and visualization were performed using the online platform AMRcloud.</p> <h3 id="results">Results.</h3> <p>Despite the generally low incidence of antibiotic resistance in the tested <em>H. influenzae</em> isolates, cefpodoxime, to which all tested isolates were susceptible, was superior to all other oral antibiotics in terms of <em>in vitro</em> activity: aminophenocillins (R – 8.7%), amoxicillin/clavulanate (R – 1.1%), co-trimoxazole (R – 31.5%), levofloxacin (R – 3.8%), moxifloxacin (R – 3.8%), tetracycline (R – 11%), cefixime (R – 2.2%), ceftibuten (R – 3.3%). Among the studied <em>S. pneumoniae</em> isolates, 81.7% were susceptible to cefpodoxime. All isolates resistant to penicillin, amoxicillin and ceftriaxone were also resistant to cefpodoxime. Cefpodoxime was inferior to levofloxacin (R – 0%), moxifloxacin (R – 0%), linezolid (R – 0%), vancomycin (R – 0%), ertapenem (R – 8.6%), ceftaroline (R – 2.3%), and chloramphenicol (R – 3.2%) in terms of <em>in vitro</em> activity against <em>S. pneumoniae</em>. However, all these drugs are either not available in oral form or have a less favorable safety profile compared to cefpodoxime. When compared with other III generation oral cephalosporins cefixime and ceftibuten, the activity of cefpodoxime against <em>S. pneumoniae</em> was significantly higher based on MIC50/90 values (cefixime – 0.¹²⁵&frasl;₈ mg/l, ceftibuten – 2/≥ 128 mg/l, cefpodoxime – 0.06/4 mg/l) and MICs range (cefixime – 0.06/≥ 128 mg/l, ceftibuten – 0.06/≥ 128 mg/l, cefpodoxime – 0.03/32 mg/l). No strains resistant to β-lactam antibiotics were detected among the tested <em>S. pyogenes</em> isolates. Based on the MIC50/90 values and the range of MIC values, the <em>in vitro</em> activity of cefpodoxime was higher than that of ceftibuten and comparable to that of cefixime.</p> <h3 id="conclusions">Conclusions.</h3> <p>According to the results of our study, as well as in view of its pharmacokinetic profile, high safety and compliance, cefpodoxime can be considered as one of the options for oral therapy of community-acquired bacterial upper and lower respiratory tract infections.</p> http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p350/ Fri, 12 Jan 2024 13:48:46 +0000 http://cmac-journal.ru/en/publication/2023/4/cmac-2023-t25-n4-p350/ <h3 id="objective">Objective.</h3> <p>To analyze the characteristics of patients with severe COVID-19 and lethal outcome.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>This retrospective pharmacoepidemiological study (March – April 2021) enrolled 172 patients with confirmed COVID-19 and death in the intensive care unit of City Clinical Hospital No. 24.</p> <h3 id="results">Results.</h3> <p>The mean age was 74.4 ± 7.4 years, patients over 65 years old – 81% (n = 139), over 75 years old – 44% (n = 75). Males – 66% (n = 113). All patients had a secondary bacterial infection. The predominant COVID-19 complications were respiratory failure (100%), pulmonary edema (96%), multiorgan failure (96%), and acute respiratory distress syndrome (92.4%). All patients had concomitant diseases (cardiovascular – 94.2%, gastrointestinal tract – 81.2%, endocrine – 72.0%). The mean Charlson Comorbidity Index was 7.4 points. The mean length of hospital stay was 12.4 ± 11.0 days (range: 1–36 days), the maximum number of deaths was observed on the 9th day. Analysis of laboratory parameters revealed a significant increase in ferritin, lactate dehydrogenase, and C-reactive protein levels, WBC, absolute lymphocyte count, as well as a decrease in RBC and platelet count at the last measurement before death. All patients received antibiotic therapy (carbapenems – 24%, fluoroquinolones and cephalosporins – 20% each). Antiviral therapy was performed in 62% (n = 106), predominantly with favipiravir (88%).</p> <h3 id="conclusions">Conclusions.</h3> <p>The population of patients with fatal outcome due to COVID-19 was characterized by older age, high Charlson comorbidity index, predominance of cardiovascular, GI tract and endocrine diseases, and high levels of laboratory acute-phase inflammation markers.</p> http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p321/ Fri, 20 Oct 2023 16:25:29 +0000 http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p321/ <h3 id="objective">Objective.</h3> <p>To study the real practice of management of patients with COPD exacerbations on the example of a single hospital.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>During the retrospective descriptive study the data of medical records of 219 patients with COPD were processed, the profile of the studied patients with distribution by phenotypes and determination of the Charlson comorbidity index was compiled and analyzed. StatPlus 7.0 program was used for statistical analysis.</p> <h3 id="results">Results.</h3> <p>According to GOLD guidelines, the majority of patients were in category D (93.2%). Bacteriologic examination of respiratory specimens was done in 127 (57.9%) patients. The microbiological results indicated a high probability of contamination of the majority of samples with oral microflora. Empiric antibacterial therapy was given to 215 (98.2%) patients. In 191 (88.8%) patients, antibiotics were used in monotherapy, and in 24 patients (11.2%) – in combinations. The most frequently used antimicrobials were fluoroquinolones – levofloxacin (34.3%) and ciprofloxacin (43.6%). Cephalosporins of III and IV generations were used much less frequently (2.5 to 7%). There was a weak direct statistically significant association between CRP level and the use of combination antibiotic therapy (V = 0.14, p = 0.047). The purulent sputum had a more pronounced influence on the choice of antibiotic combinations (V = 0.257, p &lt; 0.001). Modification of empirical initial therapy was required in 37 (17.2%) patients.</p> <h3 id="conclusions">Conclusions.</h3> <p>Microbiological results in our study indicate that the majority of respiratory samples were contaminated with oral microflora during the collection of clinical material. The antibiotic therapy prescribed in most cases corresponded to current clinical recommendations, the combined antibiotic therapy was most characteristic of purulent sputum character.</p> http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p304/ Fri, 20 Oct 2023 16:22:09 +0000 http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p304/ <h3 id="objective">Objective.</h3> <p>To describe results of the first experience of using a syndromic approach to the diagnosis of bacteremia using multiplex panels for real-time polymerase chain reaction (real-time PCR).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The prospective study included 10 consecutive positive blood cultures obtained from 10 patients in the intensive care unit after cardiac surgery. Hemocultures were carried out in BacT/ ALERT FA Plus vials using a BacT/ALERT 3D 120 incubator (bioMérieux, France). After short subcultivation on blood agar (4-6 hours), monocultures were identified using a MALDI-ToF mass spectrometer Vitek MS (bioMérieux, France) with sensitivity to antimicrobial drugs determined on a Vitek-2 compact analyzer (bioMérieux, France). The production of carbapenemases was detected phenotypically using a modified carbapenem inactivation method (mCIM test); the molecular type of enzymes was determined using immunochromatographic tests (NG-Test CARBA 5, NG Biotech, France). In parallel with the described process of identifying microorganisms and determining their sensitivity to antibiotics, positive blood cultures were analyzed using a FilmArray 2.0 analyzer and multiplex real-time PCR panels BioFire FilmArray BCID2 (bioMérieux, France).</p> <h3 id="results">Results.</h3> <p>Using MALDI-ToF mass spectrometry, the following microorganisms were identified in the studied blood cultures: <em>K. pneumoniae</em> (n = 5), <em>E. faecalis</em> (n = 2), <em>A. baumannii</em> (n = 1), Raoultella ornithinolytica (n = 1) and <em>S. aureus</em> (n = 1). ⁴&frasl;₅ (80%) of <em>K. pneumoniae</em> isolates were resistant to carbapenems; another 1 isolate produced an ESBL and remained sensitive to carbapenems. All carbapenem-resistant <em>K. pneumoniae</em> gave a positive result of the mCIM test, while the immunochromatographic method detected the production of carbapenemases of the molecular types NDM (n = 1), KPC (n = 1), as well as combinations of KPC + OXA-48 (n = 1) and NDM + OXA-48 (n = 1). All <em>E. faecalis</em> were sensitive to ampicillin, isolates of <em>A. baumannii</em> and R. ornithinolytica remained sensitive to carbapenems, <em>S. aureus</em> was sensitive to cefoxitin. Using the real-time PCR, ⁹&frasl;₁₀ (90%) pathogens were identified to species level in 10 positive blood cultures. In the remaining 1 case (R. ornithinolytica, not included in the list of detected species), the microorganism was assigned to the order <em>Enterobacterales</em>. The data obtained by the traditional method completely coincided with the results of real-time PCR analysis, while the time to obtain results was statistically significantly shorter compared to traditional microbiological method (22 hours versus 49 hours, p &lt; 0.001). In ⁷&frasl;₁₀ (70%) cases, based on the results of real-time PCR analysis, a decision was made to change the tactics of antibiotic therapy.</p> <h3 id="conclusions">Conclusions.</h3> <p>Real-time PCR analysis using BCID2 panels is an effective and reliable tool for the etiological diagnosis of bacteremia.</p> http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p297/ Fri, 20 Oct 2023 16:20:23 +0000 http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p297/ <h3 id="objective">Objective.</h3> <p>Identification of clinical, laboratory, and instrumental factors more common in bacterial pneumonia compared to viral pneumonia, including COVID-19.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>This retrospective case-control study included hospitalized adults with communityacquired bacterial pneumonia and viral lung injury, including COVID-19. Patients were included taking into account age, gender, hospitalization department (general ward or ICU), and Charlson comorbidity index. Clinical, demographic, laboratory, and instrumental data on admission were studied. Unadjusted odds ratios (OR) were calculated using univariate logistic regression (for quantitative indicators) and contingency table analysis (for categorical indicators); adjusted OR were calculated using multivariate logistic regression.</p> <h3 id="results">Results.</h3> <p>The community-acquired bacterial pneumonia group included 100 patients, and the viral lung injury group included 300 patients. Among the causative agents of bacterial pneumonia, <em>Streptococcus pneumoniae</em> was the most common; in the group of viral lung injury, SARS-CoV-2 predominated. In multivariate analysis, the presence of chills (OR and 95% CI: 22.1 [6.8–72.6], p &lt; 0.001), unilateral infiltration according to X-ray or computer tomography (OR and 95% CI: 17.9 [ 7.3–44.1], p &lt; 0.001), altered level of consciousness (OR and 95% CI: 3.2 [1.2–8.5], p = 0.019), use of vasopressors in the first 24 hours of hospitalization ( OR and 95% CI: 11.8 [2.5–55.9], p = 0.002), higher heart rate (OR and 95% CI: 9.1 [2.2–38.6], p = 0.003) and neutrophil/lymphocyte index (OR and 95% CI: 1.4 [1.1–1.9], p = 0.021), as well as the absence of fatigue (OR and 95% CI: 0.2 [0.08–0.40], p &lt; 0.001) and lower total protein (OR and 95% CI: 0.2 [0.02–1.00], p = 0.049) are more typical for bacterial pneumonia compared to viral lung injury.</p> <h3 id="conclusions">Conclusions.</h3> <p>Differential diagnosis between community-acquired bacterial pneumonia and viral lung injury, including COVID-19, requires a comprehensive analysis of clinical, laboratory, and instrumental data.</p> http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p283/ Fri, 20 Oct 2023 16:18:05 +0000 http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p283/ <h3 id="objective">Objective.</h3> <p>To evaluate the results of the implementation of antimicrobial stewardship (AMS) program in a multidisciplinary hospital.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective intervention study was performed in the 600-bed multidisciplinary hospital of the Pirogov National Medical and Surgical Center (Moscow, Russia). The study included a number of sequential interventions, aimed at improving the prevention, diagnosis and treatment of infections, with an assessment of the following indicators dynamics: the structure of microorganisms isolated in the hospital, the level of resistance to antimicrobial drugs (AMD) among the pathogens of the ESKAPE group, the structure of prescribed AMD, as well as an assessment of clinical and economic consequences of antimicrobial resistance changes. For a comprehensive assessment of trend in antibiotic resistance and its connection with consumption of antibiotics, the drug resistance index (DRI) was used. DRI is based on the ratio of the level of resistance of the microorganism and the frequency of administration of AMD, potentially effective against this pathogen. The intervention started in 2013, so the data of 2012 (pre-intervention period) and 2022 were compared in this study.</p> <h3 id="results">Results.</h3> <p>The implementation of AMS program measures helped to reduce the relative frequency of ESKAPE group microorganisms in the structure of nosocomial infection pathogens in the hospital from 36.5% to 22% (p &lt; 0.0001). The proportion of gram-negative (Gr-) isolates resistant to meropenem decreased from 32.4% to 10.9% (p &lt; 0.0001). As a result of the introduction of AMS program, DDDh has been reduced almost three times: from 48.1 to 17.2 DDDh. The median duration of the AMT course in a specialized intensive care unit for the treatment of patients with nosocomial infections decreased from 12 to 8 days (p &lt; 0.0001), the number of AMT days per 1 patient decreased from 7.7 to 4.2 (p &lt; 0.0001). The proportion of ESKAPE pathogens in the structure of bloodstream infections in the hospital decreased from 53.1% to 26% (p &lt; 0.0001), which led to decrease in mortality from 28.4% to 12.8%, (p = 0.012) and length of hospital stay from 31 to 22 days (p &lt; 0.001) in this group of patients.</p> <h3 id="conclusions">Conclusions.</h3> <p>The implementation of AMS program in a multidisciplinary hospital helps to reduce the frequency of inappropriate use of antimicrobial drugs and reduces the consumption of antibiotics, decrease the level of antimicrobial resistance, and in such way improves the results of treatment of patients with nosocomial infections.</p> http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p260/ Fri, 20 Oct 2023 16:11:05 +0000 http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p260/ <h3 id="objective">Objective.</h3> <p>To assess biapenem PK parameters in critically ill adult patients and define the optimal dosing regimens based on TDM data.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>An open, prospective, uncontrolled, single-center study based on City Clinical Hospital No. 24, Moscow (October 2022 – April 2023), included patients over 18 years of age with a diagnosed severe bacterial infection received 600 mg of biapenem as 3-hour intravenous infusion every 12 hours in the intensive care unit. Blood sampling during the TDM included taking blood samples immediately before the next infusion of biapenem to determine the residual concentration (Ctrough) and immediately after the end of the infusion to determine the peak concentration (Cmax). Concentrations were assessed using HPLC-UV method.</p> <h3 id="results">Results.</h3> <p>Total population – 20 patients (75% ≥ 60 years; 65% women). The main indications for biapenem were lower respiratory tract infections (80%) and intra-abdominal infections (35%). Bacterial culture tests revealed growth in 45% (<em>Klebsiella pneumoniae</em> – 87,5%). During the TDM 40 samples were obtained (Cmax from 15 to 42 mg/l (mean – 28.7 mg/l), Ctrough from 0.5 to 15 mg/l (mean – 3.56 mg/l)). The Kel value ranged from 0.09 to 0.48 1/h (mean – 0.29 1/h); Vd – from 7.41 to 42.49 l (mean – 16.33 l); T1/2 – from 1.4 to 7.5 hours (mean 2.94 hours). Probability of target attainment (%fT ≥ MIC) was assessed depending on MIC. For MIC of 2 mg/l, 40%fT ≥ MIC was achieved in 100%, 60%fT ≥ MIC – in 100%; 80%fT ≥ MIC – in 75%. For MIC – 8 mg/l, 40%fT ≥ MIC was achieved in 90%, 60%fT ≥ MIC – in 45%, 80%fT ≥ MIC – in 15%.</p> <h3 id="conclusions">Conclusions.</h3> <p>The dosing regimen 600 mg of biapenem as 3-hour intravenous infusion every 12 hours demonstrated achievement of effective antibiotic concentrations in blood plasma of critically ill patients exceeding the MIC (2 mg/l). To manage patients infected with resistant strains (MIC of 4–16 mg/l) it is necessary to perform additional studies assessing PK parameters of biapenem at higher doses.</p> http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p247/ Fri, 20 Oct 2023 16:08:32 +0000 http://cmac-journal.ru/en/publication/2023/3/cmac-2023-t25-n3-p247/ <h3 id="objective">Objective.</h3> <p>To assess the practice of using antibiotics (AB) by the population of various regions of the Russian Federation (RF), by studying attitudes, behavior and knowledge about AB.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The survey was conducted from February to June 2022 as part of a multicenter qualitative study in the form of a semi-structured interview among respondents from 18 to 74 years old who used systemic ABs of any group with or without a doctor&rsquo;s prescription for the treatment of symptoms of a confirmed or probable infectious disease for 3 months prior to the study. Individual inclusion criteria or respondents were developed for each of the participating centers (8 Federal Districts (FD) of the RF, Moscow, St. Petersburg), considering gender, age, education and place of residence to ensure the representativeness of the sample of the general population.</p> <h3 id="results">Results.</h3> <p>The study interviewed 300 respondents. Among them are 151 interviews with respondents who have a prescription for AB. A variety of reasons were identified for which the respondents did not go to the doctor: lack of time, fear of contact with additional infections in health facilities, positive experience with the use of a particular AB, confidence in the free purchase of AB in a pharmacy without a prescription. The data obtained testify to the high level of confidence of the interviewees in the experience and advice of others in the matter of starting AB therapy. A large role in the spread of resistance to AB belongs to the non-compliance of pharmacy workers with the requirements for the prescription sale of AB. As a rule, the respondents had no difficulty in purchasing AB without a doctor&rsquo;s prescription. Among ABs, combinations of penicillins with beta-lactamase inhibitors, penicillins, and macrolides were in greatest demand. An insufficient level of knowledge about the mechanism of action and indications for the use of AB was revealed. Data were obtained on the insufficient percentage of coverage of the population with information campaigns on the rational use of AB. A significant impact of the COVID-19 pandemic on an increase in the incidence of AB self-treatment has been demonstrated.</p> <h3 id="conclusions">Conclusions.</h3> <p>The problem of excessive and irrational use of AB among the population in the RF still exists despite the ongoing measures. A lack of knowledge about antibiotics and low awareness of the problem of antimicrobial resistance were identified, and factors contributing to self-medication were identified. The data obtained can serve as a basis for the development of future initiatives to ensure the proper use of AB and, therefore, help to reduce the rate of selection of resistant microorganisms in the regions of the RF.</p> http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p211/ Sun, 16 Jul 2023 16:10:50 +0000 http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p211/ <h3 id="objective">Objective.</h3> <p>Analysis of the distribution of the values of the minimum inhibitory concentrations (MIC) of a number of antibacterial drugs in relation to representatives of the order Flavobacteriales isolated from respiratory samples from patients with cystic fibrosis of the Russian Federation by the method of double serial dilutions.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The distribution of the values of MIC of a number of antibacterial drugs was evaluated in relation to 100 strains of bacteria, representatives of the order Flavobacteriales, isolated from respiratory samples from patients with cystic fibrosis from 60 regions of the Russian Federation as part of a routine microbiological examination. Of these, 75 representatives of Chryseobacterium spp., among which C. arthrospherae – 28, C. formosense – 1, C. gambrini – 3, C. gleum – 10, C. indologenes – 20, C. joostei – 1, C. oraniemense – 10, C. shandongense – 2 strains, 4 strains of Elizabethkingia spp., among which 2 – E. miricola, and one strain of E. meningoseptica and E. anopheles, respectively, as well as 21 strains of E. falsenii. Identification of all isolated cultures was carried out using MALDI-ToF mass spectrometry (Bruker, Germany). The MIC values were determined for 17 antimicrobial drugs: amikacin, amoxicillin/clavulanate, aztreonam, cefotaxime, ceftazidime, ceftazidime/avibactam, ceftolozane/ tazobactam, ciprofloxacin, colistin, ertapenem, gentamicin, imipenem, meropenem, piperacillin/ tazobactam, tigecycline, tobramycin and trimethoprim/sulfamethoxazole using Sensititre kits DKMGN.</p> <h3 id="results">Results.</h3> <p>The MIC values of colistin, cefotaxime and tobramycin more than 8 µg/ml, as well as more than 2 µg/ml with respect to ertapenem was demonstrated for 100% of isolates. For most strains, the MIC values of imipenem and meropenem were more than 4 µg/ml. MIC of ceftazidime against 20% of Chryseobacterium spp. strains was up to 2 µg/ml. Indicators of MIC of amikacin in relation to Elizabethkingia spp. strains were 32 µg/ml or more. For 38% of the strains of Chryseobacterium spp. and E.falsenii, this value did not exceed 8 µg/ml. As in the case of amikacin, all Elizabethkingia spp. strains demonstrated high levels of gentamicin MIC – 8 µg/ml (25% of strains) and more (75% of strains). For 20% of all tested strains, the MIC value was in the range of ≤ 2 µg/ml. In relation to half of the tested isolates, the MIC values for ceftazidime/avibactam, as well as ceftolozane/tazobactam were at the level of up to ²&frasl;₄ µg/ml inclusive. More than a third of the strains had a level of MIC ciprofloxacin up to 0.25 µg/ml inclusive. For 25% of strains, the level of MIC of tigecycline was up to 0.5 µg/ml, inclusive, the lowest MIC indicators for the tested group of strains were demonstrated for trimethoprim/sulfamethoxazole: for 88% of strains, the MIC value was ≤ ¹&frasl;₁₉ µg/ml, for another 9% of strains, this indicator was ²&frasl;₃₈ µg/ml.</p> <h3 id="conclusions">Conclusions.</h3> <p>Representatives of the order Flavobacteriales are a group of microorganisms characterized by multiple antibiotic resistance. Most strains isolated from patients with cystic fibrosis in the Russian Federation retain low MIC values for trimethoprim/sulfamethoxazole.</p> http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p202/ Sun, 16 Jul 2023 16:06:36 +0000 http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p202/ <h3 id="objective">Objective.</h3> <p>To evaluate frequency of pharyngeal and rectal mucosa colonization by <em>K. pneumoniae</em> strains in infants with congenital heart defects at the stage of cardiosurgical hospital admission, as well as dynamic analysis of production frequency and molecular structure of <em>K. pneumoniae</em> carbapenemases.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 1445 patients with risk factors (antibiotic therapy in the anamnesis, emergency hospitalization, transfer from other hospitals) admitted for surgical treatment of congenital heart defects (CHDs) between January 1, 2020 and December 31, 2022 were included in the retrospective analysis. Median age was 1.08 months (between 0 and 12 months). Smears from the pharyngeal and rectal mucosa (2890 samples) were taken for microbiological examination no later than 72 h after admission. The isolation of extended-spectrum beta-lactamases (ESBLs) and/or carbapenemases producing <em>K. pneumoniae</em> in the absence of symptomatic infection was considered as colonization. <em>K. pneumoniae</em> strains were considered as &laquo;problematic&raquo; in the absence of susceptibility to three or more groups of antimicrobials: the third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides. The profile of antibiotic resistance, carbapenemases production and their molecular type were determined in the isolated strains.</p> <h3 id="results">Results.</h3> <p><em>K. pneumoniae</em> carriage with &laquo;problematic&raquo; sensitivity was detected in 252 out of 1445 (17.4%) patients: 153 out of 1445 (10.6%) children were colonized by only ESBLs producers, and 99 out of 1445 (6.9%) children – by both ESBLs and carbapenemases producers. In dynamics, the number of ESBLs producers carriers decreased by 1.5 times (50 out of 448 – 11.2% and 37 out of 506 – 7.3% in 2020 and 2022, respectively). The number of <em>K. pneumoniae</em> producing both ESBLs and carbapenemases carriers increased by 4.9 times (11 out of 448 – 2.5% and 62 out og\f 506 – 12.3% in 2020 and 2022, respectively), in 2022 exceeding the proportion of only ESBLs producers carriers by 1.7 times. The molecular structure of carbapenemases was represented by OXA-48 carbapenemases (44 out of 99 – 44.5%), NDM metalloenzymes (35 out of 99 – 35.4%), OXA-48 and NDM combinations (13 out of 99 – 13.1%), KPC (3 out of 99 – 3%), NDM, KPC and OXA-48, NDM and KPC combinations: 3 out of 99 – 3% and 1 out of 99 – 1% of carriers, respectively. In dynamics, the number of isolates with the production of OXA-48 carbapenemases increased by 34.8% (from 18.2% to 53% in 2020 and 2022, respectively), NDM carbapenemases and co-producers of OXA-48, NDM decreased by 25.9% (from 54.5% to 28.6% in 2020 and 2022) and 19.1% (from 27.3% to 8.2% in 2020 and in 2022), respectively. In 2022, strains with the production of KPC carbapenemases and co-producers of carbapenemases of three classes (OXA-48, NDM and KPC) were identified for the first time.</p> <h3 id="conclusions">Conclusions.</h3> <p>The data obtained indicate an increase in the frequency of initial colonization of patients with carbapenem-resistant <em>K. pneumoniae</em>, an expansion of the structure of carbapenemases produced by them, that, if infection control measures are not followed, can increase the frequency of infections caused by them.</p> http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p179/ Sun, 16 Jul 2023 16:01:51 +0000 http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p179/ <h3 id="objective">Objective.</h3> <p>To analyse aggregated AST results for key microorganisms collected through the 2022 reports of chief specialists in clinical microbiology and antimicrobial resistance.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included an analysis of the interpretation criteria used in the laboratories and an evaluation of the AST reports. Data were obtained from the clinical microbiology and antimicrobial resistance annual reporting system. Reports were analyzed using EUCAST guidelines for expected resistance phenotypes and expected susceptible phenotypes. Data processing and analysis were realized using the «R» programming language. The 95% CI for the percentages of inaccuracies/errors distributed by federal districts was calculated using the Wilson method.</p> <h3 id="results">Results.</h3> <p>A combination of several interpretation standards was used in 27.78% of laboratories, MUK 4.2.1890-04 was noted as one of the options in 57.6% of laboratories. Irrelevant standards of interpretation with a lag of 1 year or more were used in a significant number of cases. The highest percentage of errors/ inaccuracies by the type «expected resistance» was observed for <em>A. baumannii</em> – 14,06% (N = 9163), <em>E. faecium</em> – 8,05% (N = 3451) and <em>S. pneumoniae</em> – 6,18% (N = 2779). «Susceptibility categorization in the absence of interpretive breakpoints» was highest for <em>S. aureus</em> – 13.24% (N = 19784) and <em>S. pneumoniae</em> – 8.76% (N = 3942). Rare phenotype was determined in the highest percentage in relation to <em>S. pneumoniae</em> and antimicrobials: vancomycin – 54.04% and linezolid – 64.6%.</p> <h3 id="conclusions">Conclusions.</h3> <p>The study revealed a significant number of errors/inaccuracies in the data reported. The use of irrelevant interpretation criteria, the exclusion of situations with rare phenotypes and expected resistance, may contribute to a significant increase in the likelihood of inappropriate antibacterial prescribing.</p> http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p159/ Sun, 16 Jul 2023 15:55:34 +0000 http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p159/ <h3 id="objective">Objective.</h3> <p>To analyze spontaneous reports (SRs) from the Russian database of adverse reactions (Automated information system &laquo;Pharmacovigilance&raquo; of Roszdravnadzor), containing information on fatal outcomes during ceftriaxone treatment, and to identify factors associated with an increased risk of death with ceftriaxone use.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study included 122 SRs concerning fatal cases during ceftriaxone therapy. All SRs were submitted to the Russian pharmacovigilance database from 06 May 2019 to 23 November 2022. A retrospective analysis of fatal adverse reactions cases in ceftriaxone treatment was carried out according to the following parameters: gender, age, drug intake and route of administration, clinical symptoms of anaphylaxis. Additionally, indications for the simultaneous use of drugs for local anesthesia as a solvent were evaluated.</p> <h3 id="results">Results.</h3> <p>A total of 86 SRs (70.5%) were primary and relevant for further analysis. 16 SRs (18.6%) were registered in the database for 8 months of 2019, 25 (29.1%) – for 2020, 15 (17.4%) – for 2021, for less than 11 months 2022 received 30 reports (34.9%). The number of adverse reactions reports in male and female patients was similar. Among the age groups, the largest number of SRs was observed in middleaged and elderly patients – 27 (31.4%) and 23 (26.7%) reports, respectively, 8 cases (9.3%) were registered in pediatric population. The development of fatal adverse reactions in the hospital was reported in 50 (58.1%) SRs, in outpatient setting – in 31 (36.1%) SRs. 18 SRs were identified with an indication of the patient’s self-treatment, which is 20.9% of all primary reports. Clinical symptoms of anaphylactic shock were noted in 63 reports (73.3%). Additional analysis of the combined use of ceftriaxone and local anesthetics cases revealed a range of medical errors.</p> <h3 id="conclusions">Conclusions.</h3> <p>Ceftriaxone treatment was associated with a high risk of anaphylactic shock. The use of this antibiotic in outpatient setting, especially as self-treatment is an additional risk factor for death. Inappropriate use of local anesthetics in combination with ceftriaxone is an additional serious risk factor for fatal outcome.</p> http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p150/ Sun, 16 Jul 2023 15:52:19 +0000 http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p150/ <h3 id="objective">Objective.</h3> <p>To evaluate prescribing patterns of antimicrobials and quantify them in relation to quality indicators in Russian multi-field hospitals.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Point Prevalence Survey of Antimicrobial Consumption as a part of an international Global-PPS project was conducted in 8 multi-field hospitals in different Russian cities (Krasnoyarsk, Moscow, Omsk, Saratov, Smolensk, Ulan-Ude, Yakutsk) during the period from May till December 2021. Case records of patients who received therapeutic or prophylactic systemic antimicrobial agents were analyzed. Local practices of antimicrobials’ utilization were evaluated in relation to quality indicators defined by the study protocol.</p> <h3 id="results">Results.</h3> <p>Common mistakes requiring a prompt intervention included low adherence to clinical guidelines, absence of stop/review dates in the medical records, extended duration of surgical prophylaxis, III generation cephalosporin’s overuse and low rate of targeted therapy.</p> <h3 id="conclusions">Conclusions.</h3> <p>The results of the project can be valuable for the improvement to antimicrobial utilization approaches at the study centers as well as for monitoring of antimicrobial stewardship programs’ implementation.</p> http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p142/ Sun, 16 Jul 2023 15:50:19 +0000 http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p142/ <h3 id="objective">Objective.</h3> <p>To compare efficacy and safety of 14-day triple eradication therapy with the addition of methylmethionine sulfonium chloride and a probiotic complex and 14-day triple eradication therapy boosted with bismuth tripotassium dicitrate and a probiotic complex in a prospective comparative randomized clinical trial.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 70 patients with confirmed <em>H. pylori</em> infection were enrolled into the study. The first group (n = 35) received esomeprazole 20 mg 2 bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid for 14 days, methylmethionine sulfonium chloride 300 mg once a day for 1 month, probiotic complex (bifidobacteria [Bifidobacterium longum CBT BG7, Bifidobacterium lactis CBT BL3, Bifidobacterium bifidum CBT BF3], lactobacilli [Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5], Streptococcus thermophilus CBT ST3) 1 capsule once a day for 1 month. The second group (n = 35) received esomeprazole 20 mg 2 bid, clarithromycin 500 mg 2 bid, amoxicillin 1000 mg 2 bid and bismuth tripotassium dicitrate 240 mg 2 bid for 14 days, probiotic complex (bifidobacteria [Bifidobacterium longum CBT BG7, Bifidobacterium lactis CBT BL3, Bifidobacterium bifidum CBT BF3], lactobacilli [Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5], Streptococcus thermophilus CBT ST3) 1 capsule once a day for 1 month. Eradication of <em>H. pylori</em> was assessed using stool antigen test.</p> <h3 id="results">Results.</h3> <p>Eradication rates for the first and second groups in the intent-to-treat (ITT) population were 77.1% and 88.6% (p = 0.205), respectively. In the per-protocol (PP) population, eradication rates were 81.8% and 96.9% (p = 0.051), respectively. Adverse events were reported in 34.3% of patients in the first group and 34.3% of patients in the second group (p = 1).</p> <h3 id="conclusions">Conclusions.</h3> <p>14-day standard triple therapy boosted with bismuth tripotassium dicitrate and a probiotic complex demonstrates high efficacy and safety profile, and therefore can be recommended as first-line therapy for <em>H. pylori</em> infection in adults.</p> http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p116/ Sun, 16 Jul 2023 15:43:39 +0000 http://cmac-journal.ru/en/publication/2023/2/cmac-2023-t25-n2-p116/ <h3 id="objective">Objective.</h3> <p>To characterize the genomes of oxacillin-susceptible mecA-positive <em>Staphylococcus aureus</em> ST59 isolated in St. Petersburg.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Nine oxacillin-susceptible mecA-positive of <em>S. aureus</em> isolates (OS-MRSA) of ST59 were included in the study. The isolates were obtained from children who showed no clinical signs of staphylococcal infections during nasal screening of <em>S. aureus</em> in St. Petersburg in 2018–2019. One isolate was obtained from an adult patient with skin and soft tissue infection (SSTI). The susceptibility to antibiotics and whole genome sequencing were performed. The analysis included 242 genomes of <em>S. aureus</em> ST59 from open access databases.</p> <h3 id="results">Results.</h3> <p>By employing the broth serial dilution and VITEK, the isolates&rsquo; phenotypic susceptibility to oxacillin was determined. The cefoxitin inhibition zones ranged from 17 to 22 mm. All isolates showed a penicillinclavulanate MIC ≤ 0.5 µg/mL. Isolates obtained from carriers belonged to the ST59-t1950-SCCmec Vb (seb+) genotype whereas the isolate obtained from SSTI belonged to the ST59-t437-SCCmec Vb (seb/ lukF/lukS+) genotype. Nucleotide position -33 (C/T) of mecA promoter and mutations in PBP2a (S225R + E246G) were present in all isolates. Based on phylogenetic analysis and Bayesian clustering the ST59 genomes were divided into four clusters and all Russian genomes belonged to the East Asian ST59 sublineage. The PVL toxin was present in the genomes of the first cluster of the East Asian ST59 sublineage. Pairwise comparisons of nucleotide substitutions among the genomes of Russian isolates showed a high similarity: median 13, interquartile range 8–18. All ST59 clusters were characterized by the presence of enterotoxin B, as well as mutations in PBP2a (S225R and E246G) and the promoter regions of the mecA gene (-7 G/A or -33 C/T). The genomes of the Russian isolates differed from the globally spread ST59 by specific mutations at the following loci (relative to the reference genome of <em>S. aureus</em> M013TW): lactose catabolism regulator RS03495 (N168D), ribosomal protein L28 (V47A), putative glyoxalase RS07825 (V42A), and the hypothetical protein RS13235 (K32E).</p> <h3 id="conclusions">Conclusions.</h3> <p>Russian MRSA-ST59 isolates belong to the East Asian sublineage and are characterized by the presence of the enterotoxin B gene. Oxacillin susceptibility and borderline resistance to cefoxitin are specific characteristics of MRSA-ST59. OS-MRSA phenotypes have a risk of improper sensitivity testing leading to ineffective antibiotic treatment. Detection of mecA gene is the most accurate method for differentiating between MSSA and MRSA.</p> http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p93/ Sun, 19 Mar 2023 10:39:14 +0000 http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p93/ <h3 id="objective">Objective.</h3> <p>To identify risk factors for fatal outcome and COVID-19-associated liver damage in hospitalized adult patients with coronavirus infection.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>In a retrospective cohort study, 389 cases of patients with coronavirus infection complicated by bilateral viral pneumonia were studied. Demographic characteristics, clinical features of the course of the disease, anamnestic data, results of laboratory and instrumental methods of examination were analyzed and correlated with mortality. At the time of admission, the following were taken into account: fever, severity of the patient&rsquo;s condition according to COVID-19 classification of severity, body mass index (BMI), oxygen saturation (SpO2), percentage of lung tissue damage according to computed tomography (CT). Laboratory indices of biochemical blood analysis were assessed in dynamics: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, total protein, albumin, C-reactive protein (CRP). Data analysis was performed using the R programming language (ver. 4.1.1.).</p> <h3 id="results">Results.</h3> <p>The following risk factors, assessed at the time of hospitalization, increased the likelihood of death: severe and extremely severe condition of the patient (RR = 4.77; 95% CI: 3.33–6.83); SpO2 less than 93% (RR = 3.76; 95% CI: 2.57–5.49); diabetes mellitus (RR = 2.94; 95% CI: 2.01–4.30); lung tissue damage CT-3 and CT-4 (RR = 2.66; 95% CI: 1.79–3.75); concomitant chronic pyelonephritis and chronic kidney disease (CKD) (RR = 2.59; 95% CI: 1.79–3.74); age 65 years and older (RR = 2.50; 95% CI: 1.70–3.67); ischemic heart disease (IHD) (RR = 2.39; 95% CI: 1.42–4.01); an increase in the level of CRP more than 15 mg/l (RR = 2.22; 95% CI: 1.16–4.24); BMI 35 kg/m2 or more (RR = 1.89; 95% CI: 1.28–2.77); AST level more than 2 upper limit of normal (ULN) (RR = 1.75; 95% CI: 1.20–2.55). Risk factors for an increase in AST more than 2 ULN were: SpO2 less than 93% (RR = 1.53; 95% CI: 1.15– 2.03), severe and extremely severe course of coronavirus infection (RR = 1.83; 95% CI: 1.38–2.43), concomitant chronic liver disease (RR = 1.45, 95% CI: 1.08–1.95).</p> <h3 id="conclusions">Conclusions.</h3> <p>Risk factors for fatal COVID-19 in hospitalized patients are: severe and extremely severe initial condition of the patient, oxygen saturation less than 93%, lung tissue damage more than 50%, age older than 65 years, presence of concomitant diabetes mellitus, chronic pyelonephritis and CHD, CHD, obesity, increased CRP level more than 15 mg/l, and AST more than 70 units/l. Elevation of AST over 2 IU/L can be considered as one of the prognostic laboratory markers of adverse prognosis COVID-19.</p> http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p84/ Sun, 19 Mar 2023 10:31:58 +0000 http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p84/ <h3 id="objective">Objective.</h3> <p>To evaluate the existing patterns of antimicrobials dispensing in community pharmacies during the COVID-19 pandemic.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>In a cross-sectional study conducted from October 2020 to January 2021 it was obtained the data on the major antimicrobials dispensing in community pharmacies in Moscow and four regions of Russian Federation: date of release, customer’s age and gender, drug name and formulation, the reason for the release (symptoms, preliminary or confirmed diagnosis), prescription-based supply or not/emergency releasing.</p> <h3 id="results">Results.</h3> <p>The study included 71 pharmacies, including 41 private and 30 public organizations. During the mentioned period of time 5514 antimicrobials were supplied to 5270 customers. Antibiotics and antiviral drugs for systemic use accounted the largest share in the structure of purchased antimicrobials (60.5% and 26.3% of all sales, respectively). The frequency of non-prescription-based supplies was 28.5%. The greatest demand among antibiotics was registered for macrolides (14.9%), combinations of penicillins with beta-lactamase inhibitors (12.3%) and fluoroquinolones (11.4%). Upper respiratory tract infections were the most frequent reason for antimicrobials releasing – 36,9%. COVID-19 was the reason for 8.4% of antimicrobials sales. Azithromycin and umifenovir were the most frequently used drugs for SARS-CoV-2.</p> <h3 id="conclusions">Conclusions.</h3> <p>Antibiotics for systemic use have still remained the commonly used ones, whereas upper respiratory tract infections are the main indication for their purchase. Nearly a third of antimicrobials, including systemic antibiotics, were dispensed in private pharmacies without prescription. COVID-19 is uncommon cause of outpatient antimicrobial sales, but a common reason for systemic antibiotic prescribing.</p> http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p77/ Sun, 19 Mar 2023 10:29:48 +0000 http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p77/ <h3 id="objective">Objective.</h3> <p>To study the antibacterial activity of lysostaphin against staphylococci various species, as well as its effect on the viability of Vero cells.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Lysostaphin was obtained by genetic engineering. Purification of the protein was carried out on SP-sepharose, the purity was determined by electrophoresis in PAGE by Lamley. The susceptibility to lysostaphin of 9 species 175 strains of staphylococci was studied. Identification was performed by MALDI-TOF MS, antibiotic susceptibility by EUCAST (v. 11.0). The MIC of lysostaphin was studied by the method of serial dilutions with concentrations between 0.015 and 512 mg/l. For 72 hours, the viability of Vero cells with lysostaphin at concentrations of 0.5-32.0 mg/l was determined by the MTT method with counting of living cells according to their growth curve. The results were analyzed by ANOVA followed by Dunnett&rsquo;s test.</p> <h3 id="results">Results.</h3> <p>A kinetic study of <em>S. aureus</em> growth in the presence of revealed an inhibitory effect of endopeptidase (MIC 0.06 mg/l). Lysostaphin was characterized by pronounced activity against clinical methicillinsensitive <em>S. aureus</em>. The MIC ranged between 0.03 and 0.5 mg/l and the MIC50/90 was 0.¹²⁵&frasl;₀.5 mg/l. For methicillin-resistant <em>S. aureus</em> MIC50/90 0.²⁵&frasl;₀.5 mg/l. The MIC50 for MRSE was 2 times higher than for MSSE – 1 mg/l. The maximum MIC value was determined against isolates of S. warneri and <em>S. hominis</em> – 64 mg/l, the lowest for S. saprophyticus – 0.5 mg/l. MIC50 of lysostaphin against MRSA was 4 times lower than that of vancomycin, MIC90 was 3 times lower. Differences in viable cells depending on the concentration of lysostaphin were not found.</p> <h3 id="conclusions">Conclusions.</h3> <p>Significant activity of lysostaphin against staphylococci was revealed, which is several times higher than vancomycin against MRSA. Lysostaphin was also effective against methicillin-resistant <em>S. aureus</em>. The high anti-staphylococcal activity and cytocompatibility of lysostaphin are promising for its further study in the prevention and treatment of staphylococcal orthopedic infections.</p> http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p68/ Sun, 19 Mar 2023 10:27:33 +0000 http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p68/ <h3 id="objective">Objective.</h3> <p>To review the key principles and functionality of AMRexpert online platform.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The information part of the platform is comprised of rules based on the EUCAST recommendations and various standards for interpreting the results of antimicrobial susceptibility testing (EUCAST, CLSI versions 2020-2022). The technical part of the platform was developed using C# programming language, Angular and Bootstrap frameworks. AST results of <em>Serratia marcescens</em>, <em>Pseudomonas aeruginosa</em>, <em>Staphylococcus saprophyticus</em>, <em>Enterococcus faecium</em> specific isolates were analyzed for practical testing of the platform using EUCAST v.12.0, 2022 interpretation criteria.</p> <h3 id="results">Results.</h3> <p>The developed platform for the evaluation of microbiological reports includes a wide list of expert rules, various standards for the interpretation of the AST results. Consistent data input, the ability to switch forms between several microorganisms, and the presentation of evaluation results in the form of blocks allows all necessary information to be structured. Practical use of the platform is available for various infectious pathogens. Fast and efficient interaction between users is provided by different options for sharing and saving the results.</p> <h3 id="conclusions">Conclusions.</h3> <p>The web-based application evaluates microbiological reports in a comprehensive approach, with the ability to apply the results later to prescribe antimicrobial therapy. The platform for the interpretation, verification and validation of the AST results – AMRexpert can be accessed at <a href="https://amrexpert.ru" target="_blank">https://amrexpert.ru</a>.</p> http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p34/ Sun, 19 Mar 2023 10:15:37 +0000 http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p34/ <h3 id="objective">Objective.</h3> <p>To perform pharmacoepidemiological analysis of spontaneous reports of adverse drug reactions (ADRs) occurred during macrolide group antibiotics prescription and registered in the “Pharmacovigilance 2.0” subsystem of the Federal Service for Surveillance in Healthcare.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective pharmacoepidemiological analysis of spontaneous reports of ADRs arising from the use of all macrolide and azalide antibiotics registered in Russia and registered in the electronic database of the “Pharmacovigilance 2.0” subsystem of the Federal Service for Surveillance in Healthcare for the period from 01.04.2019 to 30.11.2022 was performed.</p> <h3 id="results">Results.</h3> <p>Analysis of the number of spontaneous reports of ADRs, their structure, outcomes and severity criteria was performed. The most clinically significant ADRs were identified, the occurrence of which was reported to pharmacovigilance bodies. The results of a retrospective pharmacoepidemiological analysis showed that the development of complications of pharmacotherapy in most cases was associated with the use of azithromycin and clarithromycin. The main clinical manifestations of adverse drug reactions were skin and subcutaneous tissue disorders, gastrointestinal disorders, as well as general disorders and injection site reactions.</p> <h3 id="conclusions">Conclusions.</h3> <p>It was found that the reported events generally corresponded to the general spectrum of ADRs typical for individual representatives of macrolide and azalide antibiotics.</p> http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p26/ Sun, 19 Mar 2023 10:01:37 +0000 http://cmac-journal.ru/en/publication/2023/1/cmac-2023-t25-n1-p26/ <h3 id="objective">Objective.</h3> <p>The purpose of this study is to systematize and comprehensively evaluate safety data on the drug favipiravir using the national pharmacovigilance database of the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The report is based on spontaneous reports in the national automated information system of pharmacovigilance of the Russian Federation for the reporting period from 01.01.2020 – 04.07.2022. To identify safety signals we used disproportionality analysis, to estimate consumption of favipiravir – indicator of the number of consumed DDDs, we additionally performed review of concomitant therapy as a risk factor for serious adverse reactions.</p> <h3 id="results">Results.</h3> <p>A total of 412 reports of 585 adverse reactions was included in the analytic phase. The largest number of reports referred to liver and biliary tract disorders – 166 (38%), gastrointestinal disorders – 93 (16%), changes in laboratory and instrumental data – 53 (9%), and immune system disorders – 44 (7%). A total consumption of oral favipiravir expressed in the number of maintenance daily doses for 2021 was 46,417,274.87, i.e. 30 times the consumption of remdesivir and 6 times the consumption of hydroxychloroquine. One potential statistical safety signal such as hypercreatininemia was identified.</p> <h3 id="conclusions">Conclusions.</h3> <p>Development of hypercreatininemia is a potential statistical safety signal of favipiravir, which requires further validation.</p> http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p395/ Fri, 20 Jan 2023 10:41:35 +0000 http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p395/ <p>Photodynamic inactivation (PDI) is an alternative to antibiotic therapy method for biocidal action against microorganisms, which can be used for lithotripsy and sanitation of the bladder cavities.</p> <h3 id="objective">Objective.</h3> <p>Selection of parameters and application PDI against uropathogenic microorganisms.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>In this study we used bacterial strains isolated from urine samples of patients. Differentiation media and biochemical plates were used for identification of microorganisms. The sensitivity of uropathogenic microorganisms to PDI was studied on pure cultures and in native urine. The photosensitizer “Photoditazine” (50 µg/ml) was used in the work, as well as Triton X-100 (5 % vol.) was applying to increase the permeability of the cell wall of gram-negative microorganisms. The samples were irradiated by a medical laser device “Latus-K” with a wavelength of 662 nm. To assess the effectiveness of PDI, the values of the logarithmic decrease of colony-forming unit (CFU) of the microorganisms were calculated. Statistical analysis was made by Statistica 10.0 and Mann-Whitney criterion.</p> <h3 id="results">Results.</h3> <p>50 strains of uropathogens belonging to 18 species were isolated from 36 samples of native urine. Among them, the most common were <em>S. aureus</em>, <em>E. coli</em>, <em>P. aeruginosa</em>, <em>K. pneumoniae</em>. The value of logarithmic decrease in CFU for gram-positive bacteria ranged from 5 to 6, which corresponds to inactivation 99.999-99.9999% of bacterial cells in a sample. For gram-negative strains, this value was slightly lower and ranged from 4 to 5.5, which, nevertheless, corresponds to inactivation 99.99-99.999% of CFU bacteria. The addition of Triton X-100 increase the efficiency from 46% to 99.99% for <em>E. coli</em>, from 99% to 99.99% for <em>P. mirabilis</em>, from 16% to 94% for <em>K. pneumoniae</em> and from 97% to 99.999% for <em>P. aeruginosa</em>. It should be noted that the PDI was affect microorganisms both in isolated pure cultures and in native urine.</p> <h3 id="conclusions">Conclusions.</h3> <p>Photodynamic inactivation may be considered as an alternative to antibiotic therapy method of biocidal action against uropathogenic microorganisms.</p> http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p388/ Fri, 20 Jan 2023 10:39:28 +0000 http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p388/ <h3 id="objective">Objective.</h3> <p>To analyze new strategies for the treatment of community-acquired pneumonia (CAP) by age and assess treatment efficacy by age category based on real world data.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 612 patients (medical charts) with CAP treated in 3 hospitals during the 2017–2019 were included in the retrospective pharmacoepidemiological study. A retrospective analysis of antimicrobial therapy (AMT) administration in the treatment of CAP was performed.</p> <h3 id="results">Results.</h3> <p>Duration of hospital stay in CAP patients of young age was 10% shorter than in patients of any other age category. The least frequency (19.6%) of antibiotic combination administration as initial empiric therapy was found in patients of young age. There were no significant differences in frequency of initial AMT administration between age groups. Ceftriaxone, cefepime and cefoperazone were the most common antimicrobials used as monotherapy in all age groups. Ceftriaxone with azithromycin combination was the most common (42%) initial combination therapy in all age groups. The highest number (27) of various antibiotic combinations was administered to old patients, and the lowest number (16) – to young patients. Efficacy of initial AMT was similar between elderly and old patients. Overall efficacy of initial AMT in patients with non-severe CAP and severe CAP was 54% and 50%, respectively. Analysis of antimicrobial treatment of CAP in real practice and its compliance with the current clinical guidelines showed cephalosporin plus macrolide to be a predominant antibiotic combination (83%).</p> <h3 id="conclusions">Conclusions.</h3> <p>Antibiotic combination administration was found to be common in patients with non-severe CAP, whereas initial monotherapy was administered to severe CAP patients. Antibiotic prescription pattern in patient of young age was different from that in any other age groups. CAP had a less severe course in young patients as evidenced by shorter duration of hospital stay, more frequent monotherapy administration and higher efficacy of initial AMT compared to other age categories. There were no prescriptions of the recommended fifth generation cephalosporin (ceftaroline fosamil).</p> http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p383/ Fri, 20 Jan 2023 10:36:59 +0000 http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p383/ <h3 id="objective">Objective.</h3> <p>To compare the efficacy of ceftazidime-avibactam and aztreonam combination therapy with “standard” therapy in patients with hematological malignancies and sepsis, caused by carbapenemresistant <em>K. pneumoniae</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>In this open, single center prospective-retrospective, cohort study, during 2019–2022, we analyze medical documentation of 81 hospitalized patients with hematologic malignancies and <em>K. pneumoniae</em> sepsis. <em>K. pneumoniae</em> was identified by MALDI-TOF mass-spectrometry; antimicrobial susceptibility testing was performed in accordance with current versions of EUCAST guidelines. Patients with sepsis, caused by carbapenem-resistant <em>K. pneumoniae</em> isolates (n = 53), received either ceftazidimeavibactam plus aztreonam combined therapy (1st group, n = 26), or “standard” antimicrobial therapy (2nd group, n = 27).</p> <h3 id="results">Results.</h3> <p><em>K. pneumoniae</em> sepsis was diagnosed in 81 patient with hematologic malignancies during 3 years study period. In 53 (65.4%) cases sepsis was caused by carbapenem-resistant <em>K. pneumoniae</em> isolates. Mortality in patients that received combination therapy with ceftazidime-avibactam and aztreonam was significantly lower (34.6%), than in patients that received other antimicrobial therapy (63.0%), p = 0.039. When ceftazidime-avibactam plus aztreonam therapy was started ≥7 days after the onset of infection the mortality rates in both groups were similar (p &gt; 0.05).</p> <h3 id="conclusions">Conclusions.</h3> <p>The incidence of carbapenem-resistance in <em>K. pneumoniae</em> sepsis in hematologic malignancies was 65.4% in the present study. Early administration of ceftazidime-avibactam and aztreonam combined therapy was associated with lower mortality (34.6%) comparing alternative antibiotic regimens (63.0%).</p> http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p375/ Fri, 20 Jan 2023 10:35:18 +0000 http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p375/ <h3 id="objective">Objective.</h3> <p>To study epidemiology and impact of colonization by multidrug-resistant Gram-negative bacteria (MDRGNB) on bloodstream infections (BSI) during allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The retrospective study included 288 patients received the first allo-HSCT between 2018 and 2019. The median age was 32 (18–66) years, male – 53% (n = 152). The majority of patients had acute leukemia – 62% (n = 178) and received transplant from matched unrelated – 42% (n = 120) or haploidentical donor – 26% (n = 75). Relapse of underlying disease at the moment of all-HSCT was registered in 23% (n = 66) of patients.</p> <h3 id="results">Results.</h3> <p>Colonization of non-sterile sites before allo-HSCT by at least one MDRGNB was detected in 28% (n = 64). In most cases resistance is due to extended spectrum beta-lactamases (ESBL) – 86% (n = 55), while carbapenemases in combination with ESBL were detected in 14% (n = 9) of patients. After allo-HSCT the colonization was significantly higher than before transplantation (n = 161, 56%, p = 0.001), mainly due to carbapenemase- and ESBL-producing bacteria – 73% (n = 118) (p = 0.001). BSI in the early period after transplantation developed in 26% (n = 76), and in 56% (n = 43) was caused by MDRGNB. The etiology of BSI included <em>K. pneumoniae</em> – 51% in mostly cases. The etiology of BSI was the same bacteria that colonized non-sterile sites 2 weeks before the detection bacteria in bloodstream in 69% (n = 30) patients. Colonization by MDRGNB was associated with the development of BSI (p &lt; 0.0001). The 100-day overall survival (OS) after all-HSCT was significantly lower in patients with colonization of non-sterile sites by MDRGNB compared with patients without colonization (60.6% vs 88.2%, p = 0.001).</p> <h3 id="conclusions">Conclusions.</h3> <p>Colonization of MDRGNB after allo-HSCT reached 56%. <em>K. pneumoniae</em> was predominant etiology in both colonization and bloodstream infections. Colonization by MDRGNB was associated with the development of BSI and decreased OS after allo-HSCT.</p> http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p369/ Fri, 20 Jan 2023 10:33:00 +0000 http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p369/ <h3 id="objective">Objective.</h3> <p>To investigate prevalence of the A2058G mutation in the Russian population of T. pallidum and its association with molecular subtypes.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We analyzed DNA isolated from 325 samples of clinical material obtained from patients of dermatovenereological treatment and prophylactic institutions in 6 federal districts of the Russia in the period from 2014 to 2021. Patients were diagnosed with primary syphilis of the genital organs, primary syphilis of other sites, or secondary syphilis of the skin and mucous membranes. DNA was isolated using the Proba-NK reagent kit (DNA-technology, Russia) according to the manufacturer&rsquo;s instructions. The presence of T. pallidum genetic material was confirmed by PCR with primers for the species-specific polA gene. Molecular typing was performed based on the analysis of polymorphic regions of species-specific T. pallidum genes. The primary decoding of the nucleotide sequences of the 23S rRNA gene fragment was carried out using the Sequencing Analysis 5.3.1 program. The analyzed fragments were aligned using the Mega 5 program.</p> <h3 id="results">Results.</h3> <p>Eight molecular subtypes of T. pallidum – 14d/f, 14d/g, 14b/f, 14c/f, 14i/f, 9d/f, 14b/g and 14e/f with stable dominance of subtype 14d/f – were identified in the Russian Federation in the interval 2014–2021. Three subtypes, 14d/g, 14b/g and 14b/f, carrying the A2058G mutation associated with azithromycin resistance, were identified.</p> <h3 id="conclusions">Conclusions.</h3> <p>Studies on molecular typing of T. pallidum strains in the Russia have shown significant population heterogeneity. Three sublines containing the A2058G mutation were shown to exist, one of which – 14b/f – is described as rare. The obtained data confirm the relevance of continuous monitoring of the emergence of resistant strains and the development of new mutations.</p> http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p361/ Fri, 20 Jan 2023 10:30:35 +0000 http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p361/ <h3 id="objective">Objective.</h3> <p>To assess practicing dentists who treat patients conservatively attitude to antibiotic therapy in general, the degree of awareness of the rules for prescribing antibiotics, approaches to prescribing antibiotics for various dental diseases and therapeutic and preventive manipulations.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The questionnaire was developed and an anonymous survey-questionnaire of 173 practical dentists conducting therapeutic reception of patients was carried out. The questionnaire included a list of diseases, therapeutic and prophylactic manipulations in which respondents consider the use of antibiotics indicated and questions to assess the respondents’ awareness of modern methods of antibiotic therapy and their views on the rules for prescribing antibiotics.</p> <h3 id="results">Results.</h3> <p>A statistical analysis showed that antibiotics using is considered inappropriate: in the conservative treatment of pulpitis after root canal filling (83.2%), during the conservative treatment of chronic apical periodontitis (66.5%, 95% CI: 59,4-73,5%), in patients with chronic catarrhal gingivitis (69.4%, 95% CI: 62,5-76,2%), in patients with chronic generalized periodontitis mild degree (without exacerbation) (75.1%, 95% CI: 68,7-81,6%), during professional cleaning of teeth (75.1%, 95% CI: 68,7-81,6%). The use of antibiotics is considered obligatory: in the treatment of acute apical periodontitis/exacerbation of chronic periodontitis (with suppuration from root canals) – 37.0% of respondents (95% CI: 29,8-44,2%); ulcerative necrotic gingivitis – 50.3% (95% CI: 42,8-57,7%), with chronic generalized periodontitis in the acute stage – 71.1% (95% DI: 64,3-77,9%), with professional cleaning of teeth in patients with concomitant pathology – 38.2% (95% DI: 30.9-45.4%)</p> <h3 id="conclusions">Conclusions.</h3> <p>Insufficient awareness of practical dentists, leading the conservative reception of patients, about modern methods of antibiotic therapy was revealed. The problems of the current dentistry situation are identified under such conditions of legally approved standards of care and clinical recommendations absence, as well as absence of organizational opportunities to conduct tests to determinate the sensitivity of microflora to antimicrobial drugs before prescribing antibiotics in outpatient dentistry are identified.</p> http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p295/ Fri, 20 Jan 2023 10:10:33 +0000 http://cmac-journal.ru/en/publication/2022/4/cmac-2022-t24-n4-p295/ <h3 id="objective">Objective.</h3> <p>To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male – 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male – 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male – 67%.</p> <h3 id="results">Results.</h3> <p>64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104–11.337], p = 0.02), and prolonged (&gt; 10 days) lymphopenia (OR = 8.770 [4.177–18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01).</p> <h3 id="conclusions">Conclusions.</h3> <p>IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p283/ Sat, 29 Oct 2022 10:37:57 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p283/ <h3 id="objective">Objective.</h3> <p>To study effects of bacteriophages on biofilm formation and formed biofilm by <em>S. aureus</em> isolated from patients with orthopedic infection.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 50 clinical strains of <em>S. aureus</em> were tested. Species identification was performed by MALDI-TOF MS, antibiotic susceptibility – in accordance with the EUCAST v21. Isolates susceptibility to bacteriophages «Sextafag» (Microgen, Russia) was determined by MPA medium. The antibacterial activity of phages against <em>S. aureus</em> ATCC 29213 and <em>S. aureus</em> ATCC 43300 was evaluated by growth kinetic curves. Biofilms of bacteriophage-sensitive <em>S. aureus</em> strains were formed according to the protocol described by O’Toole. Isolates were divided into categories in accordance with the Stepanovic criteria. The effects of bacteriophages on the formation of <em>S. aureus</em> biofilm were studied by co-incubation of phages and bacteria followed by calculation of the percentage inhibition relative to the control without the introduction of the phages. The effect of phages on 24-hour biofilms formed by staphylococci was also evaluated in comparison with the control.</p> <h3 id="results">Results.</h3> <p>Out of 50 clinical <em>S. aureus</em> strains studied, 43 isolates (86%) were susceptible to phages, including 22 MSSA and 21 MRSA. All phage-susceptible cultures were characterized by biofilm-forming ability of varying degree: 28% – weak biofilm producer, 35% – moderate, 37% – strong. Inhibition of biofilm formation was determined in all tested MRSA strains, while in 73% of isolates the index of biofilm formation inhibition was more than 80%, which exceeded this indicator for MSSA by 2.5 times. In turn, the destruction of the formed biofilm under the action of the bacteriophage was 72% for all <em>S. aureus</em>. In 57% of MSSA strains, the decrease in biofilm biomass in comparison with the control was more than 80%, while this indicator was 2 times higher than for MRSA.</p> <h3 id="conclusions">Conclusions.</h3> <p>The results demonstrated a high <em>in vitro</em> efficacy of bacteriophages against biofilm formation in <em>S. aureus</em>.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p274/ Sat, 29 Oct 2022 10:35:37 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p274/ <h3 id="objective">Objective.</h3> <p>To study spectrum of pathogens and the time to colonization of respiratory samples in patients with severe and critical COVID-19 as well as to analyze incidence of nosocomial infections and structure of prescribed antibacterial drugs.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The prospective observational study included patients aged 18 years and older with confirmed severe and critical COVID-19 from December 2021 to February 2022. During the first 48 hours and then every 2–3 days of hospitalization, a respiratory sample was collected: sputum, tracheal aspirate (if intubated), bronchoalveolar lavage (if bronchoscopy was performed) for microscopy and microbiological examination. Some patients were screened for invasive aspergillosis. Clinical and demographic data, comorbidities, pathogenetic therapy for COVID-19, antibiotic therapy, cases of probable/documented bacterial nosocomial infections, antibiotic-associated diarrhea, and hospital treatment outcomes were recorded.</p> <h3 id="results">Results.</h3> <p>A total of 82 patients were included in this study. Patients with lung parenchyma involvement of more than 50% by computer tomography predominated; most of them (77%) required intubation and mechanical ventilation due to progression of respiratory failure, and 76% of patients had a lethal outcome. During the first 48 hours, a respiratory sample was obtained from 47 patients; the rest of the patients presented with non-productive cough. No growth of microorganisms was detected in 31 (36.8%) cases; clinically significant pathogens were detected in 16 (19.5%) patients. A subsequent analysis included data from 63 patients with a sufficient number of samples for dynamic observation were used. During the first 3 days of ICU stay, the most common bacterial pathogens were <em>Klebsiella pneumoniae</em> without acquired antibiotic resistance and methicillin-susceptible <em>Staphylococcus aureus</em>. From 3rd day and afterwards, an increase in the proportion of <em>Acinetobacter baumannii</em>, other non-fermenting bacteria, and carbapenemresistant <em>Enterobacterales</em> was noted. Among the pathogens causing lower respiratory tract infections, <em>A. baumannii</em> and carbapenem-resistant <em>K. pneumoniae</em> were predominant pathogens and accounted for 76% of cases. Positive galactomannan test results were obtained in 4 cases.</p> <h3 id="conclusions">Conclusions.</h3> <p>The study confirmed importance of bacterial nosocomial infections in patients with severe and critical COVID-19. In the case of the development of nosocomial lower respiratory tract infections, empirical antimicrobial therapy should take into account the predominance of carbapenem-resistant Enterobacteria and <em>A. baumannii</em>, as well as the possibility of invasive aspergillosis.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p268/ Sat, 29 Oct 2022 10:34:13 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p268/ <h3 id="objective">Objective.</h3> <p>To study <em>in vitro</em> antimicrobial resistance and prevalence of the most clinically important carbapenemases genes in <em>Klebsiella pneumoniae</em> clinical isolates in Nizhny Novgorod.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 238 <em>K. pneumoniae</em> clinical isolates from upper and lower respiratory tracts, abdominal cavity, urogenital tract, and wound discharge were tested in this study. Species identification was done using WalkAway 96 analyzer (Siemens, Germany) with POS Combo Type 20 tablets (Beckman Coulter, USA) and Multiscan FC spectrophotometer (Thermo Scientific, Finland) with Microlatest tablets (PLIVA-Lachema, Czech Republic). Antimicrobial resistance was determined by discdiffusion method and using microbiological analyzer WalkAway 96 (Siemens, Germany). Minimal inhibitory concentrations for colistin were determined using the “MIC Colistin” kit (Erba Mannheim, Czech Republic). Detection of carbapenemases genes (KPC, OXA-48 group, IMP, VIM and NDM) was performed by RT-PCR using CFX-96 machine (Bio-Rad, USA) and commercial kits «MDR KPC/OXA-48-FL» and «MDR MBL-FL» (AmpliSens, Russia).</p> <h3 id="results">Results.</h3> <p>More than 90% of <em>K. pneumoniae</em> isolates in Nizhny Novgorod were resistant to III–V generation cephalosporins, 53.8% – to gentamicin, 71.2% – to ciprofloxacin, 81.2% – to co-trimoxazole, 88.1% – to ertapenem, 37.1% – to doripenem, 21.6% – to imipenem, 34.3% – to meropenem, 3.2% – to colistin. Genes of КРС-like carbapenemases were detected in 13.1% of isolates, OХA-48 – in 21.6%. Metallobeta-lactamases were not identified among tested isolates.</p> <h3 id="conclusions">Conclusions.</h3> <p>Currently, there are no antimicrobials that active against all <em>K. pneumoniae</em> isolates in Nizhny Novgorod. Carbapenems and polymyxins remain active against more than 50% of isolates.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p261/ Sat, 29 Oct 2022 10:32:12 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p261/ <h3 id="objective">Objective.</h3> <p>To present a case of successful treatment of a secondary bacterial infection caused by nondiphtheritic corynebacterium in a patient with severe COVID-19 and known beta-lactam intolerance.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A clinical case of infective endocarditis (IE) caused by Corynebacterium amycolatum in a 74-year-old patient hospitalized with severe COVID-19 is presented. Comorbidity (secondary immune deficiency due to active malignancy, chemotherapy courses; previous heart disease) and the need for immunosuppressive therapy were triggers for infection caused by a rare Gram-positive bacterium which is usually considered as clinically non-significant. The choice of empiric antimicrobial treatment was limited by the patient’s history of beta-lactam intolerance.</p> <h3 id="results">Results.</h3> <p>A multidisciplinary approach to medical care of the patient and alertness to secondary infections helped to diagnose IE in a timely manner and to choose effective antimicrobial therapy. Combination therapy with vancomycin and amikacin helped to make blood flow free from infection. The further switch to oral doxycycline in outpatient settings resulted in the patient recovery from the infection.</p> <h3 id="conclusions">Conclusions.</h3> <p>Under conditions of limited choice of drug therapy, it is critical to have access to modern microbiological diagnostics which make it possible to diagnose rare pathogens. A dialogue between treating physician and clinical pharmacologist helps to choose an empirical and targeted antimicrobial therapy with the best efficacy-safety ratio. There is a need to be alert to secondary infections, including those of atypical locations and courses and caused by rare or opportunistic pathogens.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p254/ Sat, 29 Oct 2022 10:30:16 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p254/ <h3 id="objective">Objective.</h3> <p>To evaluate the possibility of using the colistin disk chelator application (CDCA) method as simple and available screening tool for detection of mcr-1-mediated resistance to polymyxins in <em>Enterobacterales</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 47 colistin-resistant <em>Enterobacterales</em> isolates obtained in 2014–2020 within multicenter MARATHON study were included in the experiment. Colistin susceptibility testing was performed using Mueller–Hinton broth microdilution method according to ISO 20776-1:2006. Interpretation of the results was performed according to EUCAST v.12.0 clinical breakpoints. MCR-genes were detected by multiplex real-time PCR. Phenotypic screening for mcr-expression was performed on Mueller–Hinton agar by application of dipicolinic acid in concentration of 1,000 mcg/disk in 10 µL volume per disk and 0.5 M solution of EDTA in 5 µL volume per disk. Chelating effect was registered by differences in zone of growth inhibition around colistin disks with and without chelator. Measurements were performed with the help of caliper in millimeters. Statistical data processing was carried out in accordance with guidelines for statistical analysis in medical researches using MS-Excel tool.</p> <h3 id="results">Results.</h3> <p>In 25 of 47 included in the experiment enterobacteria isolates mcr-genes were detected by molecular method. MCR-detection by CDCA method identified the average difference value of the zones of growth inhibition for colistin and its combination with EDTA and DPA as 4.1 mm and 3.7 mm respectively for mcr-positive isolates and 1.7 mm and 1.2 mm respectively for mcr-negative isolates. Statistical analysis estimated that a difference of ≥ 3 mm in zone of growth inhibition for combination of colistin with one of the chelating agents when compared to colistin only allows us to conclude that a studied isolated carries mcr-1-mediated resistance to polymyxins. In addition, sensitivity of the test was 96% and specificity was 91% if DPA is used, while EDTA showed only 88% sensitivity and 77% specificity.</p> <h3 id="conclusions">Conclusions.</h3> <p>Proposed method appears as available technique for phenotypic screening of the <em>Enterobacterales</em> order for mcr-1-mediated resistance to polymyxins for practical laboratories in present conditions. The use of DPA is preferred because of better specificity and sensitivity rates.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p248/ Sat, 29 Oct 2022 10:28:03 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p248/ <h3 id="objective">Objective.</h3> <p>To determine whether the genes whose products are annotated as &laquo;MBL-fold metallohydrolase superfamily&raquo; are related to the proteins of the metallo-β-lactamase group.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Sequences of the 7 genes annotated as &laquo;MBL-fold metallohydrolase superfamily&raquo; were analyzed using the following resources: ClustalW, IQ-TREE, iTOL. Selection of the oligonucleotides for real-time PCR was performed using the Primer-BLAST resource. The level of gene expression was assessed using real-time PCR. MIC and MBC measuring was performed using cefepime and meropenem. The double-disc method with EDTA was used to determine the presence of MBL in the strain.</p> <h3 id="results">Results.</h3> <p>Analysis of the nucleotide sequences of the studied genes revealed that all of them were not included in the clade containing sequences of metallo-β-lactamase. In the exponential growth phase, mRNAs corresponding to the studied proteins were found. Determination of MIC and MBC revealed a low level of resistance to antibiotics of the β-lactamase group. The phenotypic test was negative for MBL in P. putida strain BS3701.</p> <h3 id="conclusions">Conclusions.</h3> <p>The investigated genes and corresponding proteins are not related to metallo-β-lactamases. They are not involved in the resistance of P. putida BS3701 to antibiotics of the metallo-β-lactamase group.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p236/ Sat, 29 Oct 2022 10:24:42 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p236/ <h3 id="objective">Objective.</h3> <p>To analyze frequency and identify genetic determinants of resistance of non-typhoid Salmonella (NTS) producing extended-spectrum β-lactamase (ESBL) isolated in the Russian Federation over the period 2016 to 2020.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Salmonella isolates, suspected to ESBL production, were collected by the All-Russia Reference Center of Salmonellosis during the national Salmonellosis surveillance program. Phenotypic resistance was determined by the broth microdilution method using G-I and G-II Mikrolatest®SensiLaTest MIC plates and by the double-disk synergy test. Whole genome sequencing was performed on the NextSeq platform (Illumina, USA), with subsequent de novo genome assembly (SPAdes 3.15.4), identification of plasmid types (MOB-suite v3.0.0), and identification of resistance genes (AMRFinderPlus v3.10.40).</p> <h3 id="results">Results.</h3> <p>Out of 1792 NTS isolates, 22 strains contained bla-genes of molecular classes A and D (blaTEM, blaCTX-M, blaSHV, blaOXA), one strain – AmpC (blaCMY-2) and three strains – combination ESBL of class A and AmpC (blaTEM, blaCMY-2, blaDHA). The frequency of occurrence of ESBL-producing Salmonella is 1.3%, AmpC – 0.2%. Additionally, strains were resistant to other non-β-lactam antibiotics. Six different types of plasmids were identified (IncI, IncFIB, IncC, IncHI2A, IncL/M and IncX1) in studied isolates. It was possible for 17 strains to identify location of resistance genes in plasmids of a certain type.</p> <h3 id="conclusions">Conclusions.</h3> <p>The frequency of occurrence of Salmonella strains producing ESBL and AmpC was 1.45%, which were found in sporadic cases of human diseases, as well as food and environmental objects were sources of isolation. The fact of detection of such strains among various NTC serotypes and a wide range of sources of isolation confirms the relevance of monitoring antimicrobial resistance of Salmonella strains in the future.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p220/ Sat, 29 Oct 2022 10:19:19 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p220/ <h3 id="objective">Objective.</h3> <p>To assess level and the structure of systemic antibiotic consumption in Russia over the period 2017 to 2021.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Data were collected and analysed in compliance with the standard protocol of the World Health Organization Regional Office for Europe by the means of ATC/DDD methodology for J01 group – antibacterials for systemic use. Consumption was calculated for outpatients and inpatients separately as a number of DDDs per 1000 inhabitants per day (DID) for the main classes of antibiotics and the agents with the highest or the most diverse consumption levels for the given period of time, and was based on the data of wholesale purchases and public tenders.</p> <h3 id="results">Results.</h3> <p>Antibiotic consumption in Russia in 2017, 2018, 2019, 2020, and 2021 was 16.6 DID, 14.3 DID, 14.8 DID, 19 DID, and 15.7 DID respectively. Penicillins, macrolides and lincosamides, and quinolones had the highest levels of consumption in outpatients. Prominent increase in outpatient consumption of antibacterials in 2020 was related to three agents: azithromycin, levofloxacin and ceftriaxone. Cephalosporins (mainly III–V generations), quinolones and penicillins had the highest levels of consumption in inpatients. Hospital consumption of meropenem, tigecycline, and vancomycin increased and amikacin and ciprofloxacin decreased over the duration of the study.</p> <h3 id="conclusions">Conclusions.</h3> <p>Levels of systemic antibiotic consumption in Russia for the period 2017 to 2019 were relatively low and consistent with the average means for European Union and European Economic Area countries. The steep increase in consumption in 2020 was probably due to the wide use of antibiotics for the management of COVID-19 patients. The results of the study can be of value for the development of targeted national antibiotic stewardship programs and awareness campaigns as well as for the analysis of trends of emergence and spread of antibiotic resistance.</p> http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p196/ Sat, 29 Oct 2022 10:03:20 +0000 http://cmac-journal.ru/en/publication/2022/3/cmac-2022-t24-n3-p196/ <h3 id="objective">Objective.</h3> <p>To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The retrospective study included 44 adult recipients (allogeneic – 33 [75%] and autologous – 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia – 18 (41%) and lymphoma – 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1–818 days), after HSCT – 507.5 days (14–3723 days). Overall and progression-free survival was assessed using the Kaplan–Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection.</p> <h3 id="results">Results.</h3> <p>Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1–3490 days). Twelve patients (27.2%) were in grade 3–4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1–2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1–88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes.</p> <h3 id="conclusions">Conclusions.</h3> <p>The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%.</p> http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p181/ Sat, 13 Aug 2022 16:54:20 +0000 http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p181/ <h3 id="objective">Objective.</h3> <p>Development of local clinical protocols for antibacterial therapy of COVID-19-associated bacterial pneumonia in the therapeutic department of the city clinical hospital based on an analysis of the treatment process in patients with COVID-19-associated pneumonia.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective analysis of 1382 cases of hospitalization in the therapeutic department of patients with COVID-19-associated pneumonia for the period from 2020 to 2021 was carried out. The structure of etiotropic therapy, the frequency and timing of microbiological studies of the biomaterial, the manifestations of the main markers of bacterial infection during dynamic monitoring of clinical and laboratory parameters in patients prescribed antibiotic therapy, as well as statistics of the stay of patients in the therapeutic department of the hospital were assessed. Based on the results obtained in the course of microbiological studies, an assessment was made of the microbial landscape of the lower respiratory tract of patients with an analysis of the sensitivity of strains of the leading microflora to a wide range of antibiotics.</p> <h3 id="results">Results.</h3> <p>The study found that the dominant flora in COVID-19-associated pneumonia in hospitalized patients was gram-negative bacteria – <em>K. pneumoniae</em>, <em>P. aeruginosa</em> and <em>A. baumannii</em> – their proportion was more than 50%. Among <em>K. pneumoniae</em> strains, 89.4% were ESBL producers, 63.5% of the strains were resistant to carbapenems, which with a high probability allows them to be considered carbapenemaseproducing strains. Among the strains of <em>P. aeruginosa</em>, the proportion of strains resistant to carbapenems and with a high degree of probability being strains – producers of carbapenemase was 41.1%. Among strains of <em>Acinetobacter</em> spp. these were 76.4%, and associated resistance to fluoroquinolones and aminoglycosides was also demonstrated. Gram-positive microorganisms were found in 34.3% of cases and were mainly represented by strains of <em>S. aureus</em> (74.9%), only 26.4% of strains of this pathogen were methicillin-resistant.</p> <h3 id="conclusions">Conclusions.</h3> <p>Microbiological monitoring conducted in 2020–2021 revealed the presence, among the pathogens of viral-bacterial pneumonia, at an early stage of hospitalization, a significant proportion of gram-negative bacteria with resistance of the MDR and XDR types. Based on the obtained microbiological data, starting empirical schemes for antibacterial therapy of secondary viral and bacterial pneumonia, which complicated the course of a new coronavirus infection COVID-19 caused by the SARS-CoV-2 virus, were developed and proposed.</p> http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p171/ Sat, 13 Aug 2022 16:52:12 +0000 http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p171/ <h3 id="objective">Objective.</h3> <p>To present the results of using in-house method for rapid identification of fungi from funguspositive bottles with routine conventional culture-based identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in patients with bloodstream infection.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Prospective study was performed from 2016 to 2019 at the National Research Center for Hematology, Moscow. During the study period, all blood cultures (BC) bottles obtained from hematological patients were incubated in the BACTEC FX system (Becton Dickinson, USA). Positive BC bottles were examined by Gram stain. In house method was used after Gram stain was positive for yeast cells or hyphae. For that, BC media was transfer from fungus-positive bottles into tube. In house method included series section steps consisted from centrifugation and extraction of fungal proteins by adding of sodium dodecyl sulfate. Routine conventional culture-based identification on Sabouraud with chloramphenicol agar (bioMerieux, France) for yeasts and on Sabouraud dextrose agar (Oxoid, UK) for molds was used simultaneously with the in house method.</p> <h3 id="results">Results.</h3> <p>During the study period, 16 fungus-positive bottles were obtained from which were isolated in monoculture 14 (87.5%) <em>Candida</em> spp.: <em>C. parapsilosis</em> (n = 5), <em>C. tropicalis</em> (n = 4), <em>C. albicans</em> (n = 3), <em>C. krusei</em> (n = 1), C. guilliermondii (n = 1), one (6.3%) Rhodotorula mucilaginosa and one (6.3%) Fusarium dimerum. The in house method resulted in 75% (¹²&frasl;₁₆) and 68.8% (¹¹&frasl;₁₆) identification rate at the genus and species level of fungi, respectively. The identification of fungi to species level was confirmed by conventional culture-based method in all cases. The median time from the start of vial incubation in BACTEC FX system to identification of fungi by in house method was less than conventional culture-based identification: 36 hrs 20 min vs 55 hrs 31 min (p = 0.028).</p> <h3 id="conclusions">Conclusions.</h3> <p>A high rate of correct direct species identification and significant reduction in time to verification of fungi from fungus-positive bottles by in house method were obtained. The proposed in house method should be recommended for use in real microbiology practice to reduce the time for submitting results of identification to clinical units.</p> http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p156/ Sat, 13 Aug 2022 16:46:39 +0000 http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p156/ <h3 id="objective">Objective.</h3> <p>To determine the current state-of-art of acquired resistance to antimicrobial drugs among <em>L. monocytogenes</em> strains associated with listeriosis in humans and food contamination in Moscow.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We used 39 <em>L. monocytogenes</em> strains isolated in Moscow in 2019–2021 from clinical material (n = 24) and food (n = 15). Resistance to 12 antibiotics of the first and second lines of defense was studied using disk-diffusion method. The parameters recommended for <em>L. monocytogenes</em> were used to interpret the results; in the absence of recommendations for <em>L. monocytogenes</em>, the criteria for <em>Staphylococcus aureus</em> and/or <em>Enterococcus</em> spp. were used.</p> <h3 id="results">Results.</h3> <p>All strains were susceptible to ampicillin, benzylpenicillin, erythromycin, vancomycin, imipenem, linezolid, and the amoxicillin/clavulanic acid. Resistance was observed to gentamicin (23%) as well as to meropenem, trimethoprim/sulfamethoxazole and ciprofloxacin (5%, 74% and 28% of strains, respectively). A total of 15 strains with multiple antibiotic resistance were identified (13 and 2 isolates were resistant to three and four antibiotics, respectively). Simultaneous resistance to trimethoprim/sulfamethoxazole, ciprofloxacin and levofloxacin was observed in 9 strains, 6 strains were resistant to gentamicin and trimethoprim/sulfamethoxazole, including 3 strains – to gentamicin, trimethoprim/sulfamethoxazole, levofloxacin, and 2 strains – to gentamicin, trimethoprim/sulfamethoxazole, ciprofloxacin. Comparison of the growth inhibition zones by ampicillin and benzylpenicillin in the studied strains with historical data on the strains isolated in Russia in 1950–1980 showed a significant downward shift in the size of growth inhibition zones. Comparison of the distribution of strains with different diameters of growth inhibition zones depending on the source of isolation did not show significant differences between clinical strains and strains of food origin isolated in 2019–2021.</p> <h3 id="conclusions">Conclusions.</h3> <p>A wide spread of acquired resistance was shown among <em>L. monocytogenes</em> strains of clinical and food origin isolated in Moscow in 2019–2021. Despite the fact that all strains were susceptible to penicillins, the distribution of growth inhibition zone diameters showed a significant shift towards decreasing sensitivity to ampicillin and benzylpenicillin in strains isolated in 2019–2021 compared with <em>L. monocytogenes</em> strains isolated in Russia before 1980.</p> http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p147/ Sat, 13 Aug 2022 16:42:43 +0000 http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p147/ <h3 id="objective">Objective.</h3> <p>To assess minimal inhibitory concentrations (MICs) of antimicrobials for <em>Mycobacterium avium</em> complex (MAC) mycobacteria isolated from patients in Ural Federal District of the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We determined MICs for 33 <em>M. avium</em> and 34 <em>M. intracellulare</em> strains isolated from 67 patients with mycobacteriosis or tuberculosis/mycobacteriosis co-infection during 2018– 2019. SLOMYCO Sensititre test-system was used for susceptibility testing to 12 antibiotics: amikacin, streptomycin, clarithromycin, ethambutol, rifabutin, rifampicin, ciprofloxacin, ethionamide, isoniazid, linezolid, moxifloxacin, and doxycycline. Mycobacteria isolates were categorized according to their MICs as “susceptible”, “susceptible with increased exposure to the drug”, and “resistant” using CLSI breakpoints (2018). Breakpoints for amikacin, clarithromycin, linezolid and moxifloxacin were available for <em>M. avium</em> complex, for ciprofloxacin, doxycycline, rifabutin, rifampicin – for slow growing nontuberculous mycobacteria other than MAC mycobacteria. Breakpoints for ethambutol, isoniazid, streptomycin and ethionamide were not available.</p> <h3 id="results">Results.</h3> <p>Rates of susceptibility of <em>M. avium</em> and <em>M. intracellulare</em> were: amikacin – 96.9% and 97.0%, clarithromycin – 84.8% and 97.1%, linezolid – 9.1% and 23.5%, moxifloxacin – 57.6% and 38.2%, respectively. Majority of <em>M. avium</em> and <em>M. intracellulare</em> isolates were resistant to ciprofloxacin, doxycycline, and rifampicin. Ethambutol MICs for 84.4% of <em>M. avium</em> and for 67.7% of <em>M. intracellulare</em> isolates were &gt; 8 mg/L. The majority of studied isolates (64.2%) were susceptible to at least three antimicrobials for the treatment of infections caused by MAC mycobacteria.</p> <h3 id="conclusions">Conclusions.</h3> <p>Macrolides and aminoglycosides were the most effective against MAC mycobacteria in our study. Use of macrolides in combination with rifabutin and amikacin or moxifloxacin and amikacin may increase treatment efficacy in infections caused by <em>M. avium</em> and <em>M. intracellulare</em>.</p> http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p139/ Sat, 13 Aug 2022 16:36:43 +0000 http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p139/ <h3 id="objective">Objective.</h3> <p>To determine resistant microorganisms carriage, the frequency and etiology of postoperative infectious complications in high-risk infants with congenital heart defects (CHD).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The retrospective analysis included 489 patients admitted for surgical treatment for CHD. The median age was 0.23 (0–12) months. Swabs were taken from the oropharynx and rectum for microbiological examination no later than 72 hours after admission (a total of 978 samples). The growth of resistant microorganisms (ESBL and/or carbapenemase-producing <em>Enterobacterales</em>, resistant non-fermentative Gram-negative bacteria, MRSA and VRE) was recorded.</p> <h3 id="results">Results.</h3> <p>Of 489 patients, 128 (26.2%) were colonized with resistant bacteria. The majority of patients were carriers of ESBL-producers (81.3%), in some cases (24%) with concomitant production of several carbapenemases. The rate of VRE carriage was 21.1%, in 8 cases – in combination with other resistant microorganisms. MRSA was detected in 1.6% of carriers, other multidrug-resistant microorganisms – in 3.9% of carriers. In early postoperative period, ¹⁴⁵&frasl;₄₈₉ (29.7%) patients developed infectious complications. The ventilator-associated respiratory tract infections were the most common. In most cases (73.8%) infectious complications were caused by ESBL producers, in 43.9% of cases those microorganisms also produced carbapenemases. Resistant non-fermentative Gram-negative bacteria caused postoperative infections in 4.8% of cases. The rates of MRSA and VRE in infants with infectious complications were 3.4% and 1.4%, respectively. There were no differences in the incidence of infectious complications in colonized and non-colonized patients – ⁴²&frasl;₁₂₈ (32.8%) versus ¹⁰³&frasl;₃₆₁ (28.5%), respectively (p = 0.6). Postoperative infectious complications were caused by resistant microorganisms in colonized patients significantly more often than in non-colonized patients – ⁴¹&frasl;₄₂ (97.6%) and ⁸²&frasl;₁₀₃ (79.6%) cases, respectively (p = 0.008).</p> <h3 id="conclusions">Conclusions.</h3> <p>It is confirmed the active process of the introduction of resistant microorganisms into the hospital with the possible development of complications of the corresponding etiology. Gram-negative bacteria with different mechanisms of antibiotic resistance present the greatest problem. In order to manage this process, it is advisable to screen hospitalizing patients with the implementation of the infection control measures.</p> http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p134/ Sat, 13 Aug 2022 16:34:06 +0000 http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p134/ <h3 id="objective">Objective.</h3> <p>To study the prevalence of pneumocystosis among heart recipients (persons awaiting heart transplantation), persons with heart transplantation (patients with orthotopic heart transplantation) and to determine the role of pneumocysts in the etiology of bronchopulmonary complications in them.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The paper presents an analysis of the results of a study of 94 samples of blood sera of patients who were treated at the Shumakov Institute of Transplantation and Artificial Organs of the Ministry of Health of Russia (Moscow). As a comparison group, samples were taken from 90 donors aged 18 to 60 years.</p> <h3 id="results">Results.</h3> <p>The detection of various markers of pneumocystosis made possible to establish the total number of infected among the examined and determine the stage of the disease in them. Total antibodies were found in a significant number of examined patients (donors, heart recipients, patients with OTTS. They were 2.1 times more often detected in patients with OTT (53.5%) than in the comparison group (23.3%). The indicators of heart recipients did not differ much from those of blood donors, and amounted to 25.0%. Active pneumocystis infection was most often detected in patients with OTT, which in 27.9% of cases was due to primary acute infection, in 2.3% – reactivation and in 3.5% – convalescence. Active pneumocystosis was diagnosed 2.7 times less frequently in OTT recipients than in patients after heart transplantation. All cases of pneumocystosis in them are associated with primary acute infection. It should be noted that the incidence of pneumocystosis among donors is practically absent, active infection was 2.2%, all cases are due to primary acute infection.</p> <h3 id="conclusions">Conclusions.</h3> <p>The identification of such a significant number of cases of active pneumocystosis in patients after heart transplantation gives grounds to carry out laboratory diagnostics on a regular basis, which will prevent the development of pneumocystis pneumonia.</p> http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p93/ Sat, 13 Aug 2022 16:27:03 +0000 http://cmac-journal.ru/en/publication/2022/2/cmac-2022-t24-n2-p93/ <h3 id="objective">Objective.</h3> <p>To evaluate safety of anti-interleukin drugs used as a pathogenetic therapy of COVID-19 as assessed by risks of infectious complications.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A systematic review of publications related to safety assessment of anti-interleukin drugs recommended as pathogenetic therapy in COVID-19 patients in terms of incidence of serious adverse events and adverse events of “Infections and Invasions” class and a meta-analysis of the data were performed.</p> <h3 id="results">Results.</h3> <p>The meta-analysis included 16 randomized and 3 non-randomized studies. The hazard ratio of serious adverse events between the comparison groups was 0.93 <a href="p = 0.1" target="_blank">95% CI 0.85; 1.01</a>, the hazard ratio of adverse event of “Infections and Invasions” class was 0.9 <a href="p = 0.09" target="_blank">95% CI 0.8; 1.02</a>, showing no differences in the incidence of those events.</p> <h3 id="conclusions">Conclusions.</h3> <p>This meta-analysis did not demonstrate statistically significant differences in the relative risks of serious adverse events and adverse events of “Infections and Invasions” class for the use of antiinterleukin drugs in COVID-19 patients.</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p83/ Mon, 07 Mar 2022 14:34:45 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p83/ <h3 id="objective">Objective.</h3> <p>To assess bacterial contamination of smartphone surfaces belonging to medical staff and medical students who provide round-the-clock medical care in Krasnoyarsk hospitals and who do not work in those institutions.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Bacterial contamination of 122 smartphones owned by medical staff and medical students was studied in the following groups: doctors (n = 31), nurses (n = 29), students, who work in MIs (n = 27), and students who do not work in MIs (n = 35). The study included a survey for all participants to assess frequency of their smartphones cleaning.</p> <h3 id="results">Results.</h3> <p>Every fifth smartphone (26 of 122) was found to be contaminated. Staphylococcus spp. were identified on the devices of 27.6% of nurses, 13% of doctors, 14.8% of students working in MIs, and 20% of students not working in MIs. <em>E. coli</em> strains were not found. However, four cultures belonging to <em>Acinetobacter</em> spp. with three samples belonging to the <em>A. baumannii</em> were isolated from nurses’ smartphones. According to the results of the survey, 18% (n = 22) of the study participants never clean their smartphones, including 3.5% (n = 1) of nurses, 9.7% (n = 3) of doctors, 22.2% (n = 6) of students who work in MIs and 34.3% (n = 12) of students who do not work in MIs. In general, healthcare workers (doctors, nurses, working students) disinfect their smartphones significantly more frequently (several times a day) than students who do not work in MIs (¹&frasl;₃ of these students never do this, (p ≤ 0.05)). About 88% of the responders who regularly clean their smartphones use alcohol or alcohol wipes.</p> <h3 id="conclusions">Conclusions.</h3> <p>It is necessary to strengthen control over the microbiological safety of healthcare institutions staff’s smartphones. Also, it is essential to strengthen medical students’ training on the issue of healthcare-associated infections dissemination mechanisms.</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p77/ Mon, 07 Mar 2022 14:31:36 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p77/ <h3 id="objective">Objective.</h3> <p>To assess effect of topical use of solution containing ferrous ions on efficacy of metronidazole therapy in women with recurrent urogenital trichomoniasis.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study enrolled 55 women aged of 20–30 years with recurrent trichomoniasis after failures of multiple standard of care regimens. All patients received oral (tablets) and intravaginal (1% gel) metronidazole therapy. Participants in the experimental group (29 women) received intravaginal therapy with a solution of ferrous ions at concentration which was determined as effective for potentiating metronidazole in a previous study. In the control group, saline solution was used. Biological samples for laboratory tests were collected prior to treatment and on treatment days 4, 8 and 22. Treatment efficacy was assessed by laboratory results (detection of T. vaginalis, leukocyte-epithelial index).</p> <h3 id="results">Results.</h3> <p>Concomitant use of solutions containing ferrous ions at concentration 8.96 mmol/L can increase frequency of successful treatment outcomes in recurrent trichomoniasis. T. vaginalis was detected at the end of therapy in 10.3% of patients from the experimental group and 69.2% of patients from the control group.</p> <h3 id="conclusions">Conclusions.</h3> <p>The concomitant use of metronidazole and solution containing ferrous ions makes it possible to increase the efficacy of therapy for Trichomonas infection. The results of the study allow us to consider topical use of iron-containing drugs to increase metronidazole treatment efficacy in recurrent trichomoniasis.</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p67/ Mon, 07 Mar 2022 14:28:51 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p67/ <h3 id="objective">Objective.</h3> <p>To analyze the structure and magnitude of the labor costs of various categories of personnel of the microbiological laboratory in their workplaces in order to standardize labor and calculate the labor intensity of the studies performed.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The assessment of the labor costs of the personnel of the microbiological laboratory was carried out by time-and-motion study in the workplaces of a microbiologist (bacteriologist), a medical laboratory technician (MLT), a microbiological media preparation technician. The author&rsquo;s &laquo;The method for researching the labor costs of staff of medical laboratory&raquo; was applied.</p> <h3 id="results">Results.</h3> <p>The lists and duration of standard manipulations of the labor process of the analyzed workplaces are determined, their classification by labor components was performed, on the basis of which the values of fixed and variable labor costs of the personnel and the labor intensity of microbiological studies were calculated. Workload modeling was performed for all categories of personnel depending on the change in the number of bacteriological tests performed. It is shown that at the moment the total annual labor costs of a microbiologist make up 34% of the full-time budget, a MLT – 61%, and a media preparation technician – 31%. The workload ratio at the workplaces &laquo;microbiologist / MLT / media preparation technician&raquo; with the existing number of tests corresponds to 1.0/1.⁷&frasl;₀.9. The full workload on the one rate, according to currently existing regulatory documents, can be achieved with a microbiologist – with a volume of 16.3 K, with a MLT – 10.5 K, and with a media preparation technician – 36.4 K tests in year.</p> <h3 id="conclusions">Conclusions.</h3> <p>Systematized data on the structure and magnitude of labor costs of the microbiological laboratory personnel workplaces were obtained. The high labor intensity of bacteriological tests and its variability depending on their types and volumes are demonstrated. The proposed approach allows not only to analyze the actual labor costs of different categories of microbiological laboratory personnel, but also makes it possible to effectively model the workload, take into account the actual overload of a laboratory specialist, and predict the need for staff units depending on the volume and quantitative ratio of the range of tests performed.</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p52/ Mon, 07 Mar 2022 14:24:52 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p52/ <h3 id="objective">Objective.</h3> <p>To determine spectrum and prevalence of genetic determinants of resistance to macrolides in <em>Mycoplasma genitalium</em> in a Russian patient population.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 873 M. genitalium-positive samples from five geographical regions of Russia were investigated over the period of 2009–2019 using the previously developed protocol of real-time polymerase chain reaction (allows detecting any nucleotide substitutions in the 23S rRNA gene of M. genitalium at positions 2058, 2059, and 2611). The results were confirmed using Sanger sequencing.</p> <h3 id="results">Results.</h3> <p>The most frequent mutations associated with resistance to macrolides in M. genitalium were the following: A2058G (60.5%) and A2059G (30.2%). The relatively rare mutations were A2058T (7%) and C2611T (2.3%). In the studied period, there was no trend to increase in frequency of mutations associated with resistance to macrolides. The study results are presented as an open project on the AMRcloud platform (<a href="https://amrcloud.net/ru/project/demares/" target="_blank">https://amrcloud.net/ru/project/demares/</a>).</p> <h3 id="conclusions">Conclusions.</h3> <p>Our data emphasize a need to introduce regular screening of M. genitalium-positive samples for the presence of macrolide resistance-associated mutations into clinical practice.</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p47/ Mon, 07 Mar 2022 14:19:23 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p47/ <h3 id="objective">Objective.</h3> <p>To perform genotyping of cytomegalovirus (CMV) phosphotransferase UL97 and investigate mutations associated with ganciclovir/valganciclovir (GCV/VGCV) resistance in children after allogeneic hematopoietic stem cell transplantation (HSCT) with confirmed CMV infection.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>This single-center prospective study was conducted from January 2020 to December 2021 and enrolled allogeneic HSCT recipients under 18 years of age with confirmed CMV infection. In case of possible GCV resistance, molecular genotyping with Sanger sequencing was performed. The search for mutations in the UL97 gene was carried out in the range of 425–670 codons.</p> <h3 id="results">Results.</h3> <p>Out of 168 patients with confirmed CMV infection, 72 patients met the criteria for possible resistance to GCV/VGCV. As a result of nucleotide sequencing of the CMV UL97 gene in 19 patients (11.3% of a total number of patients and 26.4% of patients meeting the resistance criteria) 11 genotypes of the following mutations were identified: H520Q, C592G, A594V, L595S, D605E, C603W, C607Y, C607F, M615V, M460V and E655K. The following mutations associated with resistance to HCV/VHCV: H520Q, C592G, A594V, L595S, C603W, C607Y, C607F, M460V were found in 12 patients (7% of a total number of patients and 9.7% of patients meeting the resistance criteria).</p> <h3 id="conclusions">Conclusions.</h3> <p>Due to a high frequency of detection of the mutant form of phosphotransferase UL97 in allogeneic HSCT recipients with confirmed CMV infection, it is important to implement monitoring of resistant-associated mutations in order to administer appropriate antiviral therapy</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p39/ Mon, 07 Mar 2022 14:17:08 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p39/ <h3 id="objective">Objective.</h3> <p>To create local antibiotic resistance surveillance system using the AMRcloud online platform to provide evidence base for activity of antimicrobials (AM) and antimicrobial resistance (AMR) epidemiology.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>This study was conducted at the Pirogov National Medical and Surgical Center (Moscow, Russia). The study is prospective, with two evaluations of the local AMR surveillance system (before and after the implementation of the AMRcloud online platform). Separately, the effects of implementing the AMRcloud platform were evaluated and the most frequent scenarios of using this system in hospital were studied.</p> <h3 id="results">Results.</h3> <p>With the help of the AMRcloud platform, which acts as one of the central links in the AMR surveillance process, a local AMR surveillance system was formed, providing continuity of historical data and evidence base on local AMR epidemiology with real-time access and bringing together specialists of various profiles.</p> <h3 id="conclusions">Conclusions.</h3> <p>Implementation of the AMRcloud online platform into multidisciplinary hospital operations enables the creation of a local evidence base on AM activity and AMR epidemiology, as well as reducing the labor costs of several crucial stages of AMR surveillance – data storage, analysis and exchange.</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p31/ Mon, 07 Mar 2022 14:14:48 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p31/ <h3 id="objective">Objective.</h3> <p>To analyze the features of local antibiotic resistance monitoring at hospitals in the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The study involved a survey of 305 institutions. The duration of data collection was 1 year (March 2020 – April 2021). The responses received were analyzed using the &laquo;R&raquo; programming language. Special packages were used for data processing and calculation of confidence intervals. Results were assessed by descriptive analysis with calculation of absolute and relative frequencies, and 95% confidence intervals according to the Wilson method. Frequencies were compared using Fisher&rsquo;s exact test. The significance level α was set at 0.05.</p> <h3 id="results">Results.</h3> <p>Hospitals at various levels of organization participated in the survey. Data on local epidemiology of antibiotic resistance was available for 54.1% of institutions. The use of computer tools to automate the collection and analysis of antibiotic resistance monitoring data was noted by 26.23%. The implementation of an antimicrobial management system in the work of a medical center was confirmed by 25.3%. Data on identification of pathogens and antibiotic susceptibility test were available in the LIS/MIS – 12.46%. Over 70% of participants indicated that they update interpretation criteria annually. Storage of the AST results for more than 1 year was implemented by over 90% of hospitals. Availability of local antimicrobial therapy protocols was confirmed by 34.75% of the respondents.</p> <h3 id="conclusions">Conclusions.</h3> <p>Access to data on the local epidemiology of antimicrobial resistance was unavailable for most specialists. Insufficient use of special tools to automate the collection and evaluation of antimicrobial resistance data has been identified. Implementation of an antimicrobial stewardship program and development of local antimicrobial therapy protocols were in a limited number of institutions. The data obtained indicate significant problems in the systemic organization of local antibiotic resistance monitoring.</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p23/ Mon, 07 Mar 2022 14:12:01 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p23/ <h3 id="objective">Objective.</h3> <p>To assess the actual practice of conducting clinical and economic studies of antimicrobial medicines included in the federal drug restrictive lists in the period from 2017 to the present.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>As part of the study, the lists of Vital and Essential Drugs in the period from 2017 to 2021 were analyzed for the identification of newly included Class J medicines «Antimicrobial drugs for systemic use» followed by a search for available clinical and economic studies.</p> <h3 id="results">Results.</h3> <p>Data were obtained on 8 clinical and economic studies for 6 drugs used for systemic antimicrobial therapy. The evaluation of available methodological approaches to the assessment of the economic effectiveness of antimicrobial drugs was carried out. Sensitivity analysis was used to test the stability of the results to changes in the effectiveness of strategies over time. Information about the effectiveness was based on international, more often pre-registration randomized clinical trials and their meta-analyses, without taking into account the epidemiological situation in the Russian Federation. For chronic infections, the indicator of the degree of patients’ adherence to therapy remains not taken into account. In the vast majority of studies, only direct medical costs are taken into account.</p> <h3 id="conclusions">Conclusions.</h3> <p>Evaluation of the economic effectiveness of the use of antimicrobial drugs requires, on the one hand, an expansion of the set of technical tools, taking into account the specific features of this group: the problem of bacterial resistance, epidemiological features of the spread of diseases, the importance of antibacterial therapy and prevention in the introduction of other medical technologies, on the other hand, a systematic analysis of the results of studies to assess the compliance of forecasts with the real economic effects of the introduction of medical technology</p> http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p14/ Mon, 07 Mar 2022 11:41:44 +0000 http://cmac-journal.ru/en/publication/2022/1/cmac-2022-t24-n1-p14/ <h3 id="objective">Objective.</h3> <p>To study risk factors, etiology, clinical signs and treatment outcomes of invasive aspergillosis (IA) and mucormycosis combination (IAM) in children.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective review of Saint-Petersburg register (1998–2021) of patients with IA was done and children with IAM were included. EORTC/MSGERG 2019 criteria were used for diagnosing and treatment results evaluation of invasive mycosis. We presented a clinical case of IAM in a child with acute lymphoblastic leukemia relapse.</p> <h3 id="results">Results.</h3> <p>A total of 12 children with IAM were included. They accounted 8% of all pediatric patients with invasive aspergillosis (n = 152). IAM was diagnosed in children with hematological malignancies and solid tumors from 4 to 16 years (median age – 11.5 years), mostly in girls (83%). Main risk factors of IAM were prolonged lymphopenia (75%, median 22 days) and neutropenia (67%, median 30 days) due to chemotherapy, systemic corticosteroids and/or immunosuppressive therapy, as well as HSCT. The predominant etiological agents of IA were Aspergillus niger (33%), A. nidulans (33%) and A. fumigatus (17%), of mucormycosis – Lichtheimia corymbifera (50%) and Rhizomucor spp. (50%). Based on EORTC/MSGERG 2019 criteria, «proven» mucormycosis was diagnosed in 83% of patients, «probable» – in 17%. «Probable» IA was found in 100% of patients. The most common clinical sites of IAM were the lungs (75%) and paranasal sinuses (43%), multifocal involvement was revealed in 33% of patients. Mucormycosis developed during antifungal therapy of IA in 83% of patients. Antifungal therapy of mucormycosis received 75% of patients (amphotericin B lipid complex – 89%, posaconazole – 78%, caspofungin – 33%), combined antifungal therapy – 33%, surgery – 50%; combination of surgical and antifungal treatment was used in 42% of patients. The overall 12-week survival was 77.8%. The use of combined surgical and antifungal treatment significantly improved the survival of children with IAM (p = 0.023).</p> <h3 id="conclusions">Conclusions.</h3> <p>Mucormycosis was diagnosed in 8% of children with IA. IAM developed mostly in patients with hematological malignancies (83%), prolonged lymphopenia (75%) and neutropenia (67%) against the background of chemotherapy, systemic corticosteroids and/or immunosuppressive therapy, as well as HSCT. In 83% of patients mucormycosis was diagnosed during antifungal therapy for IA. The development of IAM increased overall 12-week mortality (50%). The combination of antifungal therapy with surgical treatment significantly improved prognosis of IAM (p = 0.023).</p> http://cmac-journal.ru/en/publication/2021/4/cmac-2021-t23-n4-p404/ Thu, 27 Jan 2022 10:46:55 +0000 http://cmac-journal.ru/en/publication/2021/4/cmac-2021-t23-n4-p404/ <h3 id="objective">Objective.</h3> <p>To develop a technology for freezing and long-term storage of mycobacteria cultures and implement into a microbiological laboratory routine practice.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>For comparison between different condition, the media for freezing mycobacteria containing 0.9% NaCl or Middlebrook&rsquo;s 7H9 medium with the addition of glycerol at various concentrations: 0%, 4.0%, 20.0%, 50.0% (by final volume) was evaluated. To freeze suspensions of cultures, two methods were used: one – using a cryo-freezer (cooling rate of 1°C/min), the second – direct placement in a deep freeze at a temperature of -80°C. Suspension of a museum strain of <em>Mycobacterium tuberculosis</em> H37Rv was used for preparing suspension. The efficiency of the chosen storage method was assessed by the proportion of viable cells obtained after thawing the suspensions (total number of cells according to quantitative PCR data/number of CFU in Lowenstein-Jensen medium).</p> <h3 id="results">Results.</h3> <p>After storage under various conditions, from 1.2% to 16.9% of mycobacterial cells remained viable. The maximum percentage of viable cells of 16.9% (95% CI 8.6–42.4%) reached when stored in a freezer at a temperature of -80°C without using a cryo-freezer in a medium consisting of 0.9% NaCl with glycerol (20.0% by final volume). However, no statistically significant differences in viable cells were found in the medium containing 0.9% NaCl solution with the addition of 4.0%, 50.0% glycerol, as well as Middlebrook&rsquo;s 7H9 medium with and without glycerol.</p> <h3 id="conclusions">Conclusions.</h3> <p>A technology for long-term storage of mycobacterial cultures has been developed, based on freezing a cell suspension at a temperature of -80°C in a medium consisting of a 0.9% NaCl solution with the glycerol (20.0% volume fraction), which provides a high degree of cell viability preservation, is lowcost and can be easily integrated into the routine work of a microbiological laboratory.</p> http://cmac-journal.ru/en/publication/2021/4/cmac-2021-t23-n4-p400/ Thu, 27 Jan 2022 10:43:26 +0000 http://cmac-journal.ru/en/publication/2021/4/cmac-2021-t23-n4-p400/ <h3 id="objective">Objective.</h3> <p>To determine functional anti-LPS specific serum bactericidal antibody (SBA) and opsonophagocytic killing antibody (OPKA) activities in mice immunized with a pentavalent candidate vaccine against Shigella flexneri 1b, 2a, 3a, 6, Y (PF).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>(CBA x C57 B1/6) F1 mice were immunized with a PF. 14 days after the reimmunization, serum samples were collected and the level of specific IgG in them was determined by ELISA. The sera of mice immunized with individual modified lipopolysaccharides (mLPS), which are part of PF, were used for positive control. Serum from intact mice served as a negative control. The functional activity of serum antibodies was determined by the methods of SBA and OPKA assay. The result was evaluated by the percentage of bacteria killed.</p> <h3 id="results">Results.</h3> <p>In all experimental groups of mice, an increase in the titer of specific IgG is observed (p &lt; 0.05). The endpoint titer (ET) of anti-LPS S. flexneri 1b, 2a, 3a, 6, Y antibodies in the group of mice immunized with PF does not significantly differ from ET in the groups after immunizations with individual mLPS. At the same time, the indicators in the experimental groups are about 16 times higher than in the control. We determined a functional activity of S. flexneri-specific SBA and OPRA in mice immunized with PF. The rate of SBA killing was 54%, 66%, 35%, 60%, 60% for S. flexneri 1b, 2a, 3a, 6, Y serotypes, respectively. When OPKA killing in groups of immunized mice are 37%, 55%, 27%, 56%, 53% for S. flexneri 1b, 2a, 3a, 6, Y serotypes, respectively.</p> <h3 id="conclusions">Conclusions.</h3> <p>PF induces the production of specific anti-LPS IgG comparable to its individual components. The sera from PF immunized mice contain functional antibodies. Serum bactericidal and opsonophagocytic assay are effective for use in a mouse model.</p> http://cmac-journal.ru/en/publication/2021/4/cmac-2021-t23-n4-p388/ Thu, 27 Jan 2022 10:40:16 +0000 http://cmac-journal.ru/en/publication/2021/4/cmac-2021-t23-n4-p388/ <h3 id="objective">Objective.</h3> <p>To assess antimicrobial susceptibility, presence of resistance genes and determine the phenotypic groups of <em>K. pneumoniae</em>, <em>P. aeruginosa</em> and <em>A. baumannii</em> isolated from blood and cerebrospinal fluid of children with nosocomial infections in intensive care units from 2014 to 2020.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Minimum inhibitory concentrations of antibiotics were determined using the serial broth microdilution method. The identification of genes encoding the production of carbapenemases was carried out using hybridization fluorescence detection.</p> <h3 id="results">Results.</h3> <p>A total of 63 isolates of K. рneumoniae, 23 isolates of <em>P. aeruginosa</em> and 14 isolates of <em>A. baumannii</em> were tested in this study. <em>K. pneumoniae</em> was detected in 10.3%. <em>P. aeruginosa</em> was isolated at a frequency of 3.5%. <em>A. baumannii</em> accounted for 2.3%. The proportion of carbapenemresistant <em>K. pneumoniae</em> strains to meropenem and imipenem was 33% and 37%, respectively, of all isolates. Resistance to colistin and polymyxin in <em>K. pneumoniae</em> isolates was 33% and 24%, respectively. The production of carbapenemases OXA-48 was detected in 25 (89%) isolates. The presence of NDM, VIM, KPC carbapenemases was not detected. Among <em>P. aeruginosa</em>, 65% were resistant to meropenem, and 74% to imipenem. The highest activity against <em>P. aeruginosa</em> <em>in vitro</em> was exhibited by polymyxins. There were no strains that were insensitive to colistin. The detection rate of metallo-β-lactamases (MBL) in <em>P. aeruginosa</em> strains was 48%. Only VIM-type MBLs were identified. No other types of MBL have been found. <em>A. baumannii</em> was non-susceptible to meropenem in 64% and to imipenem in 71%. The highest <em>in vitro</em> activity against <em>A. baumannii</em> was shown by polymyxin. Rate of colistin resistance was 29%. The OXA-40 and OXA-23 genes were detected in 5 and 3 isolates, respectively.</p> <h3 id="conclusions">Conclusions.</h3> <p>There were high resistance rates to most antimicrobials among <em>K. pneumoniae</em>, <em>P. aeruginosa</em> и <em>A. baumannii</em> isolated from blood and cerebrospinal fluid in children with nosocomial infections. The increase in carbapenem resistance rates was also observed. Carbapenem resistance was due to OXA48 carbapenemases in <em>K. pneumoniae</em>, VIM-type MBLs in <em>P. aeruginosa</em>, and OXA-40 and OXA-23 carbapenemases in <em>A. baumannii</em>.</p> http://cmac-journal.ru/en/publication/2021/4/cmac-2021-t23-n4-p340/ Thu, 27 Jan 2022 10:20:58 +0000 http://cmac-journal.ru/en/publication/2021/4/cmac-2021-t23-n4-p340/ <h3 id="objective">Objective.</h3> <p>To analyze the incidence of HCV in patients of the «Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology» (Center), to compare with the overall population incidence of HCV, to identify risk factors and risk groups of HCV infection in the Center’s patients.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective analysis of the HCV incidence of HCV patients of the Center who were admitted to the Center between 01.07.2014 and 31.12.2020 was carried out. The study included patients aged 0 to 18 years, from all regions of the country, who had previously received therapy at their place of residence. Patient profile: hematological, oncological, immunological and surgical. The indications for testing for HCV were: hospitalization at the Center, stay at the center for 4–6 months, clinical indications. To assess risk factors and identify risk groups for HCV incidence, the main epidemiological aspects (age, sex, disease characteristics, geographical prevalence) were analyzed.</p> <h3 id="results">Results.</h3> <p>The incidence of HCV in the Center’s patients was 1.7%, which is 5 times higher than the incidence of the entire population of the country, and 50 times higher than that of the pediatric population. The highest incidence rate was observed in children aged 1 to 2 years – 2.8%. When comparing the risks of infection of the Center’s patients with the children&rsquo;s population of the country in age groups under 1 year, from 1 to 14 years, and from 14 to 19 years, an excess of 29, 24 and 9 times was revealed, respectively. When analyzing nosological forms, it was found that the highest HCV incidence was in patients with primary immunodeficiencies – 3.2%, while in patients with malignant neoplasms – 1.8%. The region with the highest prevalence of HCV in our study was the Far Eastern Federal District (9%), namely the Amur Region (14%).</p> <h3 id="conclusions">Conclusions.</h3> <p>Thus, the morbidity of patients with oncological and hematological profiles and patients with primary immunodeficiencies clearly demonstrates the problem of implementing the artificial mechanism of HCV transmission, which requires taking measures regarding the safety of invasive manipulations.</p> http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p330/ Sun, 31 Oct 2021 23:33:41 +0000 http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p330/ <h3 id="objective">Objective.</h3> <p>To study pathogenic factors (adhesion and biofilm formation) in <em>F. solani</em> isolated from skin of patients</p> <h3 id="materials-and-methods">Materials and methods.</h3> <p>A total of 86 strains of <em>F. solani</em> isolated from the skin of patients with a diagnosis of L30.3 “Infectious dermatitis” were selected. The reference strain <em>F. solani</em> F-819 was used for quality control. Samples were collected using a sterile cotton swab from an area of 5 × 5 cm. The primary incubation was at Saburo media (HiMedia, India). Determination of the adhesion of the strains was carried out in the previously developed model from a nitrocellulose plate. Biofilms were formed using the method by Pierce C. et al. in 96-well flat bottom polystyrene plates. The efficiency of <em>F. solani</em> biofilms was assessed by the optical density of the total biomass (staining with Cristal Violet extract) and exopolysaccharide matrix (staining with Congo Red extract).</p> <h3 id="results">Results.</h3> <p>The studied <em>F. solani</em> strains were divided into two groups: isolates from patients with acute course of the disease (group I, n = 54), and isolates from patients with chronic relapsing disease (group II, n = 32). The adhesion of microconidia of isolates from patients with a chronic form is higher compared to isolates from patients with an acute form (p = 0.013) and the reference strain (p = 0.007). 26 (81.2%) isolates from patients with chronic form of the disease and 19 (35.2%) isolates from patients with acute form had an increased ability to form biofilms. The total biofilm mass was higher in <em>F. solani</em> isolates from the patients with chronic disease than that in isolates from the patients with acute course of the disease, and already matured on the 4th day of incubation. An increase in number of exopolysaccharide matrix was observed in <em>F. solani</em> isolated from patients with chronic disease on the 5th day of incubation, which led to increase in total biofilm mass.</p> <h3 id="conclusions">Conclusions.</h3> <p>This study showed that <em>F. solani</em> can form biofilms. Significant differences in adhesion and biofilm formation between clinical strains of <em>F. solani</em> isolated from patients with various forms of the disease were found.</p> http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p305/ Sun, 31 Oct 2021 23:26:55 +0000 http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p305/ <h3 id="objective">Objective.</h3> <p>To study the genetic diversity of vancomycin-resistant <em>Enterococcus faecium</em> (VR-<em>E. faecium</em>) isolated from the blood culture in patients with hematological malignancies by multilocus sequence typing (MLST).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>VR-<em>E. faecium</em> isolated from the blood culture in hematological patients in 6 hospitals of 4 Russian cities (2003–2019) were evaluated. Susceptibility to vancomycin was tested by the broth microdilution method (CLSI, 2018). Vancomycin-resistance genes (vanA, vanB) were identified by polymerase chain reaction. Genotyping of VR-<em>E. faecium</em> was performed by MLST.</p> <h3 id="results">Results.</h3> <p>A total of 83 VR-<em>E. faecium</em> were examined. The vanA genes were detected in 71.1% (n = 59) VR-<em>E. faecium</em>, vanB genes – in 28.9% (n = 24). A total of 22 sequence types (STs) belonging to epidemic clonal complex CC17 were detected. The dominant sequence types were ST17 (19.3%), ST78 (18.1%), ST80 (16.9%), and comprised 54.3% VR-<em>E. faecium</em>. Other sequence types included 1 to 4 strains. VR-<em>E. faecium</em> carrying vanA, in comparison with VR-<em>E. faecium</em> vanB, significantly more often belonged to ST78 (23.7% vs. 4.2%, p = 0.0559, respectively) and ST80 (23.7% versus 0%, p = 0.0079, respectively) and less frequently to ST17 (6,8% versus 50%, р &lt; 0.0001). Circulation of 9 STs including «high-risk» clones ST17 and ST78 was detected during two study periods (2003–2011 and 2012–2019).</p> <h3 id="conclusions">Conclusions.</h3> <p>This study showed a genetic diversity of VR-<em>E. faecium</em> that was represented by 22 STs. All VR-<em>E. faecium</em> belonged to epidemic clonal complex CC17 and comprised «high-risk» clones ST17, ST78 and less common STs.</p> http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p293/ Sun, 31 Oct 2021 23:24:06 +0000 http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p293/ <h3 id="objective">Objective.</h3> <p>assessment of the evolution of the microbiological landscape of the hospital for the period of operation in 2020 into a pandemic of a new coronavirus infection in various departments, including intensive care units; change depending on the results of antibacterial therapy regimens.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>In a retrospective study, conducted from June to December 2020, in a multidisciplinary hospital working with COVID-19 infection, the resistance of isolated strains of microorganisms was analyzed in patients of different age groups. Resistance was assessed with test points in June and November 2020; depending on this, proposals were made to correct the internal (local) protocols of antimicrobial therapy.</p> <h3 id="results">Results.</h3> <p>The need for frequent and regular microbiological monitoring was confirmed. Further, we understood that the territories of the main and temporary hospital of the City Clinical Hospital No. 40 are heterogeneous and there are obvious differences both in structure and in the level of sensitivity. “In practice, these are two different hospitals”. Within the territories, the branches also differ from each other. When analyzing resistance in ICUs, it was revealed that within each hospital in each department, albeit similar in structure and profile of patients, there is a different level of resistance of strains.</p> <h3 id="conclusions">Conclusions.</h3> <p>The structure of sensitivity generally corresponds to the world data, but for some pathogens it differs significantly. Microbiological monitoring should be carried out not only inside the hospital, but also inside the department. The increase in consumption of carbapenems and protected cephalosporins requires a reassessment of the practice of using AMP in any covid hospital, due to the impact on the epidemic situation both in the ICUs and in the hospital.</p> http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p280/ Sun, 31 Oct 2021 23:18:21 +0000 http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p280/ <h3 id="objective">Objective.</h3> <p>To evaluate <em>in vitro</em> activity of biapenem and other clinically available carbapenems against Russian clinical isolates of <em>Enterobacterales</em>, <em>Pseudomonas aeruginosa</em> и <em>Acinetobacter</em> spp., including isolates with acquired fermentative mechanisms of resistance to β-lactams.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 3139 <em>Enterobacterales</em> isolates, 793 <em>P. aeruginosa</em> isolates and 634 <em>Acinetobacter</em> spp. isolates from hospitalized patients in 63 hospitals from 35 Russian cities were included in the study during 2018-2019. Minimal inhibitory concentrations (MIC) for biapenem and other antimicrobials were determined in accordance with ISO 20776-1:2006. Carbapenemases genes were detected by commercially available real-time PCR kits AmpliSens® MDR KPC/OXA-48-FL and AmpliSens® MDR MBL-FL (Central Research Institute of Epidemiology, Russia). Data analysis and reporting was performed using AMRcloud online platform (www.amrcloud.net).</p> <h3 id="results">Results.</h3> <p>For all tested <em>Escherichia coli</em> isolates MIC50/90 were 0.06/0.125 mg/l for biapenem, 0.¹²⁵&frasl;₀.25 mg/l for imipenem, and 0.06/0.06 mg/l for meropenem. When MIC50/90 for ertapenem (0.015/0.125 mg/l for all isolates tested) were comparable to those of biapenem, a greater number of nosocomial <em>E. coli</em> isolates had MIC &gt;4 mg/l for ertapenem (3.6%) than for biapenem (2.6%). MIC50/90 of <em>Klebsiella pneumoniae</em> for biapenem were 0.⁵&frasl;₁₆ mg/l, for both imipenem and meropenem – 0.⁵&frasl;₃₂ mg/l, for ertapenem – ²&frasl;₃₂ mg/l. Resistance to oxyimino-β-lactams had no significant influence on activity of biapenem against <em>Enterobacterales</em> isolates. For 321 carbapenemase-producing <em>K. pneumoniae</em> isolates (ОХА-48 – 63.9%, NDM – 27.7%) biapenem has shown no advantages over imipenem and meropenem. МПК50/90 for nosocomial and community-acquired <em>P. aeruginosa</em> isolates were ⁸&frasl;₆₄ mg/l and 0,⁵&frasl;₁₆ mg/l for biapenem, ⁸&frasl;₁₂₈ mg/l and ¹&frasl;₁₆ mg/l – for imipenem, ¹⁶&frasl;₆₄ mg/l and 0,⁵&frasl;₃₂ mg/l – for meropenem. All carbapenems, including biapenem, had very low <em>in vitro</em> activity against carbapenemaseproducing <em>P. aeruginosa</em> isolates. МПК50/90 of <em>Acinetobacter</em> spp. were ⁶⁴&frasl;₁₂₈ mg/l for biapenem, ⁶⁴&frasl;₁₂₈ mg/l – for imipenem, and ¹²⁸&frasl;₁₂₈ mg/l – for meropenem.</p> <h3 id="conclusions">Conclusions.</h3> <p>According to the MIC distributions and MICs50/90 values independently of the presence of fermentative mechanisms of resistance to β-lactams, <em>in vitro</em> activity of biapenem against Russian clinical isolates of <em>Enterobacterales</em>, <em>P. aeruginosa</em> and <em>Acinetobacter</em> spp. was comparable to those of imipenem and meropenem.</p> http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p264/ Sun, 31 Oct 2021 23:14:24 +0000 http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p264/ <h3 id="objective">Objective.</h3> <p>To assess the <em>in vitro</em> activity of ceftazidime-avibactam against clinical <em>Enterobacterales</em> and <em>Pseudomonas aeruginosa</em> isolates in various regions of Russia based on results of local susceptibility testing by disk diffusion method.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Overall, 160 laboratories located in 61 Russian cities participated in this surveillance during 2018-2020. All consecutive clinical isolates of <em>Enterobacterales</em> and <em>Pseudomonas aeruginosa</em> in each participating laboratory were included in the study. Ceftazidime-avibactam susceptibility testing was done by disc-diffusion method in accordance with current EUCAST recommendations. Susceptibility data for carbapenems and III-IV generation cephalosporins, as well as results of carbapenemases detection, were also reported, if available. All the data were recorded in electronic case report form developed on the OpenClinica online platform (www.openclinica.com). Data analysis and reporting were done using AMRcloud online platform (<a href="https://amrcloud.net/" target="_blank">https://amrcloud.net/</a>).</p> <h3 id="results">Results.</h3> <p>In total, we received information on antimicrobial susceptibility of 22,121 isolates, including 17,456 (78.9%) <em>Enterobacterales</em> and 4,665 (21.1%) <em>P. aeruginosa</em>. Less than 9% of <em>Enterobacterales</em> isolates were resistant to ceftazidime-avibactam. At the same time rates of resistance to ceftazidime, cefotaxime, cefepime, ertapenem, imipenem, and meropenem were 54.1%, 58.9%, 59.4%, 41.4%, 23.9%, and 21.3%. Among <em>Enterobacterales</em> the highest level of resistance to ceftazidime-avibactam was detected in <em>K. pneumoniae</em> (16.5%), lowest – in <em>E. coli</em> (2.1%). Some increase of resistance to ceftazidimeavibactam was noted during the study – from 7.8% in 2018-2019 to 9.6% in 2020 (p = 0.0001). Rate of resistance to ceftazidime-avibactam in <em>P. aeruginosa</em> was 33.1%. At the same time rates of resistance to ceftazidime, cefepime, imipenem, and meropenem were 51.1%, 54.5%, 50%, and 47.3%. During the study there was statistically significant decrease in resistance to ceftazidime-avibactam in <em>P. aeruginosa</em> (p = 0.0001). Resistance rates for all beta-lactams for both <em>Enterobacterales</em> and <em>P. aeruginosa</em> were higher in nosocomial isolates than in community-acquired isolates.</p> <h3 id="conclusions">Conclusions.</h3> <p>Ceftazidime-avibactam demonstrated significantly higher <em>in vitro</em> activity against <em>Enterobacterales</em> and <em>P. aeruginosa</em> Russian clinical isolates comparing with commonly used carbapenems and extended spectrum cephalosporins. Access for all study data available at the AMRcloud online platform (<a href="https://amrcloud.net/ru/project/cazavi-1-2/" target="_blank">https://amrcloud.net/ru/project/cazavi-1-2/</a>).</p> http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p220/ Sun, 31 Oct 2021 21:07:52 +0000 http://cmac-journal.ru/en/publication/2021/3/cmac-2021-t23-n3-p220/ <h3 id="objective">Objective.</h3> <p>To determine species, sequence-types, antimicrobial resistance and virulence genes in <em>Achromobacter</em> spp. isolates obtained from cystic fibrosis (CF) patients in Russia.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Samples (sputum, nasopharyngeal swab) from 168 CF patients from 48 regions were studied. Whole-genome sequencing (WGS) was performed on MGISEQ-2000 platform. SPAdes software, Galaxy, ResFinder, Integrall, PubMLST were used for analysis of WGS data.</p> <h3 id="results">Results.</h3> <p>A total of 18 strains of <em>Achromobacter</em> spp. were isolated from 16 of 168 CF patients.<em>Achromobacter xylosoxidans</em> was the most prevalent and detected in ¹³&frasl;₁₈ cases (72%). Studied <em>Achromobacter</em> spp. isolates belonged to 14 sequence types, including 8 new sequence types. An adaptive resistance gene carriage was a rare phenomenon (¹&frasl;₁₈ isolates).</p> <h3 id="conclusions">Conclusions.</h3> <p>The <em>Achromobacter</em> spp. colonization rate of respiratory system in CF patients in Russia corresponds to the data reported in other countries. <em>A. xylosoxidans</em> isolates were the most prevalent (72%). <em>Achromobacter</em> spp. isolates from CF patients in Russia and show a high clonal diversity.</p> http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p212/ Fri, 09 Jul 2021 11:45:07 +0000 http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p212/ <h3 id="objective">Objective.</h3> <p>To improve stool sample culture and isolation of anaerobic flora, including <em>Clostridioides difficile</em> in the routine microbiological laboratory practice at the children’s oncology hospital.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 517 stool samples collected from patients in children’s oncology hospital from 2013 to 2015 were studied. All samples were analyzed by ELISA for <em>C. difficile</em> toxins and by culture according to dedicated 5 schemes for isolation of anaerobic bacteria, including <em>C. difficile</em>. Statistical significance of differences in isolation rates between the studied groups (culture schemes) was assessed by Pearson test.</p> <h3 id="results">Results.</h3> <p>Culture in liver broth and covering with technical agar followed by culture on anaerobic agar yielded 100% isolation rate of toxigenic <em>C. difficile</em> strains. This culture scheme is also suitable for isolating concomitant anaerobic flora: non-toxigenic <em>C. difficile</em> strains, <em>Clostridium perfringens</em>, other <em>Clostridia</em> spp. and <em>Bacteroides</em> spp.</p> <h3 id="conclusions">Conclusions.</h3> <p>Use of the liquid accumulation medium and covering with technical agar make it possible to isolate anaerobic flora from stool samples and increase an isolation rate of toxigenic <em>C. difficile</em> strains to 100% of ELISA-positive samples.</p> http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p205/ Fri, 09 Jul 2021 11:42:25 +0000 http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p205/ <h3 id="objective">Objective.</h3> <p>To evaluate frequency and intensity of cefazolin inoculum effect among methicillin-susceptible staphylococci isolated from patients with skin infections.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 80 methicillin susceptible isolates of <em>Staphylococcus aureus</em> were identified by cefoxitin disk-diffusion test and negative results of real-time PCR for mecA gene. Inoculum effect was measured by broth microdilution test with two inocula with concentrations of 5 × 105 CFU/mL and 5 × 107 CFU/mL. The disk-diffusion test with cefoxitin was also performed. Penicillin susceptibility was determined by disk-diffusion method. Beta-lactamase blaZ gene was identified by real-time PCR.</p> <h3 id="results">Results.</h3> <p>The frequency of cefazolin inoculum effect in tested isolates was 30% which is consistent with data from different countries. The MIC values for concentrated inoculum reached CLSI breakpoint for cefazolin resistance in 2.5% of isolates. The isolates with inoculum effect and those without it had the similar MIC values for cefazolin in broth microdilution test for standard inocula and similar diameters of inhibition zone in disk-diffusion test with cefazolin. Penicillin resistance was more frequent in inoculum effect-positive isolates. Beta-lactamase activity is considered as a main cause of cefazolin inoculum effect in staphylococci. The beta-lactamase blaZ gene was identified in the majority of isolates with cefazolin inoculum effect, but it was also prevalent among inoculum effect-negative isolates.</p> <h3 id="conclusions">Conclusions.</h3> <p>Up to 30% of MSSA isolates from skin lesions in dermatological patients from SaintPetersburg are positive for cefazolin inoculum effect. Those isolates are usually characterized by penicillin resistance. Most of the cefazolin inoculum effect-positive isolates also carry beta-lactamase blaZ gene.</p> http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p117/ Fri, 09 Jul 2021 11:39:04 +0000 http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p117/ <h3 id="objective">Objective.</h3> <p>To review the basic principles and functionality of the AMRmap online resource.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The AMRmap platform was developed using the R programming language and various downloadable modules – packages. The current annually updated version of EUCAST clinical breakpoints was applied for determination of categories of susceptibility to antimicrobial agents. Descriptive analysis includes calculation of absolute and relative frequencies, median values, and confidence intervals using the Wilson method. Categorical variables are compared using Fisher&rsquo;s exact test and Holm correction method for multiple comparisons. The algorithms are used to visualize multiple comparisons, kernel regression for trend analysis, and algorithms for finding associative rules.</p> <h3 id="results">Results.</h3> <p>The developed surveillance system includes modules for filtering, analyzing and visualizing antibiotic resistance data. The filters allow creating a sample of data with a specific list of parameters. A tab-based separation of analysis and visualization options ensure efficient stepwise evaluation of results. Data saving and sharing functions are also provided.</p> <h3 id="conclusions">Conclusions.</h3> <p>This web-based informatics system provides a convenient way to AMR data from prospective microbiological surveillance studies in Russia. AMRmap can be accessed at <a href="https://amrmap.ru" target="_blank">https://amrmap.ru</a>.</p> http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p166/ Fri, 09 Jul 2021 11:16:13 +0000 http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p166/ <h3 id="objective">Objective.</h3> <p>To determine the concentration of colistin, preventing the selection of colistin-resistant mutants of <em>K. pneumoniae</em>, and to evaluate the effect of antibiotics of different groups on the development of mutational resistance to colistin.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Minimum inhibitory concentrations (MIC) of colistin were determined for 88 <em>K. pneumoniae</em> strains by the method of serial microdilutions in broth, and carbapenemase genes were detected. The selection of colistin-resistant subpopulations was performed on cation-adjusted MüllerHinton agar (MHA) with the addition of 16 mg/l colistin. Mutant prevention concentration (MPC) of colistin is determined on MHA containing 0, 1, 2, 4, 8, 16, 32, 64 and 128 mg/l of colistin. Also, MPCs of colistin were determined in the presence of a fixed concentration of the second antibiotic: clarithromycin (2 mg/l), azithromycin (2 mg/l), rifampicin (1 mg/l), clindamycin (0.5 mg/l), meropenem (8 mg/l), linezolid (2 mg/l), amikacin (1 mg/l), vancomycin (2 mg/l), doxycycline (2 mg/l).</p> <h3 id="results">Results.</h3> <p>All strains remained susceptible to colistin (colistin MIC 0.06–1.0 mg/l). Resistance to meropenem (MIC &gt; 8 mg/l) was detected in 48 strains (54.5%), 46 of them were carbapenemase producers: KPC – 6 strains (6.8%), OXA-48 – 26 strains (29.5%), NDM – 14 strains (15.9%). Growth of colonies on MHA with 16 mg/l of colistin was found for 96.6% of the strains. The frequency of mutational resistance occurrence ranged from 6 × 10-9 to 10-6 (median: 2 × 10-7). The mutational nature of colistin resistance was confirmed for 36.4% of the strains. The MPC values of colistin were in the range of 16–256 mg/l; (MPC50 32 mg/l, MPC90 256 mg/l) and significantly (32–1024 times) exceeded the MIC values. In the presence of 1 mg/l of rifampicin, the MPC of colistin decreased 4–64 times (MPC50 4 mg/l, MPC90 4 mg/l). In the presence of 2 mg/l of doxycycline, MPC of colistin decreased 2–64 times for all strains (MPC50 8 mg/l, MPC90 16 mg/l). The presence of linezolid (2 mg/l) and vancomycin (2 mg/l) did not significantly change MPC of colistin. Meropenem at a concentration of 8 mg/l had no significant effect on colistin MPC for carbapenemase-producing <em>K. pneumoniae</em> strains. None of the antibiotics lowered the MPC50 of colistin to its clinically achievable serum concentrations.</p> <h3 id="conclusions">Conclusions.</h3> <p>A high frequency of formation of mutational resistance to colistin in <em>K. pneumoniae</em> was revealed. The MPC values of colistin are outside the range of clinically achievable serum concentrations and may decrease in the presence of other antibiotics.</p> http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p138/ Fri, 09 Jul 2021 10:42:17 +0000 http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p138/ <h3 id="objective">Objective.</h3> <p>To determine type of cytomegalovirus (CMV) infection (reactivation of a virus strain that was present before transplantation or re-infection with another virus strain) in allogeneic hematopoietic stem cell recipients by sequencing.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Clinical and laboratory data of 179 recipients of allogeneic hematopoietic stem cells collected from 2014 to 2018 were analyzed for CMV DNA in clinical specimens before and after transplantation. A total of 14 patients (28 samples) were included in the study. The CMV UL139 gene encoding viral glycoprotein was chosen for virus genotyping and sequence alignment. The primers complementary to its conservative sites were used. The resulting DNA sequence was analyzed using nucleotide BLAST software (<a href="https://blast.ncbi.nlm.nih.gov/Blast.cgi" target="_blank">https://blast.ncbi.nlm.nih.gov/Blast.cgi</a>) and Genome compiler (<a href="https://designer.genomecompiler.com" target="_blank">https://designer.genomecompiler.com</a>). The type of infection was determined by comparing DNA sequences before and after transplantation.</p> <h3 id="results">Results.</h3> <p>All enrolled patients were anti-CMV-positive prior to transplantation, which indicates the presence of CMV infection. Therefore, none of the patients had a primary infection as a result of transplantation. Of 14 patients, high percentage of sequence alignment (~100%) was observed in 8 patients. For the other 6 patients, substantial differences in sequences which indicate the different genotypes and the different type of infection were found. However, there was no statistically significant difference in the time to viral DNA appearance after transplantation in patients with re-infection and reactivation (p &gt; 0.05), nor was there a statistically significant correlation between the type of infection (reactivation/re-infection) and the main diagnosis or transfusion load.</p> <h3 id="conclusions">Conclusions.</h3> <p>Reactivation of the previously registered viral strain and re-infection with another viral strain were equally probable (8 vs. 6 cases). There were no associations between the main diagnosis and the type of infection (reactivation/re-infection) possibly due to a small sample size. Time to post-transplantation CMV DNA detection in blood was longer for re-infection (median of 69.5 days) compared to reactivation (median of 27 days), but this difference was also non-statistically significant. In addition, there was no significant contribution of blood transfusion burden to the type of CMV infection, which may suggest the donor blood is not a source of the different strains.</p> http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p127/ Fri, 09 Jul 2021 10:27:46 +0000 http://cmac-journal.ru/en/publication/2021/2/cmac-2021-t23-n2-p127/ <h3 id="objective">Objective.</h3> <p>To estimate prevalence and antimicrobial susceptibility of circulated <em>S. pneumoniae</em> serotypes in adult population in different regions of the Russian Federation.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 500 isolates of <em>S. pneumoniae</em> obtained from patients with invasive pneumococcal disease (IPD), community-acquired pneumonia (CAP), sinusitis/acute otitis media (AOM) and healthy carriers from 29 centers were included in the study from 01 June 2019 to 15 January 2020. Re-identification, typing using real-time PCR with 27 primer pairs and antimicrobial susceptibility testing were performed in the central laboratory by standardized methods.</p> <h3 id="results">Results.</h3> <p>Among 50 isolates from patients with IPD, the following serotypes were detected: 3 (20.0%), 23F (10.0%), 6ABCD (8.0%), 19F (6.0%), 12ABF, 4, 7AF, 8, 9NL, 9VA, 15B (4.0% each), 1, 10A, 11AD, 14, 15AF, 18ABCF, 22AF, 33F/33A/37 (2.0% each). PCV-13 and PPV-23 covered 62.0% and 86.0% of those serotypes, respectively. Among 357 isolates from patients with CAP, the following serotypes were detected: 19F (12.3%), 6ABCD (11.5%), 3 (10.1%), 23F (5.9%), 14 (5.3%), 22AF (5.0%), 11AD (4.8%), 9NL (3.4%), 15AF (2.8%), 9VA (2.2%), 18ABCF (2.0%), 19A (1.7%), 12ABF (1.4%), 17F (0.8%), 16, 33F/33A/37, 7AF and 8 (0.6% each), 10A and 4 (0,3% each); serotypes were not specified due to the PCR typing protocol limitations for 106 (29.8%) isolates. PCV-13 and PPV-23 covered 51.9% and 68.7% of those serotypes, respectively. In patients with sinusitis/AOM (n = 48), serotypes were: 19F (18.8%), 6ABCD (16.7%), 23F (12.5%), 3 (12.5%), 18ABCF (6.3%), 11AD (4.2%), 14 (4.2%), 22AF (4.2%), 15AF, 4, 9VA (2.1% each). PCV-13 and PPV-23 covered 75.0% and 83.3% of those serotypes, respectively. In healthy nasopharyngeal carriers (n = 45), the following serotypes were detected: 19F (24.4%), 3 (17.8%), 6ABCD (17.8%), 11AD (13.3%), 23F (8.9%), 22AF (6.7%), 14 and 15AF (2.2% each). PCV-13 and PPV-23 covered 71.1% and 91.1% of those serotypes, respectively. Serotypes 14, 19F, and 19A were frequently resistant to three antibiotics – penicillin, erythromycin, and tetracycline. Resistance to respiratory quinolones was very low (0.7%) and detected among serotypes 14 and 9NL only. The majority of non-vaccine serotypes did not have substantial antimicrobial resistance problems.</p> <h3 id="conclusions">Conclusions.</h3> <p>Despite the relatively low number of isolates in all but CAP group and limitations of PCR typing protocol, results of our study support the use of pneumococcal vaccines (PPV-23 and PCV-13) in Russian adult population, with some advantages of PPV-23 over PCV-13.</p> http://cmac-journal.ru/en/publication/2021/1/cmac-2021-t23-n1-p100/ Fri, 16 Apr 2021 12:18:20 +0000 http://cmac-journal.ru/en/publication/2021/1/cmac-2021-t23-n1-p100/ <h3 id="objective">Objective.</h3> <p>To assess the etiology of infections, microbial associations and antimicrobial resistance in a burn intensive care unit.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A microbiological study of 1322 biological samples from 195 patients with extensive burns included 479 blood samples, 82 respiratory samples, 326 urine samples, and 435 wound samples. Antimicrobial susceptibility testing was performed, and coefficients of constancy and associativity (CA), as well as the Jaccard coefficient were calculated.</p> <h3 id="results">Results.</h3> <p>The etiology of infections was represented by: <em>Pseudomonas aeruginosa</em> – 23%, <em>Acinetobacter baumannii</em> – 19.1%, <em>Enterococcus faecalis</em> – 18.6%, <em>Klebsiella pneumoniae</em> – 8.2%, CoNS (coagulasenegative staphylococci) – 8.2%, <em>Staphylococcus aureus</em> – 7.1%, <em>Candida albicans</em> – 7.1%, Candida non-albicans – 3%, other species were isolated with a frequency of less than 2%. Majority of the above mentioned pathogens showed high associativity: non-fermenting rods (NFR), <em>S. aureus</em>, <em>Enterobacterales</em>, <em>E. faecalis</em>, Candida non-albicans formed associations in 60.0%, 88.8%, 83.0%, 83.3% and 65% of cases, respectively. The prevalence of methicillin-resistant strains of <em>S. aureus</em> and CoNS was 71% and 81%, respectively. CoNS showed higher resistance to fluoroquinolones and gentamicin compare to <em>S. aureus</em>: 42% vs 23%, 46% vs 29%, respectively (χ2 = 6.91; p = 0.086; χ2 = 6.58; p = 0.013). <em>E. faecalis</em> showed high resistance rates to aminoglycosides and fluoroquinolones (&gt; 60%). All Gram-positive isolates were completely susceptible to vancomycin, linezolid, tigecycline, and teicoplanin. Resistance rates of Gram-negative bacteria (NFR, <em>K. pneumoniae</em>) to penicillins, cephalosporins, carbapenems (for NFR), and aminoglycosides were high (from 60% to 100%). The most active antimicrobial against NFR was colistin. Resistance of <em>K. pneumoniae</em> isolates to carbapenems was 23%, while other enterobacteria were highly susceptible to carbapenems.</p> <h3 id="conclusions">Conclusions.</h3> <p>The implementation of the local microbiological monitoring made it possible to characterize the qualitative pathogen structure and antimicrobial resistance in our burns intensive care unit. This data will serve as the basis for improving of the infection control and antimicrobial stewardship.</p> http://cmac-journal.ru/en/publication/2021/1/cmac-2021-t23-n1-p92/ Fri, 16 Apr 2021 12:15:42 +0000 http://cmac-journal.ru/en/publication/2021/1/cmac-2021-t23-n1-p92/ <h3 id="objective">Objective.</h3> <p>To determine <em>in vitro</em> activity of thiamphenicol and other clinically available antimicrobials against clinical isolates of <em>Haemophilus influenzae</em>, <em>Streptococcus pneumoniae</em> and <em>Streptococcus pyogenes</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We included in the study 875 clinical isolates from 20 Russian cities during 2018–2019. Among tested strains, 126 were <em>H. influenzae</em>, 389 – <em>S. pneumoniae</em>, 360 – <em>S. pyogenes</em>. Antimicrobial susceptibility testing was performed using broth microdilution method according to ISO 20776-1:2006. AST results were interpreted according to EUCAST v.11.0 clinical breakpoints.</p> <h3 id="results">Results.</h3> <p>The minimum inhibitory concentrations (MICs) of thiamphenicol did not exceed 2 mg/L for 94.4% of <em>H. influenzae</em> strains (MIC50 and MIC90 were 0.5 and 1 mg/L, respectively). Thiamphenicol was active against 76.9% of ampicillin-resistant <em>H. influenzae</em> strains (MIC of thiamphenicol &lt; 2 mg/L). The MIC of thiamphenicol was in the range of 0.06–2 mg/L for 96.7% of <em>S. pneumoniae</em> strains (MIC50 and MIC90 were 0.5 and 2 mg/L, respectively). The MIC of thiamphenicol for 90.6% of <em>S. pneumoniae</em> strains with reduced susceptibility to penicillin (MIC of penicillin &gt; 0.06 mg/L) did not exceed 2 mg/L. A total of 88.1% of <em>S. pneumoniae</em> strains resistant to erythromycin were highly susceptible to thiamphenicol (MIC &lt; 2 mg/L). The MIC of thiamphenicol did not exceed 8 mg/L for 96.1% of <em>S. pyogenes</em> strains (MIC50 and MIC90 were 2 and 4 mg/L, respectively).</p> <h3 id="conclusions">Conclusions.</h3> <p>Thiamphenicol was characterized by relatively high <em>in vitro</em> activity, comparable to that of chloramphenicol, against tested strains of <em>H. influenzae</em>, <em>S. pneumoniae</em> and <em>S. pyogenes</em>, including <em>S. pneumoniae</em> isolates with reduced susceptibility to penicillin.</p> http://cmac-journal.ru/en/publication/2021/1/cmac-2021-t23-n1-p17/ Fri, 16 Apr 2021 11:49:23 +0000 http://cmac-journal.ru/en/publication/2021/1/cmac-2021-t23-n1-p17/ <h3 id="objective">Objective.</h3> <p>To review a literature published over the past 5 years and our own data on the etiology of lower respiratory tract infections (LRTI), antimicrobial resistance and its relationships between sepsis and choice of appropriate antibiotic therapy.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>National Nosocomial Infections Surveillance (NNIS) criteria were used to diagnose LRTI. A review of the articles regarding LRTI from the Russian and international English language journals published over 6 years was performed. Identification of microorganisms was performed by culture over the period of 2003–2013; since 2014, MALDI-TOF MS method was used for this purpose.</p> <h3 id="results">Results.</h3> <p>Despite the ongoing policy to limit the use of antimicrobial therapy in the ICUs, there is an increase in carbapenemase-producing isolates in the ICUs from 2.2% (2018) to 11.7% (2020, 9 months). Along with the trend to increase in carbapenemase-producing pathogens causing LRTI, their variability is also increasing. In particular, it applies to strains producing carbapenemases OXA-48 or combination of OXA-48 with KPC; with the trend to combined production of carbapenemase beginning at 2019.</p> <h3 id="conclusions">Conclusions.</h3> <p>Carbapenemase producers are becoming more widespread in the ICU settings, including the lower respiratory tract in mechanically ventilated patients. Practitioners didn’t get used to associate VAP with the Sepsis-3 criteria. The changes in etiology include the increased rate of carbapenem-resistant <em>Enterobacterales</em> and non-fermenting Gram-negative bacteria, primarily <em>Acinetobacter</em> spp., in Russia. It’s due to improved quality of respiratory support and increased consumption of carbapenems, tigecycline and polymyxins. Significant increase of OXA-48-producing pathogens is likely to be associated with a poor compliance with temporary guidelines on COVID-19 with regard to antibiotic therapy.</p> http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p314/ Mon, 04 Jan 2021 16:53:22 +0000 http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p314/ <h3 id="objective">Objective.</h3> <p>To evaluate effectiveness of the various approaches to fluoroquinolone susceptibility testing of Salmonella, including S. typhi, taking into account molecular resistance mechanisms.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The MIC values of ciprofloxacin were compared with the inhibition zone for pefloxacin disc, 5 mg (310 isolates) and nalidixic acid, 30 mg (420 isolates). MIC of ciprofloxacin was determined by gradient diffusion test and broth microdilution method. Muller – Hinton agar and Muller – Hinton broth, antibiotic discs and MICE-tests (Oxoid, UK) were used. Chromosomal mutations in QRDR of gyrA, gyrB, parC, and parE genes and plasmid-mediated quinolone resistance genes (qnr, aac-(6’)-1b etc.) were detected in 19 Salmonella isolates by analysis using ResFinder service (Center of Genomic Epidemiology). Genomic DNA libraries were prepared using the MiSeq Nextera XT Library Preparation Kit (Illumina, USA). WGS was performed on MiSeq (Illumina, USA) with MiSeq Reagent Kit v3 600 cycles (Illumina, USA). Genome assembly and analysis were performed using CLC Genomics Workbench 8.0 (Qiagen, USA).</p> <h3 id="results">Results.</h3> <p>Despite the high concordance of ciprofloxacin MIC values and the results of disc diffusion screening with pefloxacin (96.5% of isolates) and nalidixic acid (98.1% of isolates), the results obtained for some resistant isolates were inconsistent. When those isolates were tested by a single method, there was a possibility of incorrect susceptibility categorization. Discordant results were obtained for 19 isolates and had the objective reason (paradoxical resistance phenotype due to the plasmid-mediated resistance, qnrS) in 3 cases. Other discrepancies were noted when the values were equal to the clinical breakpoints: ciprofloxacin MIC – 0.06 mg/l, inhibition zone for pefloxacin – 24 mm. Repeated testing revealed the variations around the clinical breakpoints: the MIC values of 0.06–0.12 mg/l, and inhibition zone of 23 to 25 mm.</p> <h3 id="conclusions">Conclusions.</h3> <p>When performing fluoroquinolone susceptibility testing of Salmonella, it is reasonable to add the category “Area of Technical Uncertainty”: ciprofloxacin MIC value of 0.06 mg/l, and inhibition zone for pefloxacin of 23 to 25 mm. Two discs (pefloxacin and nalidixic acid) should be used for fluoroquinolone resistance screening by disk diffusion method.</p> http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p306/ Mon, 04 Jan 2021 16:51:39 +0000 http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p306/ <h3 id="objective">Objective.</h3> <p>To evaluate effect of 23S rRNA gene mutations in <em>Mycoplasma pneumoniae</em> on severity of community-acquired pneumonia (CAP) in young adult patients.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 42 case histories of young adult patients with CAP treated at the Smolensk military hospital over the period of 25 October 2017 to 25 December 2019 were reviewed. «AmpliSens® <em>Mycoplasma pneumoniae</em>/<em>Chlamydophila pneumoniae</em>-FL» real-time PCR kit was used to detect <em>M. pneumoniae</em> from nasopharyngeal swabs collected prior to antimicrobial therapy. Testing for 23S rRNA gene mutations conferring macrolide resistance was performed by real-time PCR melt curve analysis (patent no. 2646123) and confirmed by DNA sequencing.</p> <h3 id="results">Results.</h3> <p>All patients had a clinical picture of non-severe CAP on hospital admission. All patients were treated with standard doses of azithromycin or clarithromycin. No respiratory failure or any other complications were observed. Macrolide-resistant genotype of <em>M. pneumoniae</em> was detected in 4 (9.5%) patients. Clinical, laboratory and radiological resolution of pneumonia in all cases occurred on day 10– 16, regardless of the presence of macrolide-resistant genotype.</p> <h3 id="conclusions">Conclusions.</h3> <p>There were no differences in clinical course of severity between CAP caused by <em>M. pneumoniae</em> with 23S rRNA gene mutation and CAP caused by wild-type <em>M. pneumoniae</em> The presence of mutations in the 23S rRNA gene of <em>M. pneumoniae</em> did not worsen the clinical course of CAP.</p> http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p302/ Mon, 04 Jan 2021 16:50:00 +0000 http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p302/ <h3 id="objective">Objective.</h3> <p>To study the possibility of transferring multidrug resistant microorganisms through healthcare workers’ cell phones between medical institutions in Khabarovsk.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>It was a comparative prospective study to assess contamination of cell phones with multidrug-resistant microorganisms in a population (n = 30) and among intensive care unit (ICU) physicians (n = 60) in medical institutions. Antimicrobial susceptibility testing was performed by disc-diffusion method. A total of 514 healthcare workers from medical institutions of Khabarovsk were interviewed. The study enrolled 58.9% (n = 303) of physicians and 41.1% (n = 211) of nurses.</p> <h3 id="results">Results.</h3> <p>Microbial contamination of the physicians’ cell phones with extensively drug-resistant (16.7%; n = 10) and pandrug-resistant strains (6.7%; n = 4) was found to be significantly higher than that in the population.</p> <h3 id="conclusions">Conclusions.</h3> <p>Working in several medical institutions and the healthcare workers’ personal articles can be the ways of spreading resistant microorganisms.</p> http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p272/ Mon, 04 Jan 2021 16:37:29 +0000 http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p272/ <h3 id="objective">Objective.</h3> <p>To determine frequency of Staphylococcus isolation and antimicrobial resistance in hospitalized children with different types of infections.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Species identification and antimicrobial susceptibility testing in staphylococci were performed on a WalkAway 96 analyzer using Pos Combo type 20 tablets, and mecA gene detection was performed on a RotorGene 6000 amplifier with a set of AmpliSens MRSA-screen FL.</p> <h3 id="results">Results.</h3> <p>A total of 876 strains of staphylococci isolated in children&rsquo;s hospitals were tested. The species and antibiotic resistance of <em>Staphylococcus aureus</em> and coagulase-negative staphylococci were studied. The most common types of staphylococci were: <em>S. aureus</em> – 36.0%, <em>S. epidermidis</em> – 23.0%, S. haemolyticus – 19.7%, S. hominis – 14.0%. As many as 35.3% of isolates were methicillin-resistant, while 32.9% of methicillin-resistant <em>S. aureus</em> was detected, and 65.6% of methicillin-resistant strains were among the most frequently isolated coagulase-negative staphylococci. The mecA gene was detected in 97.1% of phenotypically methicillin-resistant strains. Antibiotic resistance of <em>S. aureus</em> and coagulase-negative staphylococci circulating in children&rsquo;s hospitals is very high. Two strains of <em>S. aureus</em> with intermediate resistance to vancomycin (MIC = 4 mcg/ml) and one <em>S. aureus</em> with resistance to linezolid (MIC = 8 mcg/ ml) were isolated. Among coagulase-negative staphylococci, two strains with intermediate resistance to vancomycin (MIC = 8 mcg/ml), two resistant to vancomycin (MIC = 16 mcg/ml), and 6 strains resistant to linezolid (MIC from 8 to 32 mcg/ml) were identified.</p> <h3 id="conclusions">Conclusions.</h3> <p>Antimicrobial resistance of staphylococci in children&rsquo;s hospitals does not depend on the species, more than half of the isolated isolates are methicillin-resistant. During the reporting period, staphylococci resistant to vancomycin and linezolid were identified, which requires resistance mechanisms to be determined.</p> http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p266/ Mon, 04 Jan 2021 16:34:54 +0000 http://cmac-journal.ru/en/publication/2020/4/cmac-2020-t22-n4-p266/ <h3 id="objective">Objective.</h3> <p>To investigate a candidemia outbreak caused by <em>C. parapsilosis</em> in a clinical unit of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (NMRC PHOI).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 35 isolates of <em>C. parapsilosis</em> obtained from clinically significant specimens and swabs, including hands of nursing staff of the NMRS PHOI, over the 2018-2020 were genotyped in this retrospective study. Identification of <em>C. parapsilosis</em> isolates was performed by microbiological methods. The clonal structure of <em>C. parapsilosis</em> isolates was investigated by polymerase chain reaction followed by fragment analysis of microsatellite repeats (short tandem repeats, STR markers).</p> <h3 id="results">Results.</h3> <p>The results of the study showed genetic diversity of the population of <em>C. parapsilosis</em> isolates over the 2018–2020 in the NMRC PHOI. A total of 27 genotypes were identified, one of which caused candidemia in 6 patients.</p> <h3 id="conclusions">Conclusions.</h3> <p>The study results confirmed the nosocomial candidemia outbreak and showed the fragment analysis of STR-markers may be used for epidemiological investigations of outbreaks in hospital settings.</p> http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p242/ Sun, 18 Oct 2020 14:57:37 +0000 http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p242/ <h3 id="objective">Objective.</h3> <p>To investigate the mortality rate, comorbidity prevalence, and etiology of community-acquired pneumonia (CAP) in elderly patient population.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Hospitalized elderly patients with CAP were distributed into the following age groups: 65–74 years (group I), 75–84 years (group II) and 85–94 years (group III). The patients’ medical records were used for determining comorbidities and mortality rate. In order to determine etiology of CAP, sputum or BAL samples were collected. A total of 171 isolates were identified using MALDI-TOF MS.</p> <h3 id="results">Results.</h3> <p>The mortality rates were 27.1%, 31.5% and 45.7% in age groups I, II, III, respectively. The most common concomitant diseases in all age groups were arterial hypertension (47.4%, 54.6%, and 62.8% for groups I, II, and III, respectively), chronic heart failure (45.7%, 50.9%, and 60.0%, respectively), and coronary heart disease (15.2%, 25.9%, and 24.3%, respectively). The most frequently isolated bacteria by age group were the following: group I – non-fermenting Gram-negative bacteria (NFGNB) (7.4%), <em>Enterobacterales</em> (6.6%), <em>S. aureus</em> (6.6%); group II – <em>Enterobacterales</em> (13.9%), <em>S. aureus</em> (5.6%), <em>Enterococcus</em> spp. (5.6%), NFGNB (2.8%); group III – NFGNB (15.4%), <em>S. aureus</em> (7.7%), <em>Enterococcus</em> spp. (7.7%), Enerobacterales (7.7%).</p> <h3 id="conclusions">Conclusions.</h3> <p>The mortality rates in elderly patients with CAP were high and varied from 27.1% in 65–74 years old patients to 45.7% in 85–94 years old patients. The most common comorbidities in all age groups were arterial hypertension (up to 62.8%), chronic heart failure (up to 60%), and coronary heart disease (up to 25.9%). The main pathogens causing CAP in elderly patient population were <em>Enterobacterales</em> and non-fermenting Gram-negative bacteria.</p> http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p237/ Sun, 18 Oct 2020 14:55:07 +0000 http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p237/ <h3 id="objective">Objective.</h3> <p>To characterize periprosthetic joint infection in patients undergoing a total hip and knee joint replacement.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 77 patients with periprosthetic infection following hip and knee joint replacement hospitalized in Grodno City Clinical Hospital were studied over the period of 2014-2018. Wound discharge, tissue samples, and fistula’s wall swab were used for microbiological tests. The analysis of surgical treatment of patients with deep periprosthetic knee and hip joint infection has been performed.</p> <h3 id="results">Results.</h3> <p>Periprosthetic infection after hip joint arthroplasty was observed in 32 (41.6%) patients, and after total knee joint arthroplasty in 45 (58.4%) patients. Surgical treatment was performed in 18 (56.3%) and 32 (71.1%) patients with periprosthetic infection following total knee and hip joint replacement, respectively. A total of 10 (31.2%) of 32 cultures from patients with periprosthetic infection after total hip joint replacement and 8 (17.8%) of 45 cultures from patients with periprosthetic infection after total knee joint replacement were positive. Overall, <em>Staphylococcus aureus</em> was detected in 9 (50%) of 18 positive cultures. Gram-negative aerobic bacteria (<em>Acinetobacter baumannii</em>, <em>Klebsiella pneumoniae</em> <em>Pseudomonas aeruginosa</em>) were detected in ⁴&frasl;₁₀ and ⁵&frasl;₈ of positive cultures from patients with periprosthetic infection of hip and knee joints, respectively.</p> <h3 id="conclusions">Conclusions.</h3> <p>The most common pathogens causing periprosthetic infection of hip and knee joints were <em>S. aureus</em> (50%) and Gram-negative bacteria. The surgical treatment was performed in 71.4% of patients with periprosthetic joint infection.</p> http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p231/ Sun, 18 Oct 2020 14:53:49 +0000 http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p231/ <h3 id="objective">Objective.</h3> <p>To assess efficiency of the “MIC-MICRO” kit developed in the Department of New Technologies of the Saint-Petersburg Pasteur Institute, on reference strains and clinical bacterial isolates.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>In order to assess the “MIC-MICRO” kit, several options of its execution were used, including different groups of antibiotics: aztreonam, amikacin, gentamicin, colistin, meropenem, nitrofurantoin, chloramphenicol, cefotaxime, ceftriaxone, ciprofloxacin, erythromycin. In order to determine the range of antibiotic values, the EUCAST-2020 database was used. The quality control of adsorbed antibiotics was carried out using reference strains: <em>Escherichia coli</em> ATCC 25922, <em>Staphylococcus aureus</em> ATCC 29213 and <em>Escherichia coli</em> NCTC 13846 (colistin-resistant). Acceptable and target ranges of MIC values for control strains are evaluated according to “Regular and extended internal quality control for determining MIC and disk diffusion according to EUCAST recommendations” (v10.0). A total of 28 clinical isolates of <em>K. pneumoniae</em> obtained from patients with nosocomial infections in St. Petersburg hospitals in 2018–2019 was used in the study. The coordination of test results was obtained in accordance with GOST R ISO 20776-1-2010. Susceptibility testing results were interpreted in accordance with EUCAST recommendations (v10.0).</p> <h3 id="results">Results.</h3> <p>The MIC values in relation to the reference strains obtained using the “MIC-MICRO” kit were determined in the range of recommended values of the EUCAST-2020 standard. The results obtained in relation to clinical isolates of <em>K. pneumoniae</em> showed that the sensitivity categories determined using the developed kit and the serial microdilution method were the same for all the studied strains. The percentage of colistin-resistant isolates (MIC &gt; 2 mg/ml) in the serial microdilution method and determined using the “MIC-MICRO” kit was 35.7%. The percentage of susceptible strains was also similar for two types of methods (64.3%).</p> <h3 id="conclusions">Conclusions.</h3> <p>Colistin susceptibility testing of <em>K. pneumoniae</em> strains using the “MIC-MICRO” diagnostic kit and the reference serial microdilution method in a tablet, showed comparable results. Diagnostic efficiency, ease to use and simple interpretation of results make it possible to use the developed “MIC-MICRO” kit in clinical laboratory practice.</p> http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p221/ Sun, 18 Oct 2020 14:52:28 +0000 http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p221/ <h3 id="objective">Objective.</h3> <p>Assessment of bacterial identification effectiveness in clinical microbiology laboratory using the MALDI-MS based system BactoSCREEN.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Bacteriological testing was done by the cultivation on Сolumbia agar with 5% of sheep blood (at 37°C for 24 hours). Colonies for identification were selected based on their growth pattern, type of hemolysis, morphology and consistency. The species identification was done by the MALDI-MS using the microbiology analyzer BactoSCREEN. Apart from MALDI-MS, we used morphology and biochemical methods for species identification when necessary. Serological tests were used for serovar and biovar identifications.</p> <h3 id="results">Results.</h3> <p>A total of 85945 bacterial identifications was performed in 2018. When compared to 2017, the throughput of the laboratory increased ten times. A total of 23252 isolates were obtained in the previously mentioned period. A single identification took 2.98–13.22 minutes including time for supporting procedures, whereas the staff time for one identification itself constituted an average of 1.55 minutes. When compared to manual methods, introduction of mass-spectrometry allowed us to achieve 3.5-fold decrease of the staff time in the average. Therefore, annual labor saving in terms of staffing corresponds to 11 full-time positions.</p> <h3 id="conclusions">Conclusions.</h3> <p>In view of high throughput, analysis speed, simplicity and low cost of sample preparation, MALDI-MS identification fits well into the practice of clinical microbiology laboratory, especially when large-scale screening studies of bacterial cultures are required. The use of MALDI-MS is likely to be most promising when carrying out microbiological monitoring that is traditionally associated with large number of samples and wide range of microorganisms detected.</p> http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p212/ Sun, 18 Oct 2020 14:51:10 +0000 http://cmac-journal.ru/en/publication/2020/3/cmac-2020-t22-n3-p212/ <h3 id="objective">Objective.</h3> <p>To determine the level of basic knowledge of senior students of medical universities in the rational use of AMP.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Analysis of an anonymous multicenter survey in the framework of the “KANT” project (the full name of the project is “Physicians’ (Students ’) knowledge in antimicrobials usage”), conducted in 2018–2019 in 6 cities of Russia and Kyrgyzstan.</p> <h3 id="results">Results.</h3> <p>The study revealed a low level of knowledge of senior students in the field of antibiotic therapy and the empirical use of AMP. The best results are shown by students when answering questions “time interval for evaluating the effectiveness of starting antimicrobial therapy”, “rationality and the period of changing AMP with a positive clinical effect”, and “choice of tactics for treating acute tonsillitis/pharyngitis”; the worst – for questions “choice of first-line AMP in the treatment of various infections”, “choice of adjuvant drugs for bacterial infections of the respiratory tract”, and “determination of irrational combinations of AMP”.</p> <h3 id="conclusions">Conclusions.</h3> <p>According to the results of this study, senior students showed a low level of knowledge in the basic issues of the rational use of AMP and the principles of antibiotic therapy in general, which indicates the urgent need for additional educational activities among this category of respondents and an increase in the number of academic hours in the disciplines “Pharmacology” and “Clinical” pharmacology &laquo;in universities.</p> http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p155/ Thu, 28 May 2020 11:22:01 +0000 http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p155/ <h3 id="objective">Objective.</h3> <p>To identify bacterial interactions at the site of infection in cystic fibrosis patients and to assess their possible effects on the course of infection.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The following strains were used in this study: <em>Alcaligenes faecalis</em> LGBP strain, isolated from the environment; clinical isolates of <em>Pseudomonas aeruginosa</em>; <em>Achromobacter xylosoxidans</em>, <em>Acinetobacter baumannii</em>, <em>Alcaligenes faecalis</em>, and <em>Bacillus subtilis</em> strains; the standard laboratory <em>P. aeruginosa</em> PAO1 strain and its lysogens by temperate bacteriophages of various species, and its phageresistant mutants. Imaging and evaluation of the effects of bacterial interaction was performed in an <em>in vitro</em> co-infection with <em>A. faecalis</em> LGBP and the tested strains.</p> <h3 id="results">Results.</h3> <p>The bacteria of <em>A. faecalis</em> which are often involved in the lung co-infection in cystic fibrosis have been shown to stimulate the growth of most of the tested <em>P. aeruginosa</em> strains, as well as bacteria of some other species (for example, <em>B. subtilis</em>). The interspecies interactions pattern depends primarily on the strain of <em>A. faecalis</em> and physiological features of the infecting <em>P. aeruginosa</em> strains. When growing concurrently, the contacts between bacteria may change both the physical properties of the contacting bacteria surface (propagation rate) and the course of biochemical reactions in the contacting bacteria (occurrence of pigmentation, change in auto-plaquing pattern, reduction in alginate production).</p> <h3 id="conclusions">Conclusions.</h3> <p>The results suggest that visually recognizable interactions are similar to the interactions of <em>A. faecalis</em> LGBP, exhibited <em>in vitro</em> with clinical isolates of <em>P. aeruginosa</em>, may influence on the course of chronic infections and their treatment results. Expanding of model studies of bacterial interspecies interactions may contribute to better understanding of their molecular mechanism that may be useful for optimizing therapy</p> http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p149/ Thu, 28 May 2020 11:11:04 +0000 http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p149/ <h3 id="objective">Objective.</h3> <p>To investigate a nasopharyngeal carriage and serotypes of <em>S. pneumoniae</em> in children aged 3 to 6 years from day-care centers in Smolensk.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 245 isolates of <em>S. pneumoniae</em> from 1027 nasopharyngeal swabs from healthy children attending day-care centers was tested. Identification of <em>S. pneumoniae</em> was performed according morphological, cultural and antigenic characteristics (Slidex pneumo-Kit, bioMeriеux, France), susceptibility to optohin and bile. Extraction of <em>S. pneumoniae</em> DNA (338) from nasopharyngeal specimens and cultures was performed using nucleic acids extraction kit AmpliSens® DNA-sorb-В (Interlabservice, Russia). Molecular typing was performed using CDC-recommended PCR method with 22 pairs of primers.</p> <h3 id="results">Results.</h3> <p>Children without signs of infection diseases from 14 day-care centers were examined, whose parents have signed an informed consent. There were 245 (24.0%) isolates of <em>S. pneumoniae</em> from 1027 specimens of nasopharynx’s swabs. The partly vaccinated with PCV13 were children aged 3–4 years – 311 (30.3%), in 95 children were healthy carriage (38.2%) of <em>S. pneumoniae</em>. The majority of children under 4 years (⁷¹⁶&frasl;₆₉.7%) were non vaccinated, healthy carriage of <em>S. pneumoniae</em> were 216 (29.3%). The predominant serotypes of <em>S. pneumoniae</em> in partly vaccinated children were: 3 (9.8%), 6AB (17.9%), 19F (13.8%), 11AD (12.2%), 23F (5.3%), 19A (2%), 18ABCF (1.6%), 14 (2%), 9AV (1.2%), 6CD (0.8%). The coincidence of <em>S. pneumoniae</em> serotypes in vaccinated children and included in PCV13 were 54%. The most common serotypes of <em>S. pneumoniae</em> in non-vaccinated children were: 11AD (12.2%), 15A/F (2%), 23A (2%), 22AF (0.4%), 19A (1.3%), 33FA/37 (1.6%) and non-typeable serotypes (27.8%).</p> <h3 id="conclusions">Conclusions.</h3> <p>The low coverage of pneumococcal vaccine in children under 6 years shows the initial process of its implementation in Health Care. We detect the reduction of vaccine serotypes in children with incomplete immunization (54%) and notable increase in non-typeable serotypes (27.8%) in nonvaccinated children.</p> http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p143/ Thu, 28 May 2020 11:08:59 +0000 http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p143/ <h3 id="objective">Objective.</h3> <p>To evaluate resistance rates to carbapenems and III–IV generation cephalosporins among gramnegative bacteria, including production of carbapenemases and extended-spectrum beta-lactamases (ESBL).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 460 gram-negative bacteria isolated from hospitalized patients aged 1 to 85 years from 8 medical institutions of Rostov-on-Don and the region from April 2018 to December 2019 were tested by conventional microbiological methods. The most common acquired carbapenemases genes were determined by real-time PCR using commercial kits (Central Research Institute of Epidemiology, Russia).</p> <h3 id="results">Results.</h3> <p>The tested isolates included 180 (39.1%) isolates of <em>K. pneumoniae</em>, 87 (18.9%) – <em>E. coli</em>, 101 (22.0%) – <em>A. baumannii</em> and 92 (20.0%) – <em>P. aeruginosa</em>. <em>K. pneumoniae</em> and <em>E. coli</em> isolates exhibited the high resistance rates to cefotaxime – 96.7% and 71.2%, to ceftazidime – 95.5% and 54.0%, and to cefepime – 95.5% and 54.0%, respectively. ESBL production was detected in 35.0% and 78.2% of <em>K. pneumoniae</em> and E.coli isolates, respectively. <em>K. pneumoniae</em> and <em>E. coli</em> isolates were resistant to imipenem, meropenem, and ertapenem: 57.8% and 3.4%; 55.0% and 2.3%; 60.0% and 4.6%, respectively. Carbapenemase production was detected in 27.8% of <em>K. pneumoniae</em> and 4.6% of <em>E. coli</em> isolates. The most common beta-lactamases were metallo-beta-lactamases (NDM) and serine carbapenemases (OXA-48). <em>A. baumannii</em> isolates showed the high resistance rates to imipenem and meropenem (87.1% and 85.1%). The most common beta-lactamases were metallo-beta-lactamases (NDM) and serine carbapenemases (OXA-²⁴&frasl;₄₀ and OXA-23). <em>P. aeruginosa</em> isolates also showed the high resistance to carbapenems – imipenem (61.9%) and meropenem (58.7%). The most common betalactamases were metallo-beta-lactamases (VIM) and GES-5.</p> <h3 id="conclusions">Conclusions.</h3> <p>The results of this microbiological study indicate the extremely high prevalence of aerobic gram-negative bacteria in different infections. <em>A. baumannii</em>, <em>P. aeruginosa</em>, <em>K. pneumoniae</em> and <em>E. coli</em> isolates being resistant to third- and fourth-generation cephalosporins and carbapenems are particularly dangerous, especially due to production of ESBL and carbapenemases. The most clinically important are OXA and NDM beta-lactamases.</p> http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p128/ Thu, 28 May 2020 11:05:08 +0000 http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p128/ <h3 id="objective">Objective.</h3> <p>To reveal antibiotics being capable of potentiating the antimicrobial activity of colistin against multidrug- and extensively drug-resistant strains of <em>Klebsiella pneumoniae</em>, <em>Acinetobacter baumannii</em> and <em>Pseudomonas aeruginosa</em>.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The minimum inhibitory concentrations (MIC) of colistin alone and in combination with fixed concentrations of antibiotics of different groups were determined for 272 multidrug- and extensively drug-resistant strains of <em>K. pneumoniae</em>, <em>A. baumannii</em> and <em>P. aeruginosa</em>. Bactericidal activity of colistin, carbapenems, clarithromycin and their combinations were also determined at fixed PK/PD breakpoint concentrations of antibiotics.</p> <h3 id="results">Results.</h3> <p>Potentiation of colistin antibacterial activity in the presence of fixed concentration of rifampicin (0.5 mg/L) was observed as a 4–16-fold MIC decrease for <em>K. pneumoniae</em> and <em>A. baumannii</em>. In the presence of fixed concentrations of azithromycin (2 mg/L) or clarithromycin (1 mg/L), the colistin MICs decreased 64–512 times for <em>K. pneumoniae</em>, 4–32 times for <em>A. baumannii</em>, 16–64 times for <em>P. aeruginosa</em>. Two- or more-fold reduction of MIC of colistin in the presence of 1 mg/L clarithromycin was observed for 85.2% of <em>K. pneumoniae</em>, 86.3% of <em>A. baumannii</em> and 60.2% of <em>P. aeruginosa</em> strains. In the presence of 1 mg/L clarithromycin and 8 mg/L meropenem, the potentiation effect was enhanced and was observed for an even larger percent of isolates: 96.1% <em>K. pneumoniae</em>, 98.0% <em>A. baumannii</em> and 61.3% <em>P. aeruginosa</em>. Colistin-based combinations with clarithromycin-meropenem and clarithromycin-doripenem were bactericidal against most isolates of <em>A. baumannii</em> and <em>P. aeruginosa</em> (91.4–100%), and against colistin-sensitive <em>K. pneumoniae</em> (95.3%) and colistin-resistant <em>K. pneumoniae</em> (79.1%).</p> <h3 id="conclusions">Conclusions.</h3> <p>The ability of macrolides to significantly potentiate the colistin antimicrobial activity against both colistin-sensitive and colistin-resistant strains of <em>K. pneumoniae</em>, <em>A. baumannii</em> and <em>P. aeruginosa</em> was shown. This potentiation effect was enhanced in the presence of carbapenems. The most potent bactericidal activity was revealed with dual and triple combinations of colistin-clarithromycin and colistinclarithromycin-carbapenems.</p> http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p119/ Thu, 28 May 2020 11:03:11 +0000 http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p119/ <h3 id="objective">Objective.</h3> <p>To assess efficacy and safety of 14-day triple nifuratel-based therapy compared to 14-day standard triple therapy in adult patients with symptomatic <em>H. pylori</em> infection.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 70 patients with dyspepsia and microbiologically confirmed <em>H. pylori</em> infection were enrolled into the open-label, randomized, comparative clinical trial. The study group (n = 35) received a 14-day triple nifuratel-based therapy: esomeprazole (20 mg BID), nifuratel (400 mg BID) and amoxicillin (1000 mg BID). The comparator group (n = 35) received 14-day conventional clarithromycinbased triple therapy: esomeprazole (20 mg BID), clarithromycin (500 mg BID) and amoxicillin (1000 mg BID). Eradication of <em>H. pylori</em> was assessed using stool antigen test.</p> <h3 id="results">Results.</h3> <p>Eradication rates for 14-day nifuratel-based triple therapy and 14-day clarithromycin-based triple therapy in the intent-to-treat (ITT) population were 82.9% and 74.3% (p = 0.561), respectively. In the per-protocol (PP) population, eradication rates were 90.6% and 89.7% (p = 1.00), respectively. Adverse events were reported in 17.1% of patients in the study group and 34.3% of patients in the comparator group (p &gt; 0.05).</p> <h3 id="conclusions">Conclusions.</h3> <p>The 14-day triple nifuratel-based therapy has demonstrated a high <em>H. pylori</em> eradication rate (above 90%). Nifuratel triple therapy may be considered as an alternative to clarithromycin-based triple therapy for patients with a history of the prior macrolide exposure or macrolide intolerance.</p> http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p092/ Thu, 28 May 2020 10:59:29 +0000 http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p092/ <h3 id="objective">Objective.</h3> <p>To determine antigenic and genetic characteristics of <em>Neisseria meningitidis</em> isolated from the patients with invasive meningococcal infections in Smolensk region in comparison with those circulating in other regions.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 14 cerebrospinal fluid samples obtained in 2016–2019 and containing <em>N. meningitidis</em> DNA were tested using AmpliSens® Nm-ABCW kit, multilocus sequence typing and antigenic finetyping of outer membrane proteins. The results were analyzed by the BURST algorithm and other functionalities available at PubMLST.org (Jolley K. et al. 2018).</p> <h3 id="results">Results.</h3> <p>The variable region alleles, sequence types and clonal complexes were determined for the tested isolates. The genotyping results were published in the PubMLST database (<a href="https://pubmlst.org/neisseria/" target="_blank">https://pubmlst.org/neisseria/</a>). Most of <em>N. meningitidis</em> serogroup B isolates (n = 6) belonged to sequence types which have not been described previously: ST-14705, ST-14710, ST-14711, ST-14713 and ST-14717. Sequence types of serogroup C isolates (n = 7) were usual for strains circulating in other Russian regions (4 of 7 belonged to ST-8416). The only serogroup Y isolate belonged to ST-11585.</p> <h3 id="conclusions">Conclusions.</h3> <p>Most studied <em>N. meningitidis</em> sequence types belonged to clonal complexes designated in PubMLST database and groups of isolates, determined by the BURST algorithm, which were usual for Russian regions. The antigenic and genetic characteristics suggest no circulation of epidemiologically significant <em>N. meningitidis</em> strains or hypervirulent strains on the observed territory.</p> http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p088/ Thu, 28 May 2020 10:58:08 +0000 http://cmac-journal.ru/en/publication/2020/2/cmac-2020-t22-n2-p088/ <h3 id="objective">Objective.</h3> <p>To assess efficacy and safety of methylprednisolone pulse therapy in patients with COVID-19.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective analysis of 57 patients with moderate and severe novel coronavirus infection (COVID-19) receiving methylprednisolone pulse therapy (500 mg/day IV for 2–3 consecutive days) was performed. Pre- and post-therapy examination of the patients included clinical (severity and duration of fever, gas exchange parameters), imaging (computed tomography) and laboratory tests (including C-reactive protein, procalcitonin, D-dimer).</p> <h3 id="results">Results.</h3> <p>Methylprednisolone pulse therapy resulted in improved gas exchange (the mean duration of SpO2 recovery was 3.9 ± 0.25 days), body temperature normalization (the mean time to defervescence was 2.1 ± 0.2 days), significant decrease in inflammatory marker levels (CRP, D-dimer). No patients required an enhancement of respiratory support (transfer to ICU). Methylprednisolone pulse therapy was well-tolerated and did not cause bacterial complications.</p> <h3 id="conclusions">Conclusions.</h3> <p>Methylprednisolone pulse therapy in patients with COVID-19 was shown to decrease activity of systemic inflammatory response, severity of coagulation disorders and contribute to recovery of gas exchange lung function. Given the high efficacy and low cost of methylprednisolone pulse therapy, it could be one of the promising approaches to the management of patients with moderate and severe COVID-19. Further studies are needed to determine prognostic criteria of progression and optimal time for initiation of corticosteroid therapy.</p> http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p071/ Sun, 15 Mar 2020 11:37:34 +0000 http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p071/ <h3 id="objective">Objective.</h3> <p>To determine the efficacy and safety of direct-acting antiviral agents (DAA) in patients with chronic HCV infection and UGT1A1*28 polymorphism.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>An open-label, non-randomized, observational study to assess efficacy and safety of DAA in patients (n = 143) with chronic hepatitis C (CHC) and liver cirrhosis and UGT1A1*28 polymorphism was performed. A total of 139 patients with chronic HCV infection were included in the efficacy analysis (absence of HCV RNA in blood by PCR) by the rate of sustained virologic response at week 12 (SVR12).</p> <h3 id="results">Results.</h3> <p>The SVR12 rate in patients with CHC and HCV-CP was 92.5% and 87.9%, respectively (p = 0.508), regardless of the presence of UGT1A1*28 polymorphism. The SVR12 rate in patients with chronic HCV infection and (TA)7/(TA)7 was 84.8%, with (TA)6/(TA)7 – 92.2% compared with (TA)6/ (TA)6 – 90,5% (p = 0.518). The rate of SVR12 in patients with CHC and (TA)7/(TA)7 or (TA)6/(TA)7 was 80% and 95%, respectively, with (TA)6/(TA)6 – 95.2%. The rate of SVR12 in patients with liver cirrhosis and (TA)7/(TA)7 or (TA)6/(TA)7 was 92.3% and 87.5%, respectively, with (TA)6/(TA)6 – 85.7%. The rate of SVR12 in patients with 12- and 24-week treatment duration was 88.2% and 96.6%, respectively (p = 0.30). As many as 96.2% of patients with the previous treatment with interferon and ribavirin had SVR12 compared to 88.5% of patients who have not previously taken antiviral drugs (p = 0.486). Grade 1 adverse events (AE) occurred in 24% of patients with chronic HCV infection treated with DAA; two patients developed Grade 4 AE.</p> <h3 id="conclusions">Conclusions.</h3> <p>The treatment with DAA was shown to be effective and safe in patients with chronic HCV infection and UGT1A1*28 polymorphism.</p> http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p067/ Sun, 15 Mar 2020 11:33:33 +0000 http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p067/ <h3 id="objective">Objective.</h3> <p>To evaluate effect of «Haemoblock»TM preparation on <em>in vitro</em> bacterial colonization.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Activity of «Haemoblock»ТМ product on the growth and colonization of <em>S. aureus</em> АТСС 25923, <em>S. epidermidis</em> ATCC 28922, <em>E. coli</em> АТСС 25922, <em>P. aeruginosa</em> АТСС 27853 cells in the suspension and on the surface of monofilament macroporous polyester mesh was evaluated.</p> <h3 id="results">Results.</h3> <p>This product at concentration of 0.062% and above inhibited bacterial growth and reduced biofilm mass and bacterial cell viability. In addition, the short-term exposure of the mesh implant to the tested product resulted in inhibition of the abiotic surface contamination.</p> <h3 id="conclusions">Conclusions.</h3> <p>«Haemoblock»TM product allows not only to ensure hemostasis in open and laparoscopic surgery, but also to reduce the bacterial cell count in the surrounding tissues in the intra- and post-operative periods.</p> http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p060/ Sun, 15 Mar 2020 11:31:39 +0000 http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p060/ <h3 id="objective">Objective.</h3> <p>The purpose of this study was to study the frequency of achievement of target values of vancomycin residual concentration (RC) and to identify the factors influencing this indicator.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective observational study of vancomycin RC was performed in 471 patients who received vancomycin infusions in the department of purulent surgery of the RSRI of TO named after R.R. Vreden about capillary instillation after major orthopedic operations over the period from 01.01.2014 to 05.31.2016.</p> <h3 id="results">Results.</h3> <p>The target RC values on the third day of vancomycin administration reached 12.1% of patients (76.2% below target RC), after correction of the dosing regimen, the target RC was achieved in 20.3% of patients (56.9% below target RC). Multivariate analysis revealed a connection between RC and age (an increase in RC in age patients) and sex (a higher RC in women). In most cases, the prescribed doses of vancomycin corresponded to the recommended, however, the target RC levels of vancomycin were achieved only in a small proportion of patients.</p> <h3 id="conclusions">Conclusions.</h3> <p>At the same time, the lowest frequency of reaching target concentrations was observed in young patients. The study proposed a multifactor model of vancomycin RC, on the basis of which it is possible to carry out the best correction of dosing taking into account the factors of age and sex.</p> http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p053/ Sun, 15 Mar 2020 11:29:56 +0000 http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p053/ <h3 id="objective">Objective.</h3> <p>To develop an approach to comprehensive analysis and presentation of data on antibiotic resistance of zoonotic bacteria to minimize antibiotic resistance in the medical and veterinary fields using the AMRcloud platform.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Isolates of <em>E. coli</em>, <em>Salmonella</em> spp., <em>Enterococcus</em> spp. and <em>Campylobacter</em> spp. were taken from farm animals, food and feed. AST was performed by broth microdilution method. Genes of resistance were detected by whole-genome sequencing or PCR. Data analysis and visualization was made using AMRcloud online platform.</p> <h3 id="results">Results.</h3> <p>During veterinary monitoring from 2017 to 2019 resistance to ~50 antimicrobial agents was determined of totally 854 isolates of 11 bacterial species taken from more than 20 types of samples from 6 animal species in 22 regions of Russia. Genes of resistance were determined for 126 isolates. Data is presented in open access VGNKI project on AMRcloud online platform: <a href="https://amrcloud.net/en/project/vgnki/" target="_blank">https://amrcloud.net/en/project/vgnki/</a>.</p> <h3 id="conclusions">Conclusions.</h3> <p>The use of AMRcloud allowed us to complete all tasks of the project in short time. The platform takes methodology of data analysis to a fundamentally new level comparing to traditional tools and increases the efficiency of monitoring for controlling spread of AMR.</p> http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p047/ Sun, 15 Mar 2020 11:28:01 +0000 http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p047/ <h3 id="objective">Objective.</h3> <p>To evaluate the resistance rate and production of carbapenemases in <em>Klebsiella pneumoniae</em> with phenotypic resistance to carbapenems isolated from patients with orthopedic infection.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>The materials for the study were tissue samples, aspirates and removed orthopedic devices of patients with orthopedic infection at the Vreden Russian Research Institute of Traumatology and Orthopedics, between 2017 and 2019. <em>K. pneumoniae</em> strains were identified in Microlatest by iEMS ReaderMF. These strains were tested for susceptibility to 15 antimicrobial agents by disk diffusion methods, as described by the EUCAST. The carbapenemase genes were investigated by RT-PCR.</p> <h3 id="results">Results.</h3> <p>Of 858 isolated cultures, 6.8% were resistant to carbapenems. Molecular genetic analysis showed that 43.1% of the cultures had blaNDM gene and 24.1% blaOXA-48. All isolates of <em>K. pneumoniae</em> were characterized by resistance to cefotaxime, moxifloxacin and ciprofloxacin. OXA-48-strains were MDR in 50.0% of cases, XDR in 42.9%, PDR in 7.1%. Strains with NDM-carbapenemases were XDR in 68.0% and PDR in 32.0% of cases. The most effective antibiotic was fosfomycin. Thus, 66.7% of NDM-isolates demonstrated sensitivity to fosfomycin. One isolate was PDR with both NDM and OXA-48.</p> <h3 id="conclusions">Conclusions.</h3> <p>Over the period of three years, carbapenemase-producing <em>K. pneumoniae</em> were isolated in the orthopedic hospital. These isolates were not only resistant to carbapenems, but also to a number of other antimicrobial agents. Isolates differed in resistance phenotypes depending on the presence of carbapenemases group, while strains with gene blaNDM were more resistant than those with blaOXA-48.</p> http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p040/ Sun, 15 Mar 2020 11:26:11 +0000 http://cmac-journal.ru/en/publication/2020/1/cmac-2020-t22-n1-p040/ <h3 id="objective">Objective.</h3> <p>To evaluate antimicrobial resistance patterns of clinical <em>Streptococcus pyogenes</em> isolates from different regions of Russia during 2014–2017.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 792 clinical <em>S. pyogenes</em> isolates from 14 Russian cities were included in the study. Susceptibility testing was performed using reference broth microdilution method (ISO 207761:2006). Susceptibility testing results were interpreted using EUCAST v.10.0 breakpoints.</p> <h3 id="results">Results.</h3> <p>Penicillin G was active against all tested isolates with the MIC50–90 values of 0.016 mg/l and the highest MIC value of 0.25 mg/l. No resistance to linezolid, tedizolid and vancomycin were observed. Respiratory fluoroquinolones, moxifloxacin and levofloxacin, showed a high activity with the only 0.3% and 0.8% of resistant isolates, respectively. Almost all isolates (99.9%) were susceptible to trimethoprim/ sulfamethoxazole. The resistance rates to 14- and 15-membered macrolides varied from 12.1% to 17.2%. The only 2.4% of isolates were resistant to clindamycin. Resistance to chloramphenicol was 6.1%, to tetracycline – 17.2%.</p> <h3 id="conclusions">Conclusions.</h3> <p>The comparison of this study results with the previously published Russian data on antimicrobial resistance of <em>S. pyogenes</em> shows there were no significant changes in the susceptibility of this pathogen over the past two decades, with the exception of macrolides. The growing resistance to 14and 15-membered macrolides raises a question on the further use of this antibiotic class for the empiric treatment of streptococcal infections in Russia.</p> http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p359/ Wed, 04 Mar 2020 11:00:33 +0000 http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p359/ <h3 id="objective">Objective.</h3> <p>To determine the effect of the tinctorial properties of microorganism on the nutritional status and the early outcome in patients with systemic inflammatory response syndrome (SIRS) of bacterial origin.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A retrospective statistical analysis of case histories of 137 patients with signs and symptoms of SIRS and bacterial infections (caused by a single pathogen) was performed. The following clinical and laboratory parameters of protein-energy undernutrition (PEU) were determined and assessed: body mass index, body weight deficit, total protein, serum albumin, absolute peripheral blood lymphocyte count. Basic metabolic rate indicators (daily energy demand, macronutrient demand) were calculated by indirect calorimetry. The severity of patients at hospital admission is assessed using the SOFA.</p> <h3 id="results">Results.</h3> <p>The statistically significant effect of the tinctorial properties of microorganism on the nutritional status and the early outcome in patients with SIRS of bacterial origin was confirmed.</p> <h3 id="conclusions">Conclusions.</h3> <p>The type of microorganism determined by tinctorial properties has a different effect on patient’s metabolic status. Patients with Gram-negative infections have an increased protein and protein caloric intake. Patients with Gram-positive infections have an increased energy requirements and macronutrient intake. The indicators of the baseline PEU in patients with SIRS of bacterial origin have a significant effect on the disease outcome. The study results stress the importance of nutritional therapy directed to adjustment of daily caloric intake and the percentage of protein calories in patients with systemic bacterial inflammation.</p> http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p352/ Wed, 04 Mar 2020 11:00:31 +0000 http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p352/ <h3 id="objective">Objective.</h3> <p>To identify mutations in UL97 gene associated with antiviral drug resistance in recipients of allogeneic hematopoietic stem cells transplants (allo-HSCT).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 9 HCMV DNA samples were studied. These samples were received from the blood of 8 allo-HSCT recipients who were infected with HCMV and undergoing treatment at NMRC of Hematology (Russia) over the period of 2016 to 2017. Sanger sequencing was used to find mutations. The sequenced part of the virus DNA was analyzed using nucleotide BLAST and Genome compiler. Mutations were identified using MRA program which compared the obtained nucleotide sequence with the reference sequence of UL97 gene from Merlin strain.</p> <h3 id="results">Results.</h3> <p>Rate of detection of viruses with mutations that may lead to drug resistance is relatively high – 3 of 8 patients. The following mutations were identified: C592G, C607F and C603W. The obtained data shows that the presence and characteristics of mutations affect the viral load and the time when HCMV DNA is identified in blood.</p> <h3 id="conclusions">Conclusions.</h3> <p>Obtained data show that presence of mutations impacts the course infection, leading to higher viral load and longer persistence of viral DNA in blood samples. Identified mutations had different resistance factor, which also impacted on the pattern of infection.</p> http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p340/ Wed, 04 Mar 2020 11:00:30 +0000 http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p340/ <h3 id="objective">Objective.</h3> <p>To present the data on the main mechanism of molecular variation in <em>P. aeruginosa</em> causing chronic lung infection in patients with cystic fibrosis.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 1800 throat swabs and sputum samples from cystic fibrosis patients were included in the study over the 10-year period. <em>P. aeruginosa</em> isolates were primarily identified by the biochemical method using the API 20NE test strips (bioMerieux, France). Antimicrobial susceptibility testing was performed by disc diffusion method. Genotyping was conducted by RAPD-PCR and MLST. Whole genome sequencing of three typical <em>P. aeruginosa</em> isolates was performed on an Ion PGM Torrent platform with Ion Sequencing Kit and 316v1 chips (Life Technologies Thermo Fisher, US) according to the manufacturer’s protocol. The RAST web application was used for initial annotation.</p> <h3 id="results">Results.</h3> <p>There were three main variants of the pathogen variability found: population heterogeneity, pathogen microevolution, and replacement by another genotype of the same species. The variation of the pathogen’s genome is due to the acquisition of mobile genetic elements (plasmids), mutations in the chromosomal genes responsible for antibiotic resistance, bacterial viability and survival during persistence in a host, and changes in the prophage regions of the pathogen.</p> <h3 id="conclusions">Conclusions.</h3> <p>Epidemiological significance of the molecular mechanisms of pathogen variation is primarily due to the ability of strains to form epidemiologically significant clone. This requires control measures aimed to limit emergence and distribution of such clones to be developed.</p> http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p330/ Wed, 04 Mar 2020 11:00:29 +0000 http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p330/ <h3 id="objective">Objective.</h3> <p>In this study, we examined the prevalence of macrolide-resistant <em>M. genitalium</em> in two Russian cities, Smolensk and Tula, between 2013 and 2017.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>DNA’s samples were isolated from urethral and cervicovaginal swabs using primary screening and tested for macrolide resistance-associated mutations by real-time PCR. This technology makes it possible to identify any nucleotide substitutions in the 23S rRNA <em>M. genitalium</em> gene at positions 2058, 2059, 2611 <em>M. genitalium</em> by melting curve analysis after the amplification.</p> <h3 id="results">Results.</h3> <p>According to the study in two cities (Smolensk and Tula) macrolide resistance-associated mutations were found in 3, 65% of isolates (²¹&frasl;₅₇₄). The A2058G transition 23S rRNA MGE was the most common mutation that is associated with macrolide resistance: ⁵&frasl;₁₂ (41.6%) – Smolensk, ⁸&frasl;₉ (88.8%) – Tula. Rare substitutions have been reported at position A2058T 23S rRNA MGE and at position C2611T23S rRNA MGE. All received data is published at the AntiMicrobial Resistance Map (AMRmap) (<a href="http://AMRmap.com" target="_blank">http://AMRmap.com</a>).</p> <h3 id="conclusions">Conclusions.</h3> <p>According to our study, the frequency of macrolide-resistance mutations in <em>M. genitalium</em> was not more than 4% in two cities of Central Russia during 2013–2017. Despite the relatively low rates of resistance of <em>M. genitalium</em> to macrolides in Smolensk and Tula, our data emphasize the need for epidemiological surveillance of resistance in this pathogen.</p> http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p317/ Wed, 04 Mar 2020 11:00:27 +0000 http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p317/ <h3 id="objective">Objective.</h3> <p>To evaluate antimicrobial resistance patterns of clinical <em>Haemophilus influenzae</em> isolates from different regions of Russia during 2014–2017.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We included in the study 185 clinical <em>H. influenzae</em> isolates from 13 Russian cities. Susceptibility testing was performed by reference broth microdilution method (ISO 207761:2006). Susceptibility testing results were interpreted using EUCAST v. 10.0 breakpoints.</p> <h3 id="results">Results.</h3> <p><em>H. influenzae</em> isolates were highly susceptible to all (96.8%-100%) β-lactams tested (amoxicillin/ clavulanate, cefixime, ceftaroline, ceftibuten, cefditoren, ertapenem) with the exception of ampicillin (15.1% isolates were resistant). Fluoroquinolones, – ciprofloxacin, levofloxacin, moxifloxacin were active against 95.7%, 94.6% and 97.9% of isolates, respectively. Chloramphenicol was active against 97.9% of isolates, tetracycline – against 98.4% of isolates. Activity of trimethoprim/sulfamethoxazole was low (69.2% of susceptible isolates).</p> <h3 id="conclusions">Conclusions.</h3> <p>In general, we can state the favorable situation with the susceptibility of <em>H. influenzae</em> to antimicrobials in Russia. However, the increasing of resistance to aminopenicillins and emerging of quinolone-resistant strains could become a problem in the future. Study Results are deposited at on-line resource AMRmap (<a href="http://AMRmap.ru" target="_blank">http://AMRmap.ru</a>).</p> http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p275/ Wed, 04 Mar 2020 11:00:24 +0000 http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p275/ <h3 id="objective">Objective.</h3> <p>To estimate the prevalence of <em>S. pneumoniae</em> serotypes in adults aged of 18 years and older, including healthy carriers and patients with acute otitis media (AOM), community-acquired pneumonia (CAP) and invasive pneumococcal infection (IPI).</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 230 isolates of <em>S. pneumoniae</em> from 10 centers were included in the study from 01.06.2019 to 01.10.2019. Re-identification and typing using real-time PCR with 22 primer pairs were performed in the central laboratory (Institute of Antimicrobial Chemotherapy, Russia).</p> <h3 id="results">Results.</h3> <p>In healthy nasopharyngeal carriers (n = 31), the following serotypes of <em>S. pneumoniae</em> were detected: 19F (29.0%), 6А/В (22.6%), 3 (16.1%), 11A/D and 23F (9.7% each), 23A (6.4%), 14 and 15A/F (3.2% each); PCV-13 and PPV-23 covered 80.6% and 90.3% of those serotypes, respectively. In patients with AOM (n = 18), serotypes were: 3 (16.7%), 11A/D and 6A/B (11.1%, each), 16, 19А, 19F, 23F, 7A/F (5.55%, each); PCV-13 and PPV-23 covered 50% and 61.1% of those serotypes, respectively. Among 166 isolates from patients with CAP, the following serotypes were detected: 3 (12.0%), 19F and 6A/B (10.2%, each), 14 and 11A/D (5.4% each), 15A/F and 23A (4.8% each), 9N/L (4.2%), 18 and 22A/F (2.4% each), 19A and 23F (1.8% each), 16, 9V/A (1.2% each), 4 and 33A/33F/37 (0.6% each), non-vaccine serotypes (30.3%); PCV-13 and PPV-23 covered 45.6% and 57.0% of those serotypes, respectively. Isolates from patients with IPI (n=15) belonged to the following serotypes: 3 (26.7%), 12F, 23F and 9N/L (13.3% each), serotypes 4 and 15A/F (6.7%), non-vaccine serotype – 1 isolate (6.7%); PCV-13 and PPV-23 covered 46.7% and 73.3% of those serotypes, respectively.</p> <h3 id="conclusions">Conclusions.</h3> <p>The majority of <em>S. pneumoniae</em> serotypes in adult population in Russia are included in PPV-23, but not in PCV-13 (primarily due to serotype 11A/D). There was a high PCV-13 and PPV-23 coverage of serotypes from healthy nasopharyngeal carriers. PPV-23 covered more than 60% of clinical isolates, whereas PCV-13 covered less than 60% (AOM – 50.0%, CAP – 45.6%, IPI – 46.7%), thus indicating a potentially lower efficacy of PCV-13 in adult population.</p> http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p261/ Wed, 04 Mar 2020 11:00:23 +0000 http://cmac-journal.ru/en/publication/2019/4/cmac-2019-t21-n4-p261/ <h3 id="objective">Objective.</h3> <p>To perform a comparative analysis of clinical and food isolates of <em>Listeria monocytogenes</em> collected in the European part of Russia in 2018–2019.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We used multilocus sequencing (MLST), supplemented by virulence loci, including fragments of internalin genes (MvLST, Multi-virulent-locus sequence typing), followed by phylogenetic analysis.</p> <h3 id="results">Results.</h3> <p>The main diagnoses for clinical isolates were prenatal and neonatal listeriosis and meningitis. Clinical isolates predominantly belonged to phylogenetic line II with the predominance of ST7, which was also the most abundant in food isolates. The second most common occurrence in food isolates was ST121, widely distributed in Europe. Isolates of phylogenetic line I in the group of clinical cultures in three cases were represented by ST6, detected during outbreaks of listeriosis in Europe 2015–2018 and South Africa in 2017–2018. Only in one isolate from food belonged to the phylogenetic lineage I. In general, the diversity of food isolate genotypes was significantly higher than clinical isolates. The analysis of virulence loci revealed a new internalin A allele and a new internalin genes profile (IP) in isolate ST7 from food.</p> <h3 id="conclusions">Conclusions.</h3> <p><em>L. monocytogenes</em> of the most common ST7 is autochthonous in Russia; cases of listeriosis caused by the ST6 bacterium are most likely imported. Based on the analysis of the diversity of ST and IP of <em>L. monocytogenes</em> identified in Russia, a rapid diagnosis scheme for epidemiological investigation is proposed.</p> http://cmac-journal.ru/en/publication/2019/3/cmac-2019-t21-n3-p238/ Thu, 05 Dec 2019 00:06:49 +0000 http://cmac-journal.ru/en/publication/2019/3/cmac-2019-t21-n3-p238/ <h3 id="objective">Objective.</h3> <p>To estimate composite indicators of systemic antibiotic consumption in the hospital segment of Saint-Petersburg in 2014–2018.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Information on the volume and structure of AMP consumption in the hospital segment of St. Petersburg in 2014–2018 was obtained from AlfaRm Databases. The amount of purchased AMP was recalculated in the number of average daily maintenance doses (Defined Daily Dose, DDDs), as well as DDDs per 100 bed-days (DDDh) for each international nonproprietary name of AMP. Data on the bed-days spent in the period 2014–2018, as well as the epidemiological situation in hospitals of St. Petersburg in the period 2016–2018 were obtained from the databases of St. Petersburg state medical institution MIAC. Based on data on AMP consumption and the epidemiological situation in hospitals in St. Petersburg, the indicator of a comprehensive assessment of AMP consumption – the drug resistance index (DRI) was calculated.</p> <h3 id="results">Results.</h3> <p>During the study, there was a decrease in the absolute consumption of AMP from 17.6 to 9.2 million DDDs, with a decrease in DDDh from 125 to 66, accompanied by a decrease in the total cost of purchasing AMP from 74 to 67 million rubles per year. Fluoroquinolones, other AMP and cephalosporins remained the main classes of AMP for systemic use throughout the observation period. At the same time, the relative amounts of resistant strains of the ESKAPE group of bacteria, as well as DRI, remained virtually unchanged.</p> <h3 id="conclusions">Conclusions.</h3> <p>Pharmacoepidemiological monitoring data provide a picture of current trends in the use of AMP and can serve as a guide for the treatment of patients, identifying risk groups, informing policy makers and used to assess the effectiveness of measures taken.</p> http://cmac-journal.ru/en/publication/2019/3/cmac-2019-t21-n3-p230/ Thu, 05 Dec 2019 00:05:49 +0000 http://cmac-journal.ru/en/publication/2019/3/cmac-2019-t21-n3-p230/ <h3 id="objective">Objective.</h3> <p>To evaluate antimicrobial resistance patterns of clinical <em>Streptococcus pneumoniae</em> isolates from different regions of Russia during 2014–2017.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>We included in the study 519 clinical <em>S. pneumoniae</em> isolates from 18 Russian cities. Susceptibility testing was performed by reference broth microdilution method (ISO 20776-1:2006). Susceptibility testing results were interpreted according to EUCAST v.9.0 breakpoints.</p> <h3 id="results">Results.</h3> <p>Using EUCAST non-meningeal interpretation criteria, 65.1% of isolates tested were susceptible (S) to penicillin; in addition 28.9% were in the category “susceptible, increased exposure” (I). S and I to ampicillin were 74.8% and 11.0% of isolates; to ceftriaxone – 79.0% and 15.6%, respectively. S to ertapenem and ceftaroline were 93.6% and 98.1% of isolates. Almost all isolates (99.6%) were S to respiratory fluoroquinolones (levofloxacin and moxifloxacin) and chloramphenicol (98.3%). All isolates were S to linezolid and vancomycin. Different 14-15-member macrolides were active against 67.8%–72.8% of isolates, activity of clindamycin was significantly higher (85.9%). Susceptibility rates to tetracycline and trimethoprim/sulfamethoxazole were 66.1% and 59.0%, respectively.</p> <h3 id="conclusions">Conclusions.</h3> <p>There was a trend to decrease in susceptibility of <em>S. pneumoniae</em> in Russia to conventional β-lactams, macrolides and lincosamides. The most <em>in vitro</em> active antimicrobials are respiratory fluoroquinolones, linezolid, vancomycin, ceftaroline and chloramphenicol.</p> http://cmac-journal.ru/en/publication/2019/3/cmac-2019-t21-n3-p207/ Thu, 05 Dec 2019 00:01:49 +0000 http://cmac-journal.ru/en/publication/2019/3/cmac-2019-t21-n3-p207/ <h3 id="objective">Objective.</h3> <p>To evaluate <em>Staphylococcus</em> species diversity and methicillin resistance in nosocomial infections.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>Staphylococci isolated from blood, bronchoalveolar lavage fluid, cerebrospinal fluid, post-operative wound exudates, urine and other samples were identified to species level with MALDITOF mass-spectrometry. Methicillin resistance was evaluated according to EUCAST guidelines.</p> <h3 id="results">Results.</h3> <p>A total of 3239 consecutive Staphylococcus strains isolated in a tertiary-care medical centre, accumulating patients from all Russian regions were identified in 2016–2017 as 1460 (45.1%) of <em>S. aureus</em> strains and 1779 (54.9%) of coagulase-negative staphylococci, presenting 12 species (<em>S. epidermidis, S. haemolyticus, S. hominis, S capitis, S. warneri, S. lugdunensis, S. simulans, S. caprae, S. saprophyticus, S. cohnii, S. sciuri, S. auricularis</em>). <em>S. epidermidis</em> was isolated in 1164 (35.9%) samples, <em>S. haemolyticus</em> – in 305 (9.4%), <em>S. hominis</em> in 215 (6.6%), <em>S. capitis</em> in 46 (1.4%) cases. Other <em>Staphylococcus</em> spp. were isolated from less than 1% of samples. Methicillin-resistant were 1628 (50.3%) <em>Staphylococcus</em> strains, including 202 (13.8%) <em>S. aureus</em> isolates, 933 (80.2%) – <em>S. epidermidis</em>, 283 (92.5%) – <em>S. haemolyticus</em>, 182 (84.7%) – <em>S. hominis</em>, 8 (17.4%) – <em>S. capitis</em>.</p> <h3 id="conclusions">Conclusions.</h3> <p>Significant species diversity in staphylococci, isolated from patients samples in a multidisciplinary medical center in Saint-Petersburg in 2016–2017, was revealed. <em>S. aureus</em> prevailed in nosocomial infections of different localizations, accounting for more than a half of isolated <em>Staphylococcus</em> spp. Among coagulase-negative staphylococci ¹&frasl;₃ of isolated strains were <em>S. epidermidis</em> (the most common species in this group). Methicillin resistance was found in a half of <em>Staphylococcus</em> spp. strains. The level of methicillin-resistance in <em>S. aureus</em> was 13.8%, with decrease from 15.6% in 2016 to 12.3% in 2017. <em>S. haemolyticus, S. hominis</em> and <em>S. epidermidis</em> showed the highest level of methicillin resistance (more than 80%). All of the <em>S. auricularis, S. cohnii, S. caprae, S. lugdunensis</em> and <em>S. sciuri</em> isolates were methicillin-susceptible.</p> http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p187/ Thu, 10 Oct 2019 00:11:00 +0000 http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p187/ <h3 id="objective">Objective.</h3> <p>To study antimicrobial susceptibility of <em>Streptococcus pneumoniae</em> clinical isolates obtained from the patients with community-acquired pneumonia in the Central Kazakhstan.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 186 clinical strains of <em>S. pneumoniae</em> were obtained from the patients with respiratory tract infections in the Central Kazakhstan over the period of 2012–2017. Antimicrobial susceptibility was determined by disk-diffusion method. The isolation and identification of pathogens was performed by routine methods. Antimicrobial (oxacillin, vancomycin, clindamycin, azithromycin, chloramphenicol, tetracycline, rifampin, levofloxacin, linezolid, trimethoprim/sulfamethoxazole) susceptibility testing was performed and interpreted according to CLSI criteria (M100-24).</p> <h3 id="results">Results.</h3> <p>The resistance rates were the following: oxacillin – 4.2%, azithromycin – 12.4%, tetracycline – 71.1%, chloramphenicol – 7.8%, trimethoprim/sulfamethoxazole – 57.1%, rifampin – 5.6% and levofloxacin – 3.4%. There were no <em>S. pneumoniae</em> isolates resistant to linezolid or vancomycin.</p> <h3 id="conclusions">Conclusions.</h3> <p>The amoxicillin is recommended as a drug of choice for antimicrobial therapy of pneumococcal respiratory tract infections.</p> http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p181/ Thu, 10 Oct 2019 00:10:00 +0000 http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p181/ http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p171/ Thu, 10 Oct 2019 00:09:00 +0000 http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p171/ <h3 id="objective">Objective.</h3> <p>Objectives. To assess the rates of antibiotic resistance and production of acquired carbapenemases in nosocomial strains of <em>Acinetobacter</em> spp., and to determine the genotypes and prevalence of “international high-risk clones” among nosocomial strains of <em>Acinetobacter baumannii</em> isolated in various regions of Russia within the “MARATHON 2015–2016” study.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 1005 non-duplicate nosocomial isolates of <em>Acinetobacter</em> spp., including 975 isolates of <em>A. baumannii</em>, collected in 44 hospitals from 25 cities in Russia in 2015– 2016 were studied. Species identification of isolates was performed by means of MALDI-TOF massspectrometry. Antimicrobial susceptibility was determined using broth microdilution method according to ISO 20776-1:2006 and interpreted using EUCAST MIC clinical breakpoints v.9.0. The presence of acquired carbapenemase genes of OXA-23, OXA-²⁴&frasl;₄₀, OXA-58, VIM, IMP, NDM, GES-2 and GES-5 groups was determined using real-time PCR. Genotyping of <em>A. baumannii</em> isolates was performed by analysis of selected single nucleotide polymorphisms in 10 chromosomal loci used for multi-locus sequence tying (MLST) of this species.</p> <h3 id="results">Results.</h3> <p><em>Acinetobacter</em> spp. and <em>A. baumannii</em> comprised of 17.4% and 16.8% of all bacterial pathogens isolated within the “MARATHON 2015–2016” study. Resistance rates to carbapenems (imipenem and meropenem) were 77.4% and 77.1% of <em>A. baumannii</em> isolates, respectively. In 76.2% of <em>A. baumannii</em> isolates, the genes of acquired carbapenemases of molecular class D were detected, which belonged to the following groups: OXA-²⁴&frasl;₄₀ (57.5%), OXA-23 (18.4%) and OXA-58 (0.1%). Two isolates (0.2%) carried the genes of OXA-²⁴&frasl;₄₀- and OXA-23-like carbapenemases simultaneously. Most carbapenemaseproducing isolates belonged to the «international high-risk clones»: CC92/208OXF/CC2PAS (60.3%), CC944OXF/CC78PAS (25.4%) and CC109/231OXF/CC1PAS (11.6%). The vast majority of <em>A. baumannii</em> isolates exhibited resistance to ciprofloxacin (99.0%), amikacin (89.2%) and gentamicin (77.4%). The prevalence of resistance to tobramycin and trimethoprim/sulfamethoxazole was variable among strains of different genotypes. Colistin was the most active agent <em>in vitro</em> (0.9% of resistant isolates). Isolates of other <em>Acinetobacter</em> species were more susceptible to most antibiotics. However, two isolates of <em>Acinetobacter ursingii</em> and <em>Acinetobacter baylyi</em> carried the genes of NDM metallo-beta-lactamases.</p> <h3 id="conclusions">Conclusions.</h3> <p>The results of this study indicate a very high prevalence of resistance to most antibiotics, including carbapenems, in nosocomial strains of <em>Acinetobacter</em> spp. This makes the selection of empiric antibiotic treatment extremely difficult and urges the need for regular local surveillance of resistance in every hospital.</p> http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p160/ Thu, 10 Oct 2019 00:08:00 +0000 http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p160/ <h3 id="objective">Objective.</h3> <p>Objectives. To assess the rates of antibiotic resistance, production of acquired carbapenemases, genotypes and prevalence of «international high-risk clones» among nosocomial strains of <em>Pseudomonas aeruginosa</em> isolated in various regions of Russia within the «MARATHON 2015–2016» study.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 1006 non-duplicate nosocomial isolates of <em>P. aeruginosa</em> collected in 44 hospitals from 25 cities in Russia in 2015–2016 were studied. Species identification of isolates was performed by means of MALDI-TOF mass-spectrometry. Antimicrobial susceptibility was determined using broth microdilution method according to ISO 20776-1:2006 and interpreted using EUCAST MIC clinical breakpoints v.9.0. The presence of acquired carbapenemase genes of VIM, IMP, NDM, GES-2 and GES-5 groups was determined using real-time PCR. Genotyping of isolates was performed by analysis of selected single nucleotide polymorphisms in 7 chromosomal loci used for multi-locus sequence typing (MLST) of this species.</p> <h3 id="results">Results.</h3> <p><em>P. aeruginosa</em> comprised of 17.4% of all bacterial pathogens isolated within the «MARATHON 2015–2016» study. The resistance rates to antibiotics were (in decreasing order of <em>in vitro</em> activity): 1.4% to colistin, 41.5% to aztreonam, 41.6% to ceftazidime/avibactam, 47.7% to amikacin, 51.5% to cefepime, 54.2% to tobramycin, 55.5% to meropenem, 56.3% to gentamicin, 56.8% to ceftazidime, 62.0% to piperacillin/tazobactam, 63.3% to ciprofloxacin, 65.2% to piperacillin, 67.5% to imipenem, and 97,6% to ticarcillin/clavulanic acid. Acquired carbapenemase genes were detected in 35% of the isolates including those for metallo-β-lactamases of VIM- (30.5%) and IMP-type (0.3%) and for GES-5-like serine carbapenemases. MBL producers were highly resistant to all antibiotics except for aztreonam (49%) and polymyxins (0%); GES-5-producers were resistant to most antibiotics except for aztreonam (4.8%), ceftazidime/avibactam (11.9%) and polymyxins (0%). The majority of carbapenemase producing strains belonged to the international “high-risk” CC235 (76.3%) and CC654 (21%) clones. All CC235 isolates revealed the presence of specific variant of the gene encoding secreted phospholipase A2, ExoU, which is a major virulence factor of <em>P. aeruginosa</em>.</p> <h3 id="conclusions">Conclusions.</h3> <p>The results of this study indicate an increase in resistance rates to most antibiotics, including carbapenems, and in prevalence of carbapenemase production in nosocomial strains of <em>P. aeruginosa</em>. This can be largely attributed to the expansion of “high-risk” clones.</p> http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p147/ Thu, 10 Oct 2019 00:07:00 +0000 http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p147/ <h3 id="objective">Objective.</h3> <p>To assess rates of antimicrobial resistance and production of the clinically important acquired resistance mechanisms (extended spectrum beta-lactamases [ESBL] and carbapenemases) in nosocomial strains of <em>Enterobacterales</em>, and to determine genotypes and prevalence of “international high-risk clones” among carbapenemase-producing <em>Klebsiella pneumoniae</em> isolated in various Russian regions within the “MARATHON 2015–2016“ study.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 2786 non-duplicate nosocomial isolates of <em>Enterobacterales</em>, including 1316 isolates of <em>K. pneumoniae</em> and 837 isolates of <em>Escherichia coli</em> isolated in 49 hospitals from 25 cities in Russia in 2015–2016 were studied. Species identification of isolates was performed using MALDI-TOF mass-spectrometry. Broth microdilution method was used for susceptibility testing and phenotypic ESBL detection. The presence of acquired carbapenemase genes of VIM, IMP, NDM, KPC and OXA-48-groups was determined using real-time PCR. Genotyping of <em>K. pneumoniae</em> isolates was performed by multi-locus sequence typing (MLST) according to the Pasteur institute database and Diancourt et al. method.</p> <h3 id="results">Results.</h3> <p>A total of 48.2% of all bacterial pathogens isolated within the “MARATHON 2015–2016“ study comprised of <em>Enterobacterales</em>. The most common pathogens were <em>K. pneumoniae</em> (47.2%) and <em>E. coli</em> (30.0%). The majority of <em>Enterobacterales</em> isolates were resistant to oxyimino-β-lactam compounds: cefotaxime (78.4%), ceftazidime (67.2%), cefepime (68.4%) and aztreonam (71.5%). ESBL production was determined in 67.8% of isolates. Resistance to carbapenems (imipenem, meropenem and ertapenem) was observed in 6.9%, 6.5% and 23.6% of all <em>Enterobacterales</em> isolates, respectively. A total of 14.4% of <em>Enterobacterales</em> isolates carried the genes of class D carbapenemases OXA-48 (11.4%), class B carbapenemases NDM-1 (2.7%) and class A carbapenemases KPC (&lt; 0.1%). Eight isolates (0.3%) of <em>K. pneumoniae</em> carried the genes of NDM- and OXA-48-like carbapenemases simultaneously and one isolate (&lt; 0.1%) of <em>Proteus mirabilis</em> carried the genes of NDM and VIM metallo-β-lactamases. Most of the 57 genotyped carbapenemase-producing <em>K. pneumoniae</em> isolates belonged to the “international high-risk clones”: CG395 (45.6%), CG11 (12.3%), CG147 (10.5%) and CG307 (10.5%). The most active agents were ceftazidime/avibactam (3.5% of resistant isolates) and aztreonam/avibactam (MIC50 and MIC90 were 0.06 and 0.25 mg/L respectively). Colistin was the most active agent <em>in vitro</em> (18.6% of resistant isolates) among non-β-lactam antibiotics. The only 3.9% of <em>E. coli</em> isolates were resistant to tigecycline. The MIC50/MIC90 values of tigecycline for <em>K. pneumoniae</em> were 0.5 and 2 mg/L and did not exceed ECOFF value (≤ 2 mg/L).</p> <h3 id="conclusions">Conclusions.</h3> <p>The results of this study showed an extremely high prevalence of resistance to most antibiotics, including carbapenems, and a variety of carbapenemase genes in nosocomial isolates of <em>Enterobacterales</em>. It makes a selection of empiric antibiotic treatment extremely difficult and warrants the need for regular resistance surveillance in every hospital.</p> http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p134/ Thu, 10 Oct 2019 00:06:00 +0000 http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p134/ <h3 id="objective">Objective.</h3> <p>To study <em>in vitro</em> activity of antimicrobials against clinical isolates from patients with communityacquired urinary tract infections (UTIs) in different regions of Russia in 2017–2018.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 1052 <em>Enterobacterales</em> isolates collected in the Russian Federation as part of a multicenter, prospective, epidemiological study of the antimicrobial resistance of uropathogens causing community-acquired UTI in different subsets of patients (“DARMIS-2018”) were included in the analysis. Uropathogens were isolated from children and adults of both sexes in all age groups with acute (and recurrences of chronic) community-acquired UTIs, including pregnant women with asymptomatic bacteriuria in 32 centers of 24 cities of Russia in 2017–2018.</p> <h3 id="results">Results.</h3> <p><em>Enterobacterales</em> comprised a total of 90.6% of all isolated bacterial pathogens (90.6% in the adult subset; 89.3% in the pregnant women subset and 93.8% in the children and adolescents subset). The most prevalent species were <em>Escherichia coli</em> (71.3% in the adult subset; 73.6% in the pregnant women subset; 79.7% in the children and adolescents subset) and <em>Klebsiella pneumoniae</em> (11.7% in the adult subset; 10.4% in the pregnant women subset; 7.8% in the children and adolescents subset). The highest activity against <em>E. coli</em> among the oral antimicrobials was demonstrated for fosfomycin (97.7% in the adult subset; 95.9% in the pregnant women subset; 99.0% in the children and adolescents subset) and nitrofurantoin (98.1% in adult subset; 100% in the pregnant women subset; 97.1% in the children and adolescents subset). Among the parenteral antimicrobials, meropenem and amikacin showed the highest activity (99.4% and 97.9% in the adult subset; 99.5% and 99.1% in the pregnant women subset; 100% and 97.1% in the children and adolescents subset, respectively). Ampicillin, amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole demonstrated the lowest <em>in vitro</em> activity against <em>E. coli</em> (less than 80% per each patient subset). The susceptibility of <em>E. coli</em> isolates to ciprofloxacin was 60.6% in the adult subset; 80.0% in the pregnant women subset and 80.4% in the children and adolescents subset. The rates of extended spectrum beta-lactamase production based on the results of phenotypic tests were 27.0% in the adult subset; 8.6% in the pregnant women subset and 23.5% in the children and adolescents subset.</p> <h3 id="conclusions">Conclusions.</h3> <p>Results of this study indicated the increase in resistance of community-acquired isolates of <em>Enterobacterales</em> (particularly <em>E. coli</em>) to the most of antimicrobials in Russia.</p> http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p119/ Thu, 10 Oct 2019 00:04:00 +0000 http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p119/ http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p084/ Thu, 10 Oct 2019 00:01:00 +0000 http://cmac-journal.ru/en/publication/2019/2/cmac-2019-t21-n2-p084/ <h3 id="objective">Objective.</h3> <p>To study management of patients with peptic ulcer based on outpatient card data and to evaluate changes in methods for diagnosis of <em>H. pylori</em> and treatment prescriptions compared with 2004– 2005.</p> <h3 id="materials-and-methods">Materials and Methods.</h3> <p>A total of 100 outpatient cards of patients aged 18 years and older who came to outpatient clinic visit for peptic ulcer over the period of 2015–2018 were analyzed. The results of this study were compared with the data from the pharmacoepidemiological study «Ulcer», which was performed in 2004–2005 in Smolensk.</p> <h3 id="results">Results.</h3> <p>The primary diagnosis of <em>H. pylori</em> in patients with peptic ulcer has been carried out more often over the past 15 years (18% in 2015–2018 vs 4.5% in 2004–2005). Appropriate anti-<em>H. pylori</em> therapy was prescribed in 31% of patients compared to 11% of patients in 2004–2005 (p &lt; 0.01). There were no cases of prescribing drugs with unproven clinical efficacy, such as vitamins, aloe, potato juice, methyluracil, riboxin, etc. In 2004–2005, these drugs were administered to 56.5% of patients. The proportion of proton pump inhibitors and bismuth preparations use increased from 49.2% to 91% and from 7% to 26%, respectively. The incidence of antacid use significantly decreased from 60% to 10%. The proportion of clarithromycin prescriptions increased from 7.7% to 44%, but that of metronidazole prescriptions decreased from 40.6% to 15%. Over the past 15 years, confirmation of <em>H. pylori</em> eradication was performed more often (11% in 2015–2018 vs 1% in 2004–2005).</p> <h3 id="conclusions">Conclusions.</h3> <p>There was an improvement in quality of medical care for patients with peptic ulcer. However, a high frequency of non-compliance with the standards for the diagnosis of <em>H. pylori</em> and peptic ulcer therapy was noted, which warrants additional organizational and educational measures.</p> http://cmac-journal.ru/en/publication/2014/1/cmac-2014-t16-n1-p033/ Sat, 01 Feb 2014 00:04:01 +0000 http://cmac-journal.ru/en/publication/2014/1/cmac-2014-t16-n1-p033/