CMAC 2026; 28(1) on КМАХ

Antimutant activity of the combination of colistin and rifaximin in selective digestive decontamination: validation in a dynamic flow-through system

Thu, 28 May 2026 10:50:08 +0000

Objective.

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 Klebsiella pneumoniae and Pseudomonas aeruginosa, 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 in vitro 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 K. pneumoniae and P. aeruginosa.

Materials and Methods.

The study included 10 clinical isolates of K. pneumoniae (producers of NDM, KPC, OXA-48, KPC+NDM) and 10 clinical isolates of P. aeruginosa (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.

Results.

MPC of colistin for K. pneumoniae strains ranged from 64 to 128 mg/L, for P. aeruginosa – 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 K. pneumoniae and 2–8-fold for P. aeruginosa. 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.

Conclusions.

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 K. pneumoniae and P. aeruginosa, which opens prospects for its clinical use in regions with high prevalence of antibiotic-resistant pathogens.

Lower respiratory tract microbiome in patients with pulmonary tuberculosis and HIV coinfection

Thu, 28 May 2026 10:47:54 +0000

Objective.

To investigate the bacterial and fungal microbiota of the lower respiratory tract in hospitalized patients with tuberculosis and HIV coinfection.

Materials and Methods.

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).

Results.

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 C. albicans). Bacterial microbiota constituted 51.1%, represented by Enterobacteriaceae (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.

Conclusions.

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 Mycobacterium tuberculosis, 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.

Immunogenetic predictors of severe sepsis: role of functional polymorphisms

Thu, 28 May 2026 10:45:55 +0000

Objective.

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.

Materials and Methods.

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).

Results.

The most significant predictor of an unfavorable course is the MCP1 -2518A> 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> G is protective against septic shock (OR = 0.42; p = 0.02) and AKI (OR = 0.34; p = 0.007); c.536T > C is associated with mortality (OR = 3.7; p = 0.02). Opposite effects of IL18: -607C >A – risk of renal replacement therapy (OR = 3.3; p = 0.008) and mechanical ventilation (OR = 2.4; p = 0.009); -137G > C – protection against these complications (OR = 0.46 and 0.32, respectively). The context dependence of TNFα -308G >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> G, c.596C > T) and IL18 (-137G > C) were associated with the risk of sepsis recurrence (OR = 4.0; p = 0.03). The TLR4 variant c.*1205G >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 > T was associated with reduced risk of chronic critical illness (OR = 0.36; p = 0.0054).

Conclusions.

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.

Etiological structure of community-acquired urinary tract infections in children and adolescents in Krasnoyarsk region and antibiotic resistance of the leading pathogen – Escherichia coli

Thu, 28 May 2026 10:43:50 +0000

Objective.

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.

Materials and Methods.

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.

Results.

Escherichia coli was the leading etiological pathogen of community-acquired UTI in Krasnoyarsk region. Klebsiella pneumoniaе and Enterococcus spp. accounted in the 2-3 place in etiological structure. Of the parenteral agents, antimicrobial resistance of E. coli to meropenem was absent. The maximal sensitivity E. coli was noted for ampicillin-sulbactam and amikacin. Antimicrobial resistance of E. coli 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 E. coli was preserved.

Conclusions.

According to the data on antibacterial resistance of E. coli 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%.

Contribution of antimicrobial use surveillance to the prevention of resistance selection

Thu, 28 May 2026 10:41:16 +0000

Machine learning methods in predicting antimicrobial resistance

Thu, 28 May 2026 10:39:07 +0000

Evaluation of linezolid pharmacokinetics and pharmacodynamics in preterm infants

Thu, 28 May 2026 10:35:41 +0000

Objective.

To study pharmacokinetics (PK) and develop a pharmacokinetic/pharmacodynamic (PK/PD) model of linezolid for preterm infants, based on therapeutic drug monitoring (TDM) data.

Materials and Methods.

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.

Results.

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.

Conclusions.

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.

Resolution of the Round Table Pneumonia. From penicillin to the present day: what has changed over the last hundred years

Thu, 28 May 2026 10:30:10 +0000

Etiological structure of respiratory tract infections in patients of different age groups with primary ciliary dyskinesia

Thu, 28 May 2026 10:27:57 +0000

Objective.

To study etiological structure of respiratory tract infections in patients with primary ciliary dyskinesia (PCD) across different age groups.

Materials and Methods.

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.

Results.

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 S. aureus 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, P. aeruginosa predominated – in 80.4% of cases. Antibiotic susceptibility testing using the disk diffusion method revealed that 24.4% of S. aureus isolates were multidrug-resistant, while among P. aeruginosa isolates, 33.3% were multidrug-resistant. Among fungal pathogens, fungi of the genera Candida and Aspergillus were most frequently isolated.

Conclusions.

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: S. aureus – 53.8%; P. aeruginosa – 38.7%; H. influenzae – 21.4%; S. pneumoniae – 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 P. aeruginosa.

Current concepts of the role of viruses as an etiological factor in sepsis

Thu, 28 May 2026 10:24:49 +0000

Local treatment of wound infection: what’s new in the last decade?

Thu, 28 May 2026 10:22:21 +0000

Genome-based analysis of the taxonomic structure of the genus Stenotrophomonas

Thu, 28 May 2026 10:19:27 +0000

Objective.

To analyze the current taxonomic structure of the genus Stenotrophomonas based on genomic data, taking into account limitations associated with nomenclatural validation processes.

Materials and Methods.

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.

Results.

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.

Conclusions.

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.

CMAC 2026; 28(1) on КМАХ

Antimutant activity of the combination of colistin and rifaximin in selective digestive decontamination: validation in a dynamic flow-through system

Objective.

Materials and Methods.

Results.

Conclusions.

Lower respiratory tract microbiome in patients with pulmonary tuberculosis and HIV coinfection

Objective.

Materials and Methods.

Results.

Conclusions.

Immunogenetic predictors of severe sepsis: role of functional polymorphisms

Objective.

Materials and Methods.

Results.

Conclusions.

Etiological structure of community-acquired urinary tract infections in children and adolescents in Krasnoyarsk region and antibiotic resistance of the leading pathogen – *Escherichia coli*

Objective.

Materials and Methods.

Results.

Conclusions.

Contribution of antimicrobial use surveillance to the prevention of resistance selection

Machine learning methods in predicting antimicrobial resistance

Evaluation of linezolid pharmacokinetics and pharmacodynamics in preterm infants

Objective.

Materials and Methods.

Results.

Conclusions.

Resolution of the Round Table Pneumonia. From penicillin to the present day: what has changed over the last hundred years

Etiological structure of respiratory tract infections in patients of different age groups with primary ciliary dyskinesia

Objective.

Materials and Methods.

Results.

Conclusions.

Current concepts of the role of viruses as an etiological factor in sepsis

Local treatment of wound infection: what’s new in the last decade?

Genome-based analysis of the taxonomic structure of the genus Stenotrophomonas

Objective.

Materials and Methods.

Results.

Conclusions.

Etiological structure of community-acquired urinary tract infections in children and adolescents in Krasnoyarsk region and antibiotic resistance of the leading pathogen – Escherichia coli