Potentiation of antimicrobial activity of colistin with antibiotics of different groups against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa | CMAC

Potentiation of antimicrobial activity of colistin with antibiotics of different groups against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa

Clinical Microbiology and Antimicrobial Chemotherapy. 2020; 22(2):128-136

​ Tapalskiy D.V., Petrovskaya T.A., Kozlova A.I., Edelstein M.V.
10.36488/cmac.2020.2.128-136
Klebsiella pneumoniae Acinetobacter baumannii Pseudomonas aeruginosa antimicrobial resistance colistin macrolides carbapenems
Section
Antimicrobials
Type
Original Article
Publication
Clinical Microbiology and Antimicrobial Chemotherapy. 2020; 22(2):128-136

Objective.

To reveal antibiotics being capable of potentiating the antimicrobial activity of colistin against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa.

Materials and Methods.

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 K. pneumoniae, A. baumannii and P. aeruginosa. Bactericidal activity of colistin, carbapenems, clarithromycin and their combinations were also determined at fixed PK/PD breakpoint concentrations of antibiotics.

Results.

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 K. pneumoniae and A. baumannii. In the presence of fixed concentrations of azithromycin (2 mg/L) or clarithromycin (1 mg/L), the colistin MICs decreased 64–512 times for K. pneumoniae, 4–32 times for A. baumannii, 16–64 times for P. aeruginosa. Two- or more-fold reduction of MIC of colistin in the presence of 1 mg/L clarithromycin was observed for 85.2% of K. pneumoniae, 86.3% of A. baumannii and 60.2% of P. aeruginosa 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% K. pneumoniae, 98.0% A. baumannii and 61.3% P. aeruginosa. Colistin-based combinations with clarithromycin-meropenem and clarithromycin-doripenem were bactericidal against most isolates of A. baumannii and P. aeruginosa (91.4–100%), and against colistin-sensitive K. pneumoniae (95.3%) and colistin-resistant K. pneumoniae (79.1%).

Conclusions.

The ability of macrolides to significantly potentiate the colistin antimicrobial activity against both colistin-sensitive and colistin-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa 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.

Dmitry V. Tapalskiy

Gomel State Medical University, Gomel, Belarus

Petrovskaya T.A.

Gomel State Medical University, Gomel, Belarus

Kozlova A.I.

Gomel State Medical University, Gomel, Belarus

Mikhail V. Edelstein

Institute of Antimicrobial Chemotherapy, Smolensk, Russia

  • 1. Shek E.A., Tapalski D.V., Skleenova E.Yu., Sukhorukova M.V., Karpov I.A., Edelstein M.V. Genetic diversity of Acinetobacter baumannii strains producing carbapenemases in Belarus: the role of "international high-risk clones" in the spread of resistance to carbapenems. Immunopatologija, allergologija, infektologija. 2018;2:59-64. DOI: 10.14427/jipai.2018.2.59
  • 2. Tapalski D.V., Osipov V.A., Yevseyenko E.O., Saveliyeva A.K., Kozlovskaya I.V., Kozik A.P., et al. Metallo-beta-lactamases and other carbapenemases among extreme antibiotic-resistant Klebsiella pneumoniae: occurrence in Belarus. Zdravoohranenie. 2017;3:40-47.
  • 3. Chew K.L., La M.V., Lin R.T.P., Teo J.W.P. Colistin and polymyxin B susceptibility testing for carbapenem-resistant and mcr-positive Enterobacteriaceae: comparison of Sensititre, MicroScan, Vitek 2, and Etest with broth microdilution. J Clin Microbiol. 2017;55(9):2609-2616. DOI: 10.1128/JCM.00268-17
  • 4. Zavascki A.P., Bulitta J.B., Landersdorfer C.B. Combination therapy for carbapenem-resistant Gram-negative bacteria. Expert Rev Anti Infect Ther. 2013;11(12):1333-1353. DOI: 10.1586/14787210.2013.845523
  • 5. Zusman O., Avni T., Leibovici L., Adler A., Friberg L., Stergiopoulou T., et al. Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems. Antimicrob Agents Chemother. 2013;57(10):5104-5111. DOI: 10.1128/AAC.01230-13
  • 6. Nastro M., Rodriguez C.H., Monge R., Zintgraff J., Neira L., Rebollo M., et al. Activity of the colistin-rifampicin combination against colistin-resistant, carbapenemase-producing Gramnegative bacteria. J Chemother. 2014;26(4):211-216. DOI: 10.1179/1973947813Y.0000000136
  • 7. Pankey G.A., Ashcraft D.S. Detection of synergy using the combination of polymyxin B with either meropenem or rifampin against carbapenemase-producing Klebsiella pneumoniae. Diagn Microbiol Infect Dis. 2011;70(4):561-564. DOI: 10.1016/j.diagmicrobio.2011.05.003
  • 8. Corbett D., Wise A., Langley T., Skinner K., Trimby E., Birchall S., et al. Potentiation of antibiotic activity by a novel cationic peptide: potency and spectrum of activity of SPR741. Antimicrob Agents Chemother. 2017;61(8):e00200-17. DOI: 10.1128/AAC.00200-17
  • 9. ISO 20776-1:2006 Clinical laboratory testing and in vitro diagnostic test systems – Susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices – Part 1: Reference method for testing the in vitro, 2006. Available at: www.iso.org/standard/41630.html. Accessed October 01, 2019.
  • 10. European Committee on Antimicrobial Susceptibility testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Ver. 9.0., 2019. Available at: www.eucast.org/clinical_breakpoints/. Accessed October 01, 2019.
  • 11. Laishram S., Pragasam A.K., Bakthavatchalam Y.D., Veeraraghavan B. An update on technical, interpretative and clinical relevance of antimicrobial synergy testing methodologies. Indian J Med Microbiol. 2017;35(4):445-468. DOI: 10.4103/ijmm.IJMM_17_189
  • 12. Tapalski D.V. Susceptibility to antibiotic combinations among nosocomial carbapenemase-producing Gram-negative bacteria isolated in Belarus. Klinicheskaja mikrobiologija i antimikrobnaja himioterapija. 2018;20(3):182-191. Russian. DOI: 10.36488//cmac.2018.3.182191
  • 13. Aaron S.D., Ferris W., Henry D.A., Speert D.P., Macdonald N.E. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1206-1212. DOI: 10.1164/ajrccm.161.4.9907147
  • 14. Aaron S.D., Vandemheen K.L., Ferris W., Fergusson D., Tullis E., Haase D., et al. Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial. Lancet. 2005;366(9484):463-471. DOI: 10.1016/S01406736(05)67060-2
  • 15. Kadar B., Kocsis B., Toth A., Damjanova I., Szasz M., Kristof K., et al. Synergistic antibiotic combinations for colistin-resistant Klebsiella pneumoniae. Acta Microbiol Immunol Hung. 2013;60(2):201-209. DOI: 10.1556/AMicr.60.2013.2.10
  • 16. Vidaillac C., Benichou L., Duval R.E. In vitro synergy of colistin combinations against colistin-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae isolates. Antimicrob Agents Chemother. 2012;56(9):4856-4861. DOI: 10.1128/AAC.05996-11
  • 17. MacNair C.R., Stokes J.M., Carfrae L.A., Fiebig-Comyn A.A., Coombes B.K., Mulvey M.R., et al. Overcoming mcr-1 mediated colistin resistance with colistin in combination with other antibiotics. Nat Commun. 2018;9(1):458. DOI: 10.1038/s41467-018-02875-z
  • 18. Francisco G.R., Bueno M.F.C., Cerdeira L., Lincopan N., Ienne S., Souza T.A., et al. Draft genome sequences of KPC-2and CTX-M-15-producing Klebsiella pneumoniae ST437 isolated from a clinical sample and urban rivers in Sao Paulo, Brazil. J Glob Antimicrob Resist. 2019;16:74-75. DOI: 10.1016/j.jgar.2018.12.003
  • 19. Lomonaco S., Crawford M.A., Lascols C., Timme R.E., Anderson K., Hodge D.R., et al. Resistome of carbapenem- and colistinresistant Klebsiella pneumoniae clinical isolates. PLoS One. 2018;13(6):e0198526. DOI: 10.1371/journal.pone.0198526
  • 20. Weng X.B., Mi Z.H., Wang C.X., Zhu J.M. Draft genome sequence of a Klebsiella pneumoniae strain (new sequence type 2357) carrying Tn3926. Genome Announc. 2016;4(5):e0098616. DOI: 10.1128/genomeA.00986-16
  • 21. Yang Y., Higgins C.H., Rehman I., Galvao K.N, Brito I.L., Bicalho M.L., et al. Genomic diversity, virulence, and antimicrobial resistance of Klebsiella pneumoniae strains from cows and humans. Appl Environ Microbiol. 2019;85(6):e02654-18. DOI: 10.1128/AEM.02654-18
  • 22. Abdelsalam M.F.A., Abdalla M.S., El-Abhar H.S.E. Prospective, comparative clinical study between high-dose colistin monotherapy and colistin-meropenem combination therapy for treatment of hospital-acquired pneumonia and ventilatorassociated pneumonia caused by multidrug-resistant Klebsiella pneumoniae. J Glob Antimicrob Resist. 2018;15:127-135. DOI: 10.1016/j.jgar.2018.07.003
  • 23. Eelek S.D. Principles and problems of combined antibiotic therapy. Postgrad Med J. 1956;32(396):324-327. DOI: 10.1136/pgmj.32.369.324
  • 24. Ocampo P.S., Lazar V., Papp B., Arnoldini M., Abel zur Wiesch P., Busa-Fekete R., et al. Antagonism between bacteriostatic and bactericidal antibiotics is prevalent. Antimicrob Agents Chemother. 2014;58(8):4573-4582. DOI: 10.1128/AAC.02463-14
  • 25. Kadar B., Szasz M., Kristof K., Pesti N., Krizsan G, Szentandrassy J., et al. In vitro activity of clarithromycin in combination with other antimicrobial agents against biofilm-forming Pseudomonas aeruginosa strains. Acta Microbiol Immunol Hung. 2010;57(3):235-245. DOI: 10.1556/AMicr.57.2010.3.8
Views
0 Abstract
0 PDF
0 Crossref citations
Shared