Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing
ISSN:
1312-773X (Online)
Issue:
2018, vol. 24, issue4
Subject Area:
Medicine
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DOI:
10.5272/jimab.2018244.2258
Published online: 03December 2018
Original article
J of IMAB. 2018 Oct-Dec;24(4):2258-2266
ANTIBIOTIC COMBINATIONS WITH COLISTIN AGAINST CARBAPENEM-RESISTANT Klebsiella pneumoniae - in vitro ASSESSMENT
Yuliya Marteva-Proevska1, 2 , Tzvetan Velinov1, Rumyana Markovska2, Diliyana Dobrikova1, Ivan Pavlov1, Lyudmila Boyanova2, Ivan Mitov2,
1) Central Laboratory of Clinical Microbiology, University Multiprofile Hospital for Active Treatment Alexandrovska, Sofia, Bulgaria.
2) Department of Medical Microbiology, Faculty of Medicine, Medical University of Sofia, Bulgaria.
ABSTRACT:
Purpose: The treatment of infections, caused by highly resistant strains of Gram-negative bacteria is extremely difficult. A potentially valuable option is combination antibiotic therapy. The aim of this study was to evaluate three different in vitro methods for synergy testing and to assess the effect of different combinations with colistin against carbapenem-resistant K. pneumoniae strains.
Material/methods: A screening test for synergy with colistin (developed in the laboratory) and the microdilution method of El-Azizi were used on 50 carbapenem-resistant strains of K. pneumoniae. Additionally, time-kill assays (TKA) were performed for one antibiotic combination.
Results: A total of 16 combinations were tested with the screening test. Synergy and probable synergy with colistin were observed mainly with azithromycin (18% of the isolates), rifampicin (16%), meropenem (14%) and doxycycline (12.8%). The combinations colistin-rifampicin, colistin-meropenem and colistin-gentamicin, were synergistic in 36%, 8% and 20%, respectively, according to the microdilution method of El-Azizi. The observed synergy was detected mainly against some of the colistin resistant strains. Agreement between the two methods was found in 80% for the combinations colistin-rifampicin and colistin-meropenem and in 84% for colistin-gentamicin. Agreement between the three methods used was observed for four strains (80%).
Conclusions: The screening test may represent a rapid and cost effective screening of a large number of combinations with colistin. The microdilution method of El-Azizi may provide an opportunity for rapid testing of three double and one triple antibiotic combinations in one plate. There is an urgent need for standardization of the methods for synergy testing and guidelines for diagnostic laboratories.
Keywords: combination therapy, in vitro assessment, colistin, K.pneumoniae, microdilution method El-Azizi,
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Please cite this article as: Marteva-Proevska Y, Velinov T, Markovska R, DobrikovaD, Pavlov I, Boyanova L, Mitov I. Antibiotic combinations with colistin against carbapenem-resistant Klebsiella pneumoniae - in vitro assessment. J of IMAB. 2018 Oct-Dec;24(4):2258-2266. DOI: 10.5272/jimab.2018244.2258
Correspondence to: Yuliya Marteva-Proevska, MD., Central Laboratory of Clinical Microbiology, UMHAT Alexandrovska;
1, St Georgi Sofiiski Str., Sofia, Bulgaria
; E-mail: proevska@abv.bg
REFERENCES:
1. Elemam A, Rahimian J, Doymaz M. In vitro evaluation of antibiotic synergy for polymyxin B-resistant carbapenemase-producing Klebsiella pneumoniae. J Clin Microbiol. 2010 Oct;48(10):3558-62. [PubMed]
2. Rahal JJ. Antimicrobial Resistance among and Therapeutic Options against Gram-Negative Pathogens, Clin Infect Dis. 2009 Aug 15; 49 Suppl 1:S4-S10. [PubMed] [Crossref]
3. Doern CD. When does 2 plus 2 equal 5? A review of antimicrobial synergy testing, J Clin Microbiol. 2014 Dec; 52 (12):4124-4128.
4. El-Azizi M. Novel Microdilution Method to Assess Double and Triple Antibiotic Combination Therapy In Vitro. Int J Microbiol. 2016;2016:4612021. [PubMed] [Crossref].
5. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 7.1, 2017. [Internet]
6. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 8.1, 2018. [Internet]
7. CLSI-EUCAST Polymyxin Breakpoints Working Group. Recommendations for MIC determination of colistin (polymyxin E) as recommended by the joint CLSI-EUCAST Polymyxin Breakpoints Working Group. EUCAST. 22 March 2016. [Internet]
8. International Standards Organisation. Clinical laboratory testing and in vitro diagnostic test systems - Susceptibility testing of infectious agents andevaluation of performance of antimicrobial susceptibility test devices. Part 1: Reference method for testing the in vitro activity of antimicrobial agents against rapidly growing aerobic bacteria involved in infectious diseases. ISO 20776-1:2006. [Internet]
9. Lagerbäck P, Khine WWT, Giske CG, Tangdén T. Evaluation of antibacterial activities of colistin, rifampicin and meropenem combinations against NDM-1-producing Klebsiella pneumoniae in 24h in vitro time-kill experiments, J Antimicrob Chemother. 2016 Aug;71:2321-5. [PubMed]
10. Tängdén T, Hickman RA, Forsberg P, Giske CG, Cars O. Evaluation of double- and triple-antibiotic combinations for VIM- and NDM-producing Klebsiella pneumoniae by in vitro time-kill experiments, Antimicrob agents and chemother. 2014; 58(3):1757-62. [PubMed] [Crossref]
11. Poirel L, Savov E, Nazli A, Trifonova A, Todorova I, Gergova I, et al. Outbreak caused by NDM-1- and RmtB-producing Escherichia coli in Bulgaria. Antimicro Agents Chemother. 2014Apr;58(4):2472–4. [PubMed] [Crossref]
12. Kostyanev T, Strateva T, Xavier BB, Marteva-Proevska Y, Lammens C, Markova B, et al. Detection and characterization of two NDM-1-producing Klebsiella pneumoniae strains from Bulgaria. J Antimicrob Chemother. 2016; May;71(5):1428–1430. [PubMed] [Crossref]
13. Todorova B, Sabtcheva S, Ivanov IN, Lesseva M, Chalashkanov T, Ioneva M, et al. First clinical cases of NDM-1-producing Klebsiella pneumoniae from two hospitals in Bulgaria. J Infect Chemother. 2016 Dec;22(12):837–840. [PubMed] [Crossref]
14. Savov E, Politi L, Spanakis N, Trifonova A, Kioseva E, Tsakris A. NDM-1 Hazard in the Balkan States: Evidence of the First Outbreak of NDM-1-Producing Klebsiella pneumoniae in Bulgaria. Microb Drug Resist. 2018 Apr;24(3):253-259. [PubMed] [Crossref]
15. Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis. 2005 May;40(9):1333-41. [PubMed] [Crossref]
16. Meletis G, Tzampaz E, Sianou E, Tzavaras I, Sofianou D. Colistin heteroresistance in carbapenemase-producing Klebsiella pneumoniae. J Antimicrob Chemother 2011 Apr; 66 (4):946-7. [PubMed] [Crossref]
17. Band VI, Satola SW, Burd EM, Farley MM, Jacob JT, Weiss DS. Carbapenem resistant Klebsiella pneumoniae exhibiting clinically undetected colistin heteroresistance leads to treatment failure in a murine model of infection.MBio 2018 Mar -Apr; 9 (2):e02448-17. [PubMed] [CrossRef]
18. Poudyal A, Howden BP, Bell JM, Gao W, Owen RJ, Turnidge JD, et al. In vitro pharmacodynamics of colistin against multidrug-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2008 Dec;62(6):1311-8. [PubMed] [Crossref]
19. Choi MJ, Ko KS. Mutant prevention concentrations of colistin for Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae clinical isolates, J Antimicrob Chemother. 2014 Jan;69(1):275-7. [PubMed] [Crossref]
20. Tängdén T. Combination antibiotic therapy for multidrug resistant Gram-negative bacteria. Ups J Med Sci. 2014 May;119:149-53. [PubMed]
21. Sopirala MM, Mangino JE, Gebreyes WA, Biller B, Bannerman T, Balada-Llasat JM, et al. Synergy testing by Etest, microdilution checkerboard, and time-kill methods for pan-drug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2010 Nov;54:4678-83. [PubMed]
22. Bratu S, Tolaney P, Karumudi U, Quale J, Mooty M, Nichani S, et al. Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents. J Antimicrob Chemother. 2005 Jul;56(1):128-32. [PubMed] [Crossref]
23. Urban C, Mariano N, Rahal JJ. In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Antimicrob Agents Chemother. 2010 Jun;54(6):2732-4. [PubMed] [Crossref]
24. Lin L, Nonejuie P, Munguia J, Hollands A, Olson J, Dam Q, et al. Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against HighlyMultidrug-Resistant Gram-Negative Bacterial Pathogens. EBioMedicine. 2015 Jun;2(7):690-8. [PubMed]
25. Gaibani P, Lombardo D, Lewis RE, Mercuri M, Bonora S, Landini MP, et al. In vitro activity and post-antibiotic effects of colistin in combination with other antimicrobials against colistin-resistant KPC-producing Klebsiella pneumoniae bloodstream isolates, J Antimicrob Chemother. 2014 Jul;69(7):1856-65. [PubMed]
26. Diep JK, Jacobs DM, Sharma R, Covelli J, Bowers DR, Russo TA, et al. Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B-Resistant KPC-Producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2017 Jan;61(2): pii: e02121-16. [PubMed] [Crossref].
Received: 10 August 2018
Published online: 03 December 2018
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