Activity of Antimicrobial Combinations Against Extensively Drug-Resistant Acinetobacter baumannii as Determined by Checkerboard Method and E-test

Sunee  Limsrivanichakorn; Popchai  Ngamskulrungroj; Amornrut  Leelaporn

doi:10.33192/Smj.2020.29

Authors

Sunee Limsrivanichakorn Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand http://orcid.org/0000-0002-1449-2240
Popchai Ngamskulrungroj Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand http://orcid.org/0000-0001-5162-5498
Amornrut Leelaporn Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand http://orcid.org/0000-0003-3989-151X

DOI:

https://doi.org/10.33192/Smj.2020.29

Keywords:

Synergy test, XDR Acinetobacter baumannii, colistin, cefoperazone/sulbactam, moxifloxacin

Abstract

Objective: Combination therapy is needed to treat extensively drug-resistant (XDR) Acinetobacter baumannii infection. Colistin (Col) in combination with another drug is usually used for that purpose. The aim of this study was to determine the activity of antimicrobial combinations against XDR A. baumannii using both standard checkerboard (CB) method and E-test. E-test was also evaluated for application in a diagnostic bacteriology laboratory by comparing its efficacy with that of CB method.
Methods: Eighty clinical isolates of XDR A. baumannii were used to determine the activity of the following antimicrobial combinations by CB method and E-test: Col+cefoperazone/sulbactam (Cps), Cps+moxifloxacin (Mox), and Col+Mox. Comparison of CB and E-test was also evaluated.
Results: By CB method, Col+Cps yielded a synergistic effect rate (12.5%) higher than those of the other 2 combinations (CpS+Mox 5% and Col+Mox 0%). The majority of test results revealed additivity. Col+Cps, Cps+Mox, and Col+Mox exhibited additive effect against 78.75%, 85.0%, and 87.5% of isolates, respectively. Overall, E-test and CB yielded only 37.5% concordant rates. However, high concordant rates were specifically observed in additive effect of Col+Cps (73.8%) and Cps+Mox (80.4%).
Conclusion: Col+Cps exhibited better activity than the other two combinations against XDR A. baumannii. E-test is the method that should be used, but its use is limited to the additive results of Col+Cps and Cps+Mox.

References

1. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: Emergence of a Successful Pathogen. Clin Microbiol Rev 2008;21:538-82.
2. Spence RP, Towner KJ. Frequencies and mechanisms of resistance to moxifloxacin in nosocomial isolates of Acinetobacter baumannii. J Antimicrob Chemother 2003;52:687-90.
3. Li T, Sheng M, Gu T, Zhang Y, Yirepanjiang A, Li Y. In vitro assessment of cefoperazone-sulbactam based combination therapy for multidrug-resistant Acinetobacter baumannii isolates in China. J Thorac Dis 2018;10:1370-6.
4. Penwell WF, Shapiro AB, Giacobbe RA, Gu RF, Gao N, Thresher J, et al. Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii. Antimicrob Agents Chemother 2015;59:1680-9.
5. 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;54:4678-83.
6. Bonapace CR, White RL, Friedrich LV, Bosso JA. Evaluation of antibiotic synergy against Acinetobacter baumannii: a comparison with Etest, time-kill, and checkerboard methods. Diagn Microbiol Infect Dis 2000;38:43-50.
7. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 29th ed. Wayne, PA: CLSI; 2019.
8. Dafopoulou K, Zarkotou O, Dimitroulia E, Hadjichristodoulou C, Gennimata V, Pournaras S, et al. Comparative evaluation of colistin susceptibility testing methods among carbapenem-nonsusceptible Klebsiella pneumoniae and Acinetobacter baumannii clinical isolates. Antimicrob Agents Chemother 2015;59:4625-30.
9. Hindler JA, Humphries RM. Colistin MIC variability by method for contemporary clinical isolates of multidrug-resistant Gram-negative bacilli. J Clin Microbiol 2013;51:1678-84.
10. Ma F, Shen C, Zheng X, Liu Y, Chen H, Zhong L, et al. Identification of a novel plasmid carrying mcr-4.3 in an Acinetobacter baumannii strain in China. Antimicrob Agents Chemother 2019;63.
11. Marie M, Krishnappa L, Alzahrani A, Mubaraki M, Alyousef A. A prospective evaluation of synergistic effect of sulbactam and tazobactam combination with meropenem or colistin against multidrug-resistant Acinetobacter baumannii. Bosn J Basic Med Sci 2015;15:24-9.
12. Tan TY, Lim TP, Lee WH, Sasikala S, Hsu LY, Kwa AL. In vitro antibiotic synergy in extensively drug-resistant Acinetobacter baumannii: the effect of testing by time-kill, checkerboard, and Etest methods. Antimicrob Agents Chemother 2011;55:436-8.
13. Claeys KC, Fiorvento AD, Rybak MJ. A review of novel combinations of colistin and lipopeptide or glycopeptide antibiotics for the treatment of multidrug-resistant Acinetobacter baumannii. Infect Dis Ther 2014;3:69-81.
14. Jiang Z, He X, Li J. Synergy effect of meropenem-based combinations against Acinetobacter baumannii: a systematic review and meta-analysis. Infect Drug Resist 2018;11:1083-95.
15. Zhu W, Wang Y, Cao W, Cao S, Zhang J. In vitro evaluation of antimicrobial combinations against imipenem-resistant Acinetobacter baumannii of different MICs. J Infect Public Health 2018;11:856-60.
16. Bae S, Kim MC, Park SJ, Kim HS, Sung H, Kim MN, et al. In vitro synergistic activity of antimicrobial agents in combination against clinical isolates of colistin-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2016;60:6774-9.
17. Liang W, Liu XF, Huang J, Zhu DM, Li J, Zhang J. Activities of colistin- and minocycline-based combinations against extensive drug resistant Acinetobacter baumannii isolates from intensive care unit patients. BMC Infect Dis 2011;11:109.