Research Articles






Mehmet Esadoglu, Burcin Ozer, Nizami Duran


ABSTRACT: Background: Multiple-drug resistance of Acinetobacter species cause difficulties in the treatment of infections. Due to decrease in success rates with monotherapy combinations that show synergistic effect in the treatment of MDR Acinetobacter infections is used. Objectives: The study aimed to investigate the efficacy of meropenem and amikacin combinations against metallo-beta-lactamase (MBL)-producing Acinetobacter strains isolated from clinical specimens. Method: The presence of MBL in strains was detected by gradient diffusion method (GDM). Fifty MBL-positive and 50 MBL-negative strains were included in the study. The activity of meropenem-amikacin combination against MBL-positive isolates was investigated by both GDM and the checkerboard method while the activity against MBL-negative isolates was investigated by the checkerboard method. Results: Additive or indifferent interactions between meropenem and amikacin were detected in 38 (76%) of the 50 MBL-positive strains, synergistic interactions were detected in 7(14%), and antagonistic interactions were detected in 5(10%) using GDM. Using the checkerboard method, additive or indifferent interactions between the drugs were detected in 37 (74%) and synergistic interactions in 13 (26%) of 50 MBL-positive strains while synergistic interactions were observed in 36 (72%) and additive or indifferent interactions in 14 (28%) of 50 MBL-negative strains. No antagonistic interaction was detected in the MBL-positive and MBL-negative strains using the checkerboard method. In MBL-positive strains no difference was found between the results of checkerboard and GDM. Conclusion: Based on our detection of 72% synergistic interactions between meropenem and amikacin on MBL-positive strains in the Gold Standard checkerboard assay, it is concluded that in vitro evidence supports meropenem and amikacin combination therapy against non–MBL-producing Acinetobacter spp. but further clinical studies are needed.

KEY WORDS: Acinetobacter, MDR, gradient diffusion method, Multiple-drug resistance


  1. Maragakis LL, Perl TM. : Epidemiology, antimicrobial resistance and treatment options. Clin Infect Dis. 2008;46:1254–1263.

  2. Deveci O, Dal T, Tekin R, Bozkurt F, Tekin A, Dayan S. Carbapenem resistance in Acinetobacter baumannii: Where is it heading? Infez Med. 2013;21(3):211–215.

  3. Viehman JA, Nguyen MH, Doi Y. Treatment Options for Carbapenem-Resistant and Extensively Drug-Resistant Acinetobacter Drugs. 2014 August ; 74(12): 1315–1333

  4. Vaneechoutte M, Dijkshoorn L, Nemec A, Kämpfer P, Wauters G. Acinetobacter, chryseobacterium, moraxella, and other nonfermentative gram-negative rods. In Versalovic J, Carroll KC, Funke G, Jorgensen JH, Landry ML, Warnock DW, editors. Manual of clinical microbiology. Volume 1. 10th ed. Washington, DC: ASM Press; 2011, p. 714–738.

  5. Gordon NC, Wareham DW. Multidrug-resistant : Mechanisms of virulence and resistance. . 2010;35:219–226.

  6. Esposito S, De Simone G. Update on the main MDR pathogens: Prevalence and treatment options. Infez Med. 2017;25(4):301–310.

  7. Walsh TR, Bolmstrom A, Qwärnstrom A, Gales A. Evaluation of a new etest for detecting metallo – Lactamases in routine clinical testing. J Clin Microbiol. 2002;40:2755–2759.

  8. Moody J. Synergism testing: Broth microdilution checkerboard and broth macrodilution methods. In: Isenber HD, editor. Clincal microbiology procedures handbook. Volume 2. 2nd edition. Washington: ASM Press; 2004. p.5.12.1-5.12.23

  9. Sopirala, MM, Mangino JE, Gebreyes WA, et al. Si. 54:4678–4683.

  10. Dundar D, Otkun M. In-vitro efficacy of synergistic antibiotic combinations in multidrug resistant Pseudomonas aeruginosa strains. . 2010;51(1):111–116.

  11. Kaleem F, Usman J, Hassan A, Khan A. Frequency and susceptibility pattern of metallo beta lactamase producers in a hospital in Pakistan. Infect Dev Ctries. 2010;23:810–813.

  12. Gupta V, Sidhu S, Chander J. Metallo- β-lactamase producing non-fermentative gram-negative bacteria: An increasing clinical threat among hospitalized patients. Asian Pac J Trop Med. 2012;5:718–721.

  13. Kiratisin P, Apisarnthanarak A, Kaewdaeng S. Synergistic activities between carbapenems and other antimicrobial agents against Acinetobacter baumannii including multidrug-resistant and extensively drug-resistant isolates. . 2010;36:243–246.

  14. Marques MB, Brookings ES, Moser SA, Sonke PB, Waites KB. Comparative in vitro antimicrobial susceptibilities of nosocomial isolates of and synergistic activities of nine antimicrobial combinations. 1997;41(5):881–885.

  15. Ozseven AG, Cetin ES, Arıdogan BC, Ozseven L. In vitro synergistic activity of carbapenems in combination with other antimicrobial agents against multidrug-resistant Acinetobacter baumannii. Afr J Microb Res. 2012;6:2985–2987.

  16. Ko WC, Lee HC, Chiang SR, et al. In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain. J Antimicrob Chemother. 2004;53:393–395.

  17. Petrosillo N, Chinello P, Proietti MF, et al. Combined colistin and rifampicin therapy for carbapenem-resistant Acinetobacter baumannii infections: Clinical outcome and adverse events. Eur Soc Clin Microbiol Infect Dis. 2005;11:682–684.

  18. 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;55:436–437.