Korean J Lab Med.  2007 Apr;27(2):111-117. 10.3343/kjlm.2007.27.2.111.

In vitro Antimicrobial Synergy against Imipenem-Resistant Acinetobacter baumannii

Affiliations
  • 1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea. mnkim@amc.seoul.kr

Abstract

BACKGROUND: Most imipenem-resistant Acinetobacter baumannii (IRAB) isolates are multiresistant, leaving few options for an effective antimicrobial therapy. We purposed to select possible candidates for the combinations of antimicrobials that are synergistic in vitro for inhibitory or bactericidal activities against IRAB and evaluate the usefulness of double disk synergy test (DDS) in predicting synergistic bactericidal activity. METHODS: Fifty-five IRAB isolates recovered from patients during the period from August 1999 to November 2000 were tested for susceptibilities to amikacin, gentamicin, tobramycin, piperacillin, piperacillin/tazobactam, cefotaxime, cefepime, cefoperazone/sulbactam (C/S), imipenem, meropenem, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, chloramphenicol, minocycline, and colistin by the Clinical and Laboratory Standard Institute agar dilution method. Three isolates showing different susceptibility profiles were tested for antimicrobial synergy by DDS and then by timekill study (TKS) using DDS-positive combinations. RESULTS: Colistin, C/S, and minocycline were active in 50 (90.9%), 50, and 44 (80.0%) isolates, respectively, and all the other drugs were active in less than 20% of isolates. Minocycline-imipenem, minocycline-C/S, minocycline-amikacin, imipenem-tobramycin, C/S-amikacin, and C/S-tobramycin combinations showed synergistic inhibitory or bactericidal activity by TKS when the same combinations were synergistic in DDS; however, C/S-imipenem was found synergistic on DDS, but not by TKS. CONCLUSIONS: Colistin, C/S, and minocycline were relatively active against IRAB. DDS might help predict the synergistic antimicrobial effect of TKS if one of the combinations was susceptible.

Keyword

Imipenem-resistant; Acinetobacter baumannii; Atimicrobial synergy; Double disk synergy; Time kill study

MeSH Terms

Acinetobacter baumannii/*drug effects/isolation & purification
Anti-Bacterial Agents/*pharmacology
Drug Resistance, Bacterial
Drug Synergism
Humans
Imipenem/*pharmacology
Microbial Sensitivity Tests
Time Factors

Figure

  • Fig. 1. Double disk synergy tests of three A. baumannii isolates. (A) The isolate 1 showed synergy at the combination of MC+IP, IP+C/S, and C/S+AK. (B) The isolate 2 showed synergy at the combination of MC+IP, MC+C/S, MC+AK, IP+AK, IP+TM, IP+C/S, C/S +TM, and C/S+AK. (C) The isolate3 showed synergy at the combination of MC+AK, IP+AK, and IP+C/S. The black dots denote synergy between the two drugs.

  • Fig. 2. Time-kill tests for three A. baumannii isolates. (A) IRAB1 showed synergistic killing at the combination of MC+IP, MC+AK, and C/S+AK. (B) IRAB2 showed synergistic killing at the combination of MC+IP, MC+TM, MC+C/S, MC+AK, IP+TM, C/S+TM, and C/S+AK. (C) IRAB3 showed no synergistic killing at any combination of antimicrobials. The number in parentheses denotes the concentration (μg/mL) of antimicrobials tested.


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