Comparative in vitro antimicrobial susceptibilities and synergistic activities of antimicrobial combinations against carbapenem-resistant Acinetobacter species: Acinetobacter baumannii versus Acinetobacter genospecies 3 and 13TU

Abstract

Therapeutic options for the treatment of infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are limited. In vitro activity of amikacin, ciprofloxacin, colistin (polymyxin E), ampicillin-sulbactam, and tigecycline alone and in combination with imipenem against CRAB and carbapenem-resistant Acinetobacter genospecies 3 and 13TU was investigated. Colistin (97% susceptible) and tigecycline (88% and 44% susceptible by US Food and Drug Administration [FDA] and European Committee on Antimicrobial Susceptibility Testing [EUCAST] breakpoints for Enterobacteriaceae, respectively) were the 2 most active agents against CRAB, followed by minocycline (66%), ampicillin/sulbactam (16%), and amikacin (13%). Compared with CRAB isolates, carbapenem-resistant Acinetobacter genospecies 3 and 13TU isolates had higher antimicrobial susceptible rates to ciprofloxacin (88%), amikacin (63%), tigecycline (100% by FDA breakpoint and 88% by EUCAST breakpoint for Enterobacteriaceae, respectively), minocycline (100%), and ampicillin/sulbactam (75%). For the 12 tested CRAB isolates, the checkerboard titration method demonstrated synergy between imipenem and colistin (42%), tigecycline (25%), amikacin (16%), and ampicillin/sulbactam (16%). Time-kill assays revealed antimicrobial synergism for imipenem in combination with colistin (75%), tigecycline (50%), ampicillin/sulbactam (42%), amikacin (42%), and ciprofloxacin (16%). However, antimicrobial synergism between imipenem and combined agents was not present among CRAB isolates with an imipenem MIC ≥32 mg/L. The combination of tigecycline and colistin showed good in vitro synergy for CRAB with high imipenem resistance. Our results demonstrate accurate identification of prevalent Acinetobacter species and highlight their different antimicrobial susceptibilities. This knowledge will enable clinicians to select appropriate regimens for treating these infections.