In vitro time-kill studies of antimicrobial agents against blood isolates of imipenem-resistant Acinetobacter baumannii, including colistin- or tigecycline-resistant isolates

J Med Microbiol. 2012 Mar;61(Pt 3):353-360. doi: 10.1099/jmm.0.036939-0. Epub 2011 Oct 20.

Abstract

The emergence of colistin or tigecycline resistance as well as imipenem resistance in Acinetobacter baumannii poses a great therapeutic challenge. The bactericidal and synergistic effects of several combinations of antimicrobial agents against imipenem-, colistin- or tigecycline-resistant A. baumannii isolates were investigated by in vitro time-kill experiments. Six imipenem-resistant A. baumannii blood isolates were examined in this study, including colistin- and tigecycline-susceptible, colistin-resistant but tigecycline-susceptible, and colistin-susceptible but tigecycline-resistant isolates. Time-kill studies were performed using five antimicrobial agents singly or in combinations (imipenem plus colistin, imipenem plus ampicillin-sulbactam, colistin plus rifampicin, colistin plus tigecycline, and tigecycline plus rifampicin) at concentrations of 0.5× and 1× their MICs. Only imipenem was consistently effective as a single agent against all six A. baumannii isolates. Although the effectiveness of combinations of 0.5× MIC antimicrobial agents was inconsistent, combination regimens using 1× MIC of the antimicrobial agents displayed excellent bactericidal activities against all six A. baumannii isolates. Among the combinations of 0.5× MIC antimicrobial agents, the combination of colistin and tigecycline showed synergistic or bactericidal effects against four of the isolates. This in vitro time-kill analysis suggests that antimicrobial combinations are effective for killing imipenem-resistant A. baumannii isolates, even if they are simultaneously resistant to either colistin or tigecycline. However, the finding that the combinations of 0.5× MIC antimicrobial agents were effective on only some isolates may warrant further investigation of the doses of combination agents needed to kill resistant A. baumannii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / isolation & purification
  • Anti-Bacterial Agents / pharmacology
  • Bacteremia / microbiology
  • Blood / microbiology*
  • Colistin / pharmacology*
  • Drug Resistance, Multiple, Bacterial*
  • Drug Synergism
  • Humans
  • Imipenem / pharmacology*
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects*
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Tigecycline
  • Time Factors

Substances

  • Anti-Bacterial Agents
  • Tigecycline
  • Imipenem
  • Minocycline
  • Colistin