In vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin against carbapenem-resistant Acinetobacter baumannii clinical isolates

Diagn Microbiol Infect Dis. 2018 Jun;91(2):169-174. doi: 10.1016/j.diagmicrobio.2018.01.008. Epub 2018 Jan 31.

Abstract

Carbapenem-resistant Acinetobacter baumannii clinical isolates (n=23) were investigated for carbapenem resistance mechanisms and in vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin. Major carbapenem resistance mechanism was OXA-23 production. The vast majority of these isolates were OXA-23-producing A. baumannii ST195 and ST542, followed by novel STs, ST1417, and ST1423. The interuption of carO by a novel insertion sequence, ISAba40, was found in two isolates. The combinations of imipenem and fosfomycin, meropenem and amikacin, imipenem and amikacin, and imipenem and colistin were synergistic against carbapenem-resistant A. baumannii by 65.2%, 46.2%, 30.8%, and 17.4%, respectively. Surprisingly, the combination of imipenem and fosfomycin was the most effective in this study against A. baumannii, which is intrinsically resistant to fosfomycin. Imipenem and fosfomycin inhibit cell wall synthesis; therefore, fosfomycin may be an adjuvant and enhance the inhibition of cell wall synthesis of carbapenem-resistant A. baumannii when combined with imipenem.

Keywords: Acinetobacter baumannii; Antibiotic combination; Carbapenem resistance.

MeSH terms

  • Acinetobacter Infections / microbiology*
  • Acinetobacter baumannii* / drug effects
  • Acinetobacter baumannii* / genetics
  • Amikacin / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / pharmacology*
  • Colistin / pharmacology
  • Fosfomycin / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Thailand
  • beta-Lactam Resistance / genetics*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Fosfomycin
  • Amikacin
  • Colistin