Heteroresistance to meropenem in carbapenem-susceptible Acinetobacter baumannii

J Clin Microbiol. 2009 Dec;47(12):4055-9. doi: 10.1128/JCM.00959-09. Epub 2009 Oct 14.

Abstract

The characteristics of carbapenem heteroresistance were studied in 14 apparently carbapenem-susceptible Acinetobacter baumannii isolates. The MICs for carbapenems were determined, and the isolates were genotyped by pulsed-field gel electrophoresis (PFGE) and sequence typing (ST). Population analysis, testing of the stability of the heteroresistant subpopulations, and time-killing assays were performed. The agar dilution MICs of both imipenem and meropenem for the native isolates ranged from 0.25 to 4 mg/liter. The isolates belonged to nine PFGE types and exhibited seven ST allelic profiles. Population analysis revealed subpopulations that grew in the presence of imipenem at concentrations of up to 8 mg/liter and meropenem at concentrations of up to 32 mg/liter. The meropenem-heteroresistant subpopulations of 11 isolates exhibited stable resistance with MICs that ranged from 16 to >32 mg/liter; their PFGE profiles were identical to those of the native isolates. Time-kill assays with meropenem revealed less pronounced killing for 10 isolates. These findings indicate that meropenem pressure can produce meropenem-heteroresistant subpopulations that might subsequently select for highly resistant strains.

MeSH terms

  • Acinetobacter Infections / epidemiology
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / classification
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / pharmacology*
  • Drug Resistance, Multiple, Bacterial*
  • Electrophoresis, Gel, Pulsed-Field
  • Greece / epidemiology
  • Humans
  • Meropenem
  • Microbial Sensitivity Tests
  • Polymerase Chain Reaction
  • Thienamycins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Thienamycins
  • Meropenem