title: Heteroresistance to meropenem in carbapenem-susceptible Acinetobacter baumannii.
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.
authors.affiliation: University of Thessaly, Mezourlo, Larissa, Greece. ado@med.uth.gr
authors.forename: Alexandros
authors.initials: A
authors.lastname: Ikonomidis
authors.forename: Evangelia
authors.initials: E
authors.lastname: Neou
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Gogou
authors.forename: Georgia
authors.initials: G
authors.lastname: Vrioni
authors.forename: Athanassios
authors.initials: A
authors.lastname: Tsakris
authors.forename: Spyros
authors.initials: S
authors.lastname: Pournaras
mesh_terms: D000151:Acinetobacter Infections / Q000453:epidemiology / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D006115:Greece / Q000453:epidemiology; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D013845:Thienamycins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D000077731:Meropenem