title: [In vitro emergence of ertapenem resistance in Escherichia coli producing extended-spectrum β-lactamase].
abstract: BACKGROUND
  The occurrence of community-associated infections due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. These organisms are frequently resistant to many of the antimicrobial agents but remain susceptible to carbapenems. We investigated the in vitro emergence of carbapenem resistance in a collection of clinical isolates of ESBL -producing E. coli.
  
  
  METHODS
  First and second-step resistant mutants were obtained from E. coli with ESBL. Aliquots of 50 μl containing > 109 CFU were applied to Mueller-Hinton plates containing meropenem, imipenem or ertapenem. MICs for native strains and mutants were determined using the epsilometric test (E-test).
  
  
  RESULTS
  Resistant mutants were not selected with imipenem or meropenem. E. coli growth was observed on ertapenem (0.5 mg/L)-containing plates in 13 of 57 clinical isolates (22.8 %).The ertapenem MIC for these first-step mutants were ≥ 1 mg/L, remaining susceptible to imipenem and meropenem. The first-step mutants were used as native strains. Six second-step resistant mutants were selected with ertapenem. All were fully resistant (CMI ≥ 8 mg/L) to ertapenem, three were resistant to meropenem and one to imipenem. Four second-step resistant mutants were selected with meropenem. All were resistant to ertapenem, meropenem, and two of them were resistant to imipenem.
  
  
  CONCLUSIONS
  Stable resistant mutants were easy to select with ertapenem among ESBL-producing E. coli. Two steps were necessary to select resistant mutants to meropenem or imipenem. The use of ertapenem in high-inoculum infections or in undrained focus of infection should be monitored to reduce the risk on selection of resistance.
authors.affiliation: Hugo Edgardo Villar, Departamento de Bacteriología Clínica. Laboratorio Hidalgo, Ladislao Martínez 43 B1640EYA Martínez, Buenos Aires, Argentina. hugo.villar@laboratoriohidalgo.com.
authors.forename: H E
authors.initials: HE
authors.lastname: Villar
authors.forename: M B
authors.initials: MB
authors.lastname: Jugo
authors.forename: M
authors.initials: M
authors.lastname: Visser
authors.forename: M
authors.initials: M
authors.lastname: Hidalgo
authors.forename: G
authors.initials: G
authors.lastname: Hidalgo
authors.forename: G C
authors.initials: GC
authors.lastname: Maccallini
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D000077727:Ertapenem; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology; D015378:Imipenem / Q000494:pharmacology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D009154:Mutation; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D047090:beta-Lactams; D015378:Imipenem; D001618:beta-Lactamases; D000077731:Meropenem; D000077727:Ertapenem