title: Efficacy of carbapenems against a metallo-β-lactamase-producing Escherichia coli clinical isolate in a rabbit intra-abdominal abscess model.
abstract: BACKGROUND
  Although metallo-β-lactamases (MBLs) hydrolyse most β-lactams, including carbapenems, MBL-producing Enterobacteriaceae very often remain susceptible to carbapenems in vitro. We studied the in vivo efficacy of imipenem, meropenem, ertapenem and aztreonam against a carbapenem-susceptible MBL-producing clinical Escherichia coli strain in a rabbit intra-abdominal abscess model.
  
  
  METHODS
  Rabbits were inoculated intraperitoneally with 10(8) cfu/mL of VIM-1-positive E. coli and were assigned to receive no treatment (controls) or intravenous imipenem/cilastatin (imipenem) 70 mg/kg/12 h or meropenem 125 mg/kg/12 h or ertapenem 60 mg/kg/12 h or aztreonam 70 mg/kg/12 h. Dosing regimens were chosen on the basis of preliminary pharmacokinetic studies so that T(>MIC) was achieved for ≥50% of the dosing interval for all tested antibiotics. A total of eight doses were administered before sacrifice and the abscesses were harvested and quantitatively cultured.
  
  
  RESULTS
  MICs of imipenem, meropenem, ertapenem and aztreonam for the infecting isolate were 1, ≤0.25, 1.5 and ≤0.25 mg/L, respectively. The log(10) cfu/g (mean ± SD) viable counts in pus were as follows: controls (n = 16), 8.71 ± 1.34 (P < 0.001 versus all other groups); imipenem (n = 15), 4.89 ± 2.42; meropenem (n = 15), 4.24 ± 2.44; ertapenem (n = 16), 3.17 ± 1.85 (P = 0.022 versus imipenem); and aztreonam (n = 15), 3.62 ± 3.05. Mortality among treated rabbits was significantly reduced compared with controls. Four animals in the aztreonam group (26.7%) had culture-negative pus and no mortality was noted among aztreonam-treated animals.
  
  
  CONCLUSIONS
  In the rabbit experimental model, carbapenems were shown to be effective in the treatment of intra-abdominal infection due to an extended-spectrum β-lactamase-negative carbapenem-susceptible VIM-1-producing clinical E. coli strain, but treatment with aztreonam resulted in a more favourable outcome overall.
authors.affiliation: 4th Department of Internal Medicine, Athens University School of Medicine, University General Hospital Attikon, 1 Rimini Str., 124 62 Chaidari, Greece. msouli@med.uoa.gr
authors.forename: Maria
authors.initials: M
authors.lastname: Souli
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Konstantinidou
authors.forename: Ira
authors.initials: I
authors.lastname: Tzepi
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.forename: Angelos
authors.initials: A
authors.lastname: Pefanis
authors.forename: Zoi
authors.initials: Z
authors.lastname: Chryssouli
authors.forename: Irene
authors.initials: I
authors.lastname: Galani
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giamarellos-Bourboulis
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D018784:Abdominal Abscess / Q000188:drug therapy*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D015780:Carbapenems / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008297:Male; D011817:Rabbits; D012376:Rodent Diseases / Q000188:drug therapy*; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D001618:beta-Lactamases