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J Antimicrob Chemother. 2011 Mar;66(3):611-7. doi: 10.1093/jac/dkq470. Epub 2010 Dec 21.

Efficacy of carbapenems against a metallo-β-lactamase-producing Escherichia coli clinical isolate in a rabbit intra-abdominal abscess model.

Author information

1
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

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.

PMID:
21177674
DOI:
10.1093/jac/dkq470
[Indexed for MEDLINE]

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