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

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 signifcantly reduced compared with controls. Four animals in the aztreonam group (26.7%) had culture-negative pus and no mortality was noted among aztreonamtreated 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.