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.