Effect of a Single Percutaneous Abscess Drainage Puncture and Imipenem Therapy, Alone or in Combination, in Treatment of Mixed-Infection Abscesses in Mice

Abstract

The importance of supplementary imipenem therapy after a single percutaneous abscess drainage puncture was studied in a mouse model of established mixed-infection abscesses. Animals were treated for 3 days with daily dosing regimens of 384 to 1,536 mg/kg of body weight that took into account the short half-life of this antibiotic in mice. Imipenem therapy in conjunction with abscess drainage was significantly better than drainage alone in reducing the Escherichia coli and Bacteroides fragilis counts in the mixed infections. Furthermore, the killing of B. fragilis by the combination of imipenem therapy and abscess drainage was significantly better than that by imipenem treatment alone. The maximum reductions in E. coli and B. fragilis counts were 1.1 and 2.2 log ₁₀ CFU/abscess, respectively. In contrast, the in vitro activity of imipenem was significantly better (maximum reduction, ≥6.2 log ₁₀ CFU/ml) against mixed cultures of the same strains even when bacterial numbers similar to those found in the abscesses were used. Comparable in vivo activity was achieved only when treatment was started 30 min before inoculation (reduction for both strains, ≥6.1 log ₁₀ CFU/abscess), but this killing was significantly diminished if the start of treatment was delayed until ≥12 h after inoculation. Imipenem concentrations in abscess tissue reached levels above the MIC for E. coli for >60% of the dosing interval. Possible reasons for the reduced activity of imipenem in vivo are discussed, and we conclude that standard susceptibility tests overestimate the efficacy of this antibiotic against the organisms present in these abscesses.