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.The accepted treatment for patients with small intra-abdominal abscesses involves ultrasound-or computed tomographyguided percutaneous abscess drainage followed by an intensive course of antimicrobial therapy (12). However, the importance of supplementary antibiotic therapy and determination of whether it is beneficial to the further eradication of abscesses have not been extensively studied in animal models (11), even though such studies could provide useful information for the clinician. Furthermore, the selection of the dosing regimen of an antibiotic would normally be based on the in vitro susceptibilities of the individual bacterial strains determined with standard (10 5 CFU/ml) inocula, even though standard MICs may not be predictive of a successful outcome (16).Previously, using a mouse model of subcutaneous (s.c.) abscesses, we have studied the efficacies of antimicrobials in the treatment of small well-established mixed-infection abscesses (17). Five days of treatment with very high doses of a broadspectrum quinolone (well into the range of murine toxicity) were necessary to obtain reductions of more than 2 log 10 CFU/ abscess for both Escherichia coli and Bacteroides fragilis as well as significant reductions in abscess weight and inflammation.The aim of the present study was to compare the effect of a single percutaneous abscess drainage puncture and imipenem therapy, either alone or in com...