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Antimicrobial Agents and Chemotherapy, December 2002, p. 3712-3718, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3712-3718.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Lorna E. T. Stearne,1* Steven L. Buijk,1 Johan W. Mouton,2 and Inge C. Gyssens1

Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam,1 Department of Medical Microbiology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands2

Received 18 April 2002/ Returned for modification 7 June 2002/ Accepted 27 August 2002

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 log10 CFU/abscess, respectively. In contrast, the in vitro activity of imipenem was significantly better (maximum reduction, >=6.2 log10 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 log10 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.

* Corresponding author. Mailing address: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31-10-4087665. Fax: 31-10-4089454. E-mail: stearne{at}kmic.fgg.eur.nl.

Antimicrobial Agents and Chemotherapy, December 2002, p. 3712-3718, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3712-3718.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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