EFFICACY OF AMPICILLIN/SULBACTAM FOR THE TREATMENT OF EXPERIMENTAL INTRAABDOMINAL SEPSIS

Studies using an experimental model for intra-abdominal sepsis in rats have documented the efficacy of several therapeutic regimens that is comparable to the efficacy reported for similar types of infections in patients. Previous studies have indicated that antimicrobial agents with activity against coliforms reduce the mortality associated with the acute peritonitis phase of infection in this model system, and agents effective against obligate anaerobes, including Bacteroides fragilis, reduce the incidence of abscesses in surviving animals. Individual broad-spectrum antimicrobial agents with activity against both obligate anaerobes and facultative gram-negative rods have also been shown to provide effective therapy in this model system. Preliminary studies with the combination of ampicillin and a beta-lactamase inhibitor, sulbactam, suggested that this combination was an effective therapeutic regimen in this animal model. The present study includes a more detailed evaluation of this regimen and explores the ability of ampicillin to retain biologic activity within formed abscesses. The results indicate that ampicillin/sulbactam therapy compares favorably with established treatment regimens in preventing both acute lethality during the early phase of disease and subsequent abscess development. In addition, it has been shown, through the use of a sensitive bioassay system and by high-performance liquid chromatographic methods, that abscess levels of ampicillin approximate serum levels measured at the same time. These data suggest that sulbactam is effective in preventing the degradation of ampicillin within the abscess cavity when administered concomitantly.