Relative Efficacy of β-Lactam Antimicrobial Agents in Two Animal Models of Infections Involving Bacteroides fragilis

Abstract

Antimicrobial agents of the β-lactam class were examined for relative efficacy against Bacteroides fragilis in two animal models. One model used rats challenged with pooled cecal contents to produce intraabdominal sepsis involving a polymicrobial aerobicanaerobic flora. The outcome, based on mortality rates and the incidence of intraabdominal abscesses, showed optimal results with carbenicillin, moxalactam, cefoxitin, and cefotaxime. Reduction in the incidence of abscesses was significantly better with use of these agents than with cefazolin, cephalothin, or cefamandole. A second model consisted of subcutaneous abscesses involving B. fragilis in mice; quantitative analysis of bacteria was used for evaluation of in vivo activity. The results indicate that clindamycin, moxalactam, and cefoxitin reduced mean counts by 105.0, 103.8, and 103.5, respectively. Additional β-lactam antimicrobial agents that caused a significant, but less pronounced, decrease in counts were thienamycin, cefotaxime, carbenicillin, and ceftizoxime. Cefoperazone, cephalothin, ceforanide, and ampicillin proved relatively inactive against B. fragilis in this model. The activity of cefoperazone was significantly increased by the addition of a β-lactamase inhibitor. Comparative efficacy of 10 β-lactam antimicrobial agents in the soft-tissue abscess model showed a reasonably good correlation with peak serum levels and median minimal inhibitory concentrations.