Evaluation of antimicrobial agents in animal models of infections involving bacteroides fragilis

Antimicrobial agents were examined for relative efficacy against Bacteroides fragilis in two animal models. In one model, rats were challenged with cecal contents intraperitoneally to produce intra-abdominal abscesses containing a mixed aerobic-anaerobic flora. Efficacy of antimicrobials was measured by assessing decrease in mortality and decrease in the incidence of abscess formation. Metronidazole, clindamycin, carbenicillin, moxalactam, cefoxitin, moxalactam, cefoxitin and cefotaxime gave the best results in lowering the rate of abscess formation; these drugs were more effective than cephalothin, cefazolin or cefamandole. The second model involved challenge of mice subcutaneously with a pure culture of B. fragilis to produce a mono-infected, well-encapsulated abscess. Quantitative counts of bacteria were used to assess in-vivo antimicrobial activity. Metronidazole, clindamycin, moxalactam, and cefoxitin were found to be the most effective agents, reducing mean bacterial counts by 10^6.7, 10^5.0, 10^3.8, and 10^3.5, respectively. Thienamycin, cefotaxime, carbenicillin, and ceftizoxime had a significant but less marked effect, while cefoperazone, cephalothin, ceforanide, and ampicillin were relatively inactive against B. fragilis. A delay in treatment of 8 to 120 hours after challenge showed a noticeable reduction in activity, except with metronidazole. It is presumed that bacteria within an abscess are in a stationary growth phase, and this has an important influence on in=vivo efficacy.