Comparative efficacy of cefoperazone, cefoperazone plus sulbactam, ciprofloxacin, clindamycin, metronidazole, and penicillin G against anaerobic bacteria in an animal model.

Treatment efficacy of various antimicrobial regimens against anaerobes was studied in semipermeable chambers simulating a closed-space, locally neutropenic infection site in rabbits. Bacteroides fragilis, Bacteroides melaninogenicus, Clostridium perfringens, and Peptostreptococcus anaerobius were inoculated (at a mean of 5.3 log10 CFU/ml in prereduced pooled rabbit serum) into the chambers (one isolate per chamber) in triplicate. Antimicrobial therapy consisted of cefoperazone, cefoperazone plus sulbactam, ciprofloxacin, clindamycin, metronidazole (against the gram-negative anaerobes), or penicillin G (against the gram-positive anaerobes), beginning 4 hours after organism inoculation and continuing every 6 hours for 16 doses. With the use of anaerobic techniques for specimen acquisition, transport, and culture, quantitative bacterial findings were measured at the start of therapy and at various time points thereafter. Antibiotic concentrations were measured in blood and chamber fluid by liquid chromatography or bioassay methods. At the end of the study in vivo organisms were reduced by at least 3 log10 CFU/ml from drug-free growth control chambers by all the antimicrobial regimens tested except for cefoperazone against B. fragilis and ciprofloxacin against the three isolates tested. The addition of sulbactam to cefoperazone inhibited B. fragilis beta-lactamase activity and eradicated B. fragilis in vivo. In vivo results with this model confirmed in vitro susceptibilities of all tested antimicrobials except ciprofloxacin and should provide useful indications of the potential clinical efficacy of other new agents against anaerobes.