Comparative efficacy of antibiotics in treating experimental Clostridium septicum infection

Abstract

Clostridium septicum is a highly pathogenic microbe that causes gas gangrene in humans, and is the principal cause of spontaneous gas gangrene in patients with gastrointestinal maladies, including adenocarcinoma of the colon. Despite modern approaches to manage C. septicum infection, morbidity and mortality remain high (>60%). At present, no objective in-vivo data exist supporting the current antibiotic treatment recommendations for C. septicum infection. Utilizing an established murine model of clostridial myonecrosis, this study investigated the efficacy of standard antibiotics for anaerobic Gram-positive soft tissue infections (penicillin, clindamycin, tetracycline and vancomycin) in treating C. septicum gas gangrene. Following intramuscular challenge with 1 × 106 colony-forming units of C. septicum, antibiotics were administered by intraperitoneal injection every 4 h for a total of four doses. At 30 h, all animals in all treatment groups survived the C. septicum challenge, compared with no survivors in the untreated controls (100% mortality by 10 h). However, by 60 h, mice treated with vancomycin exhibited 40% mortality, with no mortality observed in any other antibiotic treatment group. Microbroth dilution minimum inhibitory concentration analyses for three strains of C. septicum also demonstrated high susceptibility to penicillin, clindamycin and tetracycline, but considerably lower susceptibility to vancomycin. This study suggests that penicillin, clindamycin and tetracycline are suitable alternatives for the treatment of C. septicum infection in humans.