Prevention of clindamycin-induced colitis in hamsters by Clostridium sordellii antitoxin

Abstract

Toxins produced by Clostridium difficile have been implicated in the etiology of antibiotic-induced colitis. Clostridium difficile antitoxin is not available, but recent studies have shown that toxins present in the feces of patients with this disease are neutralized by Clostridium sordellii antitoxin. We found that C. sordellii antitoxin neutralized toxins produced in broth cultures of either C. sordellii or C. difficile and that passive immunization with C. sordellii antitoxin before challenge with clindamycin prevented colitis in hamsters. Significantly fewer antitoxin-treated animals than unimmunized controls developed diarrhea and died with hemorrhagic colitis. Administration of 300 U of antitoxin parenterally either on the day of challenge with clindamycin or 24 hr later provided significant protection (25% mortality vs. 100% mortality in controls, P < 0.01). None of eight animals given antitoxin (300 U) both on the day of challenge and 24 hr later died. Filtrates prepared from cecal contents of dead or killed hamsters were tested for toxicity by intraperitoneal injection into hamsters and by addition to monolayers of monkey kidney cells. Fecal filtrates from antitoxin-protected animals were not toxic in these assays, but filtrates from control animals were uniformly toxic. Passive immunization against clostridial toxins was protective against clindamycin-associated colitis in this model. This finding further substantiates the importance of these toxins in the pathogenesis of antibiotic-induced colitis.