Antibiotic-induced lethal enterocolitis in hamsters: studies with eleven agents and evidence to support the pathogenic role of toxin-producing Clostridia

Abstract

Clindamycin-induced enterocolitis in hamsters was studied, using a tissue culture assay to detect clostridial toxin. It was found that animals with lethal enterocolitis had a cytopathogenic substance in cecal contents and blood that was neutralized by clostridial antitoxins. Cultures of the cecal flora yielded numerous species of clostridia, but only 1 organism was detected which produced a toxin which was cytopathic in tissue culture. This organism, Clostridium difficile, was consistently present in high concentrations, and the cell-free supernate of these strains caused enterocolitis if injected intracecally into hamsters. Ten additional antimicrobials were tested ih hamsters. Ampicillin, vancomycin, erythromycin, cephalosporins, and oral gentamicin caused lethal enterocolitis in most recipients, and all animals which died had evidence of clostridia toxin in cecal contents at necropsy. Tetracycline and metronidazole were well tolerated, and the animals given these antimicrobials had no evidence of the toxin. We conclude that toxin-producing clostridia are responsible for lethal enterocolitis due to a variety of antimicrobials in hamsters.