Gastrointestinal and systemic toxicity of fecal extracts from hamsters with clindamycin-induced colitis

Abstract

The production of toxic substances by intestinal bacteria is one pathogenic mechanism proposed for antibiotic-associated colitis. We demonstrated the presence of a toxic substance(s) in the feces of hamsters developing clindamycin-induced enterocolitis. Suspensions derived from cecal contents of clindamycin-treated animals induced a hemorrhagic ileocecitis and death within 2 to 4 days after being given orogastrically to hamsters. Intraperitoneal injection of sterile filtrates of these suspensions produced an exudative peritonitis, intraabdominal hemorrhages, and death of 80 to 100% of hamsters within 1 day. These effects were not seen with intraperitoneal injection of clindamycin or endotoxin, only small amounts of which were present in the filtrate. Incubation of the filtrate in vitro with polyvalent clostridial antitoxin neuralized its toxicity. In vitro incubation of the filtrate with normal equine serum did not reduce its in vivo toxicity. The toxic substance(s) contained in the filtrate was heat-labile and produced morphological changes in Y-1 adrenal cell cultures characteristic of heat-labile enterotoxins. Cecal filtrates obtained from saline-treated animals produced none of these effects. These preliminary studies suggest that enterotoxin-like substances, possibly produced by clostridia, may play an important role in the pathogenesis of clindamycin-induced colitis in the hamster.