Rifkin G D, Silva J, Fekety R
Gastroenterology. 1978 Jan;74(1):52-7.
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.
肠道细菌产生有毒物质是抗生素相关性结肠炎提出的一种致病机制。我们证实在发生克林霉素诱导的小肠结肠炎的仓鼠粪便中存在一种或多种有毒物质。从接受克林霉素治疗动物的盲肠内容物获得的悬液经口胃管给予仓鼠后，在2至4天内可诱发出血性回盲肠炎并导致死亡。腹腔注射这些悬液的无菌滤液可产生渗出性腹膜炎、腹腔内出血，80%至100%的仓鼠在1天内死亡。腹腔注射克林霉素或内毒素（滤液中仅存在少量内毒素）则未观察到这些效应。滤液在体外与多价梭菌抗毒素一起孵育可中和其毒性。滤液在体外与正常马血清一起孵育不会降低其体内毒性。滤液中所含的有毒物质对热不稳定，并在Y-1肾上腺细胞培养物中产生了对热不稳定的肠毒素特有的形态学变化。从接受盐水处理动物获得的盲肠滤液未产生这些效应。这些初步研究表明，可能由梭菌产生的类似肠毒素的物质可能在仓鼠克林霉素诱导的结肠炎发病机制中起重要作用。
