Inciting and Etiologic Agents of Colitis

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Abstract
Since 1979, 3,115 stool samples were tested for detection of Clostridium difficile and its cytotoxin; these wereobtained from patients who had drug-related diarrhea. Presumed or provencolitis due to C. difficile wasdiagnosed in 130patients. Drugs implicated most commonly as causing or associated with the onset of enterocolitis due to C. difficile wereampicillin (38 episodes), cephalosporins (71), clindamycin (36), and the aminoglycosides (45). The hamster model of colitis was employedto explorethe role of other inducing agents. Altering the usual diet of hamsters to one with a higher protein content decreasedthe time to death due to C. difficile cecitis following the administration of cefazolin (10 mg). Several cathartics also were studied for their effect on the lethality of antibiotic-induced cecitis. Daily administrations of castor oil (0.5 mlper day) and vegetable oil (1.0 ml per day) improved survival against lethal doses of clindamycin. Milk of magnesia or mineral oil provided no protection. Four patients with C. difficile colitis induced by therapy with cytotoxicdrugs also were identified. Methotrexate induced cecitis when administered orally and daily to hamsters, and C. difficile and its cytotoxin were identified in the hamsters' stools. Death due to methotrexate-induced cecitis was prevented by daily administration of folinic acid or vancomycin. These data demonstrate that a variety of antibiotics, antineoplastic agents, cathartics, and diet changes can induce C. difficile colitis in humans and hamsters.

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