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Inciting and etiologic agents of colitis
Abstract:
Since 1979, 3,115 stool samples were tested for detection of Clostridium difficile and its cytotoxin; these were obtained from patients who had drug-related diarrhea. Presumed or proven colitis due to C. difficile was diagnosed in 130 patients. Drugs implicated most commonly as causing or associated with the onset of enterocolitis due to C. difficile were ampicillin (38 episodes), cephalosporins (71), clindamycin (36), and the aminoglycosides (45). The hamster model of colitis was employed to explore the role of other inducing agents. Altering the usual diet of hamsters to one with a higher protein content decreased the 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 ml per 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 cytotoxic drugs 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.
Insights
A study of 3,115 stool samples found that various drugs, including antibiotics and antineoplastics, can trigger Clostridium difficile colitis. Dietary changes and certain cathartics also play a role in inducing this condition.
Area of Science:
- Microbiology
- Gastroenterology
- Pharmacology
Background:
- Clostridium difficile (C. difficile) is a significant cause of infectious diarrhea and colitis.
- Drug-induced enterocolitis is a recognized clinical problem.
- The role of various agents in inducing C. difficile colitis requires further elucidation.
Purpose of the Study:
- To identify drugs and other factors associated with Clostridium difficile colitis.
- To investigate the role of inducing agents in a hamster model of colitis.
Main Methods:
- Analysis of 3,115 stool samples from patients with drug-related diarrhea.
- Diagnosis of C. difficile colitis in 130 patients.
- Use of a hamster model to test inducing agents like antibiotics, cytotoxic drugs, diet alterations, and cathartics.
Main Results:
- Antibiotics (ampicillin, cephalosporins, clindamycin, aminoglycosides) were most commonly implicated in C. difficile colitis.
- A high-protein diet and cefazolin administration shortened survival time in hamsters.
- Castor oil and vegetable oil improved survival against clindamycin-induced colitis, while Milk of Magnesia and mineral oil did not.
- Methotrexate induced C. difficile cecitis in hamsters, preventable by folinic acid or vancomycin.
Conclusions:
- A wide range of factors, including antibiotics, antineoplastic agents, cathartics, and dietary modifications, can induce C. difficile colitis.
- The hamster model is useful for studying the pathogenesis of C. difficile colitis.
- Understanding these triggers is crucial for preventing and managing C. difficile infections.