Inciting and etiologic agents of colitis.

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.

Clostridium difficile colitis associated with cancer chemotherapy.

Administration of cancer chemotherapeutic agents to humans and animals is frequently complicated by diarrhea and enterocolitis. Clostridium difficile and its toxin were found in the stools of two patients with colitis after chemotherapy for malignant neoplasms. Diarrhea in both patients resolved with oral vancomycin hydrochloride therapy. Clostridium difficile was also isolated from several fomites within the room of one of these patients and also from the hands of his nurses. Based on these two recent experiences, we believe patients with cancer and diarrhea or signs suggestive of colitis should be studied for toxigenic C difficile and appropriate isolation techniques employed.

Epidemiology of antibiotic-associated colitis; isolation of Clostridium difficile from the hospital environment.

Clostridium difficile is the most important cause of antibiotic-associated colitis. Using selective media, it was found that contamination with this organism was common in the environment of patients in the hospital with the disease. It was often found on floors, hoppers, toilets, bedding, mops, scales and furniture. This organism was also present on these items, but less often, in areas in which patients known to carry this hardy spore-forming organism had not been detected. Air, food and walls were negative. The organism was isolated from the hands and stools of asymptomatic hospital personnel. It was also found on surfaces in a patient's home. The importance of the various sources of the organism in its spread in the hospital is not known, and further studies are needed. It is suggested that enteric isolation precautions, and careful handwashing and cleansing of potentially contaminated surfaces and objects may be worthwhile when cases of antibiotic-associated colitis are identified.

Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis.

Clostridium difficile is the most important cause of antibiotic-associated colitis, but its epidemiology remains unknown. Using a selective medium for the isolation of C. difficile, cultures were obtained from the environment and contacts of hospitalized patients carrying C. difficile in their stools. In areas where carriers had diarrhea, 85 (9.3%) of 910 cultures of floors and other surfaces, especially those subject to fecal contamination, were positive. In areas where there were no known carriers, only 13 (2.6%) of 497 cultures of similar sites were positive (P less than 0.005). C difficile was isolated from hands and stools of asymptomatic hospital personnel, from sewage and soil, and from the home of a patient. Environmental isolates were toxigenic. C. difficile inoculated onto a floor persisted there for five months. Further studies are needed to document how often floor persisted there for five months. Further studies are needed to document how often C. difficile shed by patients with antibiotic-associated colitis is acquired by other persons and whether isolation precautions are capable of limiting the organism's spread.

Studies on the epidemiology of antibiotic-associated Clostridium difficile colitis.

Vancomycin protects hamsters from the development of Clostridium difficile colitis after treatment with clindamycin, and vancomycin is useful in treatment of humans with the disease. Relapses have occurred in both hamsters and humans when vancomycin is discontinued. Vancomycin appears to enhance susceptibility to colonization with C. difficile by eliminating competing intestinal organisms. The nature of these organisms is not known, but various tools are now available to aid in identifying them. Cancer chemotherapeutic agents should be added to the list of factors such as surgery and antibiotics that may predispose to emergence of C. difficile. The number of organisms required for colonization of antibiotic-treated hamsters is low and cross-infection seems to play a role in the disease in hamster colonies. The organism can be detected on surfaces in rooms of patients with the disease, and on the hands of personnel caring for them. Outbreaks of the disease have been recognized. Our results suggest isolation precautions should be used to prevent spread of the organism from patients with the disease to others being treated with antibiotics.