Drug-induced Clostridium difficile-associated disease.

Abstract

Clostridium difficile is a spore-forming anaerobe that resides in the colon and is capable of producing gastrointestinal disease in humans. Factors such as previous exposure to antibacterials and some antineoplastic agents have been reported to promote the overgrowth of C. difficile, with subsequent liberation of potent exotoxins that induce inflammation in the colonic mucosa. Colonisation rates vary, and are higher during infancy and hospitalisation, compared with healthy adults. Although many antibacterials have been reported to induce disease, those agents that achieve high concentrations in the intestinal lumen and are active against bowel flora are more likely to promote overgrowth of C. difficile. Agents with a high potential to induce C. difficile-associated disease (CDAD) include aminopenicillins, cephalosporins and clindamycin. These antibacterials are capable of reducing normal colonisation resistance within the colon. The exact incidence of CDAD is unknown. Some reports suggest an incidence of 1 to 3 infections per 100,000 courses of outpatient oral therapy. The spectrum of illness of CDAD can range from mild diarrhoeal disease to severe colitis, toxic megacolon and sepsis. Fatalities have occurred in some cases. Discontinuation of the offending antibacterial in patients with mild disease is often sufficient to alleviate symptoms. For those with moderate to severe illness, metronidazole and vancomycin are reported to be equally efficacious. Increasing resistance of enterococci to vancomycin limits its use to patients with severe life-threatening infections. Patients with recurrent disease usually respond well to the same course of therapy as was used to treat the initial infection. CDAD is potentially preventable when appropriate antibacterial selection and infection control measures are implemented.