Clostridium difficile-Associated Diarrhea — The New Scourge of the Health Care Facility

Clostridium difficile had its name coined because of the difficulty in its isolation. It was first isolated and described in the mid-1930s and later identified as the etiological agent of pseuodomembranous colitis. The organism, which has been isolated from soil, sand, hay and animal dung, is a Grampositive, spore forming, anaerobic bacillus which produces toxin-mediated diarrhea or pseudomembranous colitis. The organism is now well recognized as the major (if not the only) and most important cause of infectious diarrhea occurring in hospitalized patients in developed countries (1). After colonizing the gastrointestinal tract of humans, the organism causes a wide array of manifestations, ranging from asymptomatic colonization to severe diarrhea, pseudomembranous colitis, toxic megacolon, intestinal perforation and death from secondary sepsis. Two recent publications, one by the Society of Healthcare Epidemiology of America (2) and the other by the American College of Gastroenterology (3), have provided detailed information regarding definitions, diagnosis, management (3) and control strategies for C difficile, and have proven to be useful guidelines for healthcare professionals. However, despite the large amount of data regarding C difficile and its associated diseases, it is troubling that its frequency still continues to increase. It is timely to review new developments in the pathogenesis and epidemiology of C difficile-associated diarrhea (CDAD) and explore the reasons for its apparent increase in the Canadian healthcare setting. It was previously thought that C difficile was acquired after some period of hospitalization, resulting in asymptomatic colonization by C difficile. The disease developed after antimicrobials were administered that altered the normal colonic flora, allowing the rapid growth of toxin producing strains of C difficile. However, it is now hypothesized that hospitalized patients are intermittently exposed to C difficile throughout their hospitalization but do not acquire C difficile until after receiving antimicrobials; they then develop disease after a brief incubation period (4-6). Recent data from several longitudinal studies suggest that colonized patients are actually at decreased risk for developing symptomatic disease (7). The studies followed 618 noncolonized patients for over 1000 observation weeks and 192 colonized patients for 282 observation weeks. The studies differentiated between those with primary asymptomatic colonization and those who remained culture positive after the resolution of CDAD. It is thought that additional factors related to host immunity or the type and timing of antimicrobial exposure are necessary for C difficile disease to occur. The antibiotics most commonly implicated in C difficile colitis are the third-generation cephalosporin group – ampicillin, amoxicillin and clindamycin. The antimicrobials least likely to be associated with C difficile colitis include parenterally administered aminoglycosides and vancomyin, sulphonamides, and antimicrobial agents that lack antibacterial activity (ie, some antifungal, antiviral and antiparasitic antimicrobials). Among the broad spectrum agents, the third-generation cephalosporins, trovafloxacin (Trovan, Pfizer Canada Inc, Kirkland, Quebec), possibly ciprofloxacin (Cipro, Bayer Healthare Division, Toronto, Ontario) and clindamycin (Dalacin C, Pharmcia & Upjohn, Mississauga, Ontario) appear to have been implicated most frequently (8-10). For unknown reasons, other broad spectrum agents such as ticarcillin-clavulanate (Timentin, SmithKline Beecham, Oakville, Ontario) and piperacillin-tazobactam (Tazocin, StLaurent, Quebec) have been less frequently implicated. However, virtually all antibiotics have been associated with C difficile colitis.