2 Toxin production: C. difficile produces two toxins, designated toxin A and toxin B.⁵ Early studies implicated toxin A as the major cause of enteric toxin based on animal studies that showed florid colitis with injection of toxin A into bowel loops, but more recent studies establish that toxin B is critical for clinical expression.⁵ Most strains of C. difficile produce both toxins, but about 1% to 2% produce only toxin B.⁶

3 Antibiotic exposure: this is the most important identifiable risk and presumably reflects the impact of the inducing agent on the colonic flora, establishing the opportunity for C. difficile to convert from the spore form to the vegetative form, with replication and toxin production. Virtually every antibiotic with an antibacterial spectrum has been implicated, but the most frequent are clindamycin and broad-spectrum cephalosporins. In current practice, fluoroquinolones account for the majority of cases, presumably reflecting their enormous usage rates.⁴ Particularly important in recent years is the NAP-1 strain which is associated with fluoroquinolone use (see 5 below).

4 Epidemiology: C. difficile is relatively infrequent in ambulatory persons, but rates of colonization and disease are much higher as a result of exposure to the hospital environment.³ C. difficile now represents an important and potentially lethal nosocomial pathogen. Nursing homes are another setting in which there is clustering of vulnerable patients with high rates of antibiotic use where C. difficile may be endemic or epidemic.⁶ In the period 2001-2006, the NAP-1 strain emerged as an important epidemic agent of C. difficile in Canada, the United States, and Europe.^4,6 This strain appears to be particularly virulent, with increased toxin production, mortality, treatment failure, and relapses.