Colonization for the prevention of Clostridium difficile disease

The most successful methods to control Clostridium difficile-associated dis ease (CDAD) have been the institution of barrier precautions (isolation, go wns, gloves) and the restriction of antimicrobial agent use, particularly c lindamycin. Experiments with hamsters published in the 1980s suggested that colonization of the gastrointestinal tract with non-toxigenic C. difficile prevented disease from orally administered toxigenic C. difficile strains, although the prevention was only partial and limited in duration. More rec ently, observational studies of hospitalized humans have shown that patient s who have primary asymptomatic stool colonization with C, difficile are at significantly lower risk of CDAD when compared to patients in the same hos pital environment at the same time who are not colonized with C. difficile (P=0.021). When analysis was confined to only patients who had received ant ibiotics within the previous 2-3 weeks, the CDAD rate was also significantl y lower in the C. difficile colonized patients (P=0.024). The most frequent ly isolated non-toxigenic C. difficile strains found in colonized humans ha ve been used in the hamster model to prevent fatal CDAD. These strains were found to successfully colonize 90-100% of hamsters for 35 to 90 days when given as a single oral dose two days after clindamycin. Challenge orally wi th 100 cfu of spores of toxigenic C. difficile at 5 days post clindamycin i s 100% fatal at 48 h unprotected hamsters, but prevention of CDAD occurred in 100% of hamsters previously colonized with non toxigenic C. difficile. S uccessful, safe, and durable colonization of human volunteers will be requi red before clinical trials of non-toxigenic C. difficile can begin in patie nts, but this approach shows promise in both animal studies and observation s in humans. (C) 1999 Academic Press.