During the last few years it has been documented by several investigators that Clostridium difficile intestinal colonization and toxin production can occur in both symptomatic and asymptomatic human infants. Preliminary experiments demonstrate that C. difficile asymptomatically colonizes the intestinal tracts of non-antibiotic treated hamsters between the ages of 4 and 13 days. On the other hand, the administration of clindamycin to hamsters 4 days of age or older consistently results in the development of C. difficile-associated ileocecitis. The overall objective of this proposal is to determine the mechanism(s) accounting for the differences in the toxicity of C difficile for clindamycin treated and non-antibiotic treated infant hansters. This objective will be accomplished by examining specific parameters associated with toxigenic C. difficile intestinal colonization in infant and adult hamsters, with and without prior clindamycin treatment. Parameters which will be examined include; strain variation in the toxicity of C. difficile to hamsters, site of C. difficile intestinal colonization and/or the site in the intestinal tract in which the toxins of C. difficile are produced, impact of clindamycin administration on the susceptibility of hamsters to C. difficile toxins A and B, presence of toxin neutralizing activity in the intestinal contents of hamsters, and the effect of clindamycin on C. difficile toxin production. The infant hamster model of C. difficile intestinal colonization may help delineate the mechanisms of C. difficile colonization of infant humans in the absence and presence of intestinal disease. In addition, this animal model may aid in our understanding of the pathogenesis of C. difficile-associated disease in adults as well as possible means of prevention and treatment.
