Co-infection of hamsters with toxin A or toxin B-deficient Clostridium difficile strains

Male Syrian hamsters (Mesocricetus auratus) were used to study interactions between different toxin deficient strains of C. difficile. After sensitization with clindamycin, hamsters were intragastrically co-infected with the appropriate dilutions corresponding to 100, 1000 and 10,000 cells of four (toxin A or B-deficient) C. difficile strains (8864, P-829, W-38 and W-74). In addition, a group of hamsters was infected with C. difficile VPI 10463, a reference toxigenic strain. Colonization and mortality was observed within 48 hours in the group of hamsters infected with the reference toxigenic strain. No clinical disease was observed in the groups of hamsters co-infected with the toxin A or B-deficient strains. Re-infection of these hamsters (co-infected with toxin deficient isolates) with C. difficile VPI 10463 resulted in clinical disease and death suggesting that these strains do not confer protection against infection with a toxigenic strain. Macroscopic and microscopic observations of the cecum of re-infected hamsters demonstrated uniformly multiple large hemorrhagic areas without pseudomembranes. Hamsters infected with as few as 100-500 cells of the toxigenic strain--VPI 10463 alone demonstrated pseudomembranes and multiple hemorrhages. These results suggest that even though the toxin deficient strains did not prevent re-infection with a toxigenic strain of C. difficile, they may play a role in the histopathologic changes after re-infections in the hamster model. Further studies with a larger number of hamsters and C. difficile strains of various molecular profiles are required to better understand the interaction between these strains.