Prevention of Fatal Clostridium difficile-Associated Disease during Continuous Administration of Clindamycin in Hamsters

Abstract

Clostridium difficile-associated disease (CDAD) due to toxigenic strains is prevented in hamsters by colonization by nontoxigenic C. difficile after administration of clindamycin (Cm). To prevent CDAD during treatment with antibiotics, we gave a Cm-resistant nontoxigenic C. difficile strain, M13 (minimal inhibitory concentration [MIC], >256 μg/mL), and a Cm-susceptible strain, M3 (MIC, 0.5 μg/mL), to hamsters receiving Cm daily for days 1-5. Either M13 or M3 was given orogastrically (1 × 10 6 spores/day) to each hamster in 3 groups of 5 each, on either day 3, days 3-5, or days 3-7. M13 colonized at a higher rate and faster than did M3 (P < .001). When hamsters were challenged by toxigenic strain B1 on days 5, 7, or 9, M13 prevented CDAD in 100% of the hamsters. M3 protected no hamsters challenged by B1 on day 5, 20% on day 7, and 100% on day 9. M13 contains the erm(B) resistance gene but not the mobilizable element Tn5398. The benefits of use of Cm-resistant nontoxigenic C. difficile to prevent CDAD must be balanced against the risk that resistance might be transferred to other enteric bacteria.