Effect of the synthetic bile salt analog CamSA on the hamster model of Clostridium difficile infection.

Effect of the synthetic bile salt analog CamSA on the hamster model of Clostridium difficile infection. Antimicrob Agents Chemother. 2018 Jul 16;: Authors: Howerton A, Seymour CO, Murugapiran SK, Liao Z, Phan JR, Estrada A, Wagner AJ, Mefferd CC, Hedlund BP, Abel-Santos E Abstract Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and has gained worldwide notoriety due to emerging hypervirulent strains and high incidence of recurrence. We previously reported protection of mice from CDI using the anti-germinant bile salt analog CamSA. Here we describe the effects of CamSA on the hamster model of CDI. CamSA treatment of hamsters showed no toxicity and did not affect the richness or diversity of gut microbiota; however, minor changes in community composition were observed. Treatment of C. difficile-challenged hamsters with CamSA doubled the mean time to death compared to control hamsters. However, CamSA alone was insufficient to prevent CDI in hamsters. CamSA in conjunction with suboptimal concentrations of vancomycin led to complete protection from CDI in 70% of animals. Protected animals remained disease-free at least 30 days post-challenge and showed no signs of colonic tissue damage. In a delayed treatment model of hamster CDI, CamSA was unable to prevent infection signs and mortality. These data support a putative model where CamSA reduces the number of germinating C. difficile spores but d...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research