Antigermination therapy prevented disease in mice challenged with massive inocula of C. difficile spores.

Spore germination is necessary for the development of symptomatic Clostridium difficile infection (CDI). Recent investigations have yielded novel nonantibiotic agents that inhibit spore germination mediated by taurocholate, a bile salt. To determine whether CamSA — a taurocholate analog that inhibits germination in vitro — might prevent CDIs, researchers conducted experiments using a mouse model.

Mice received an antibiotic “cocktail” in their drinking water for 3 days, and then a single dose of intraperitoneally administered clindamycin on day 4. The animals, in groups of five, each received 0 mg/kg, 5 mg/kg, 25 mg/kg, or 50 mg/kg of CamSA by oral gavage, followed on day 5 by gavage challenge with a massive dose of C. difficile spores and additional doses of CamSA 1 and 24 hours thereafter. The mice were then monitored for clinical evidence of CDI, and disease signs were scored. Some animals in each group were sacrificed and underwent postmortem examination of the gastrointestinal tract.

All animals that received 0 mg/kg of CamSA developed severe CDI within 48 hours of spore inoculation. In contrast, those that received 50 mg/kg showed no clinical or histopathologic evidence of CDI. Animals that received either 5 mg/kg or 25 mg/kg had a delayed onset of CDI and a reduction in disease severity. The excretion of cells and spores in feces also correlated with CamSA dose: Vegetative cells predominated in animals in the untreated (0-mg/kg) and 5-mg/kg groups, whereas spores predominated in those in the 25-mg/kg and 50-mg/kg groups.

Although CamSA (3 doses at 50 mg/kg) was protective in mice challenged with spores, it was ineffective in preventing CDI in animals challenged with vegetative cells.

Comment: These findings in a murine model deserve special attention. The novel, nonantibiotic strategy studied could be a “game changer” as we consider potential approaches for CDI management. As the authors note, patients determined to be at risk for CDI could receive CamSA before initiating antibiotics, then additional doses as needed until the intestinal microbiota has recovered.

Source: Journal Watch Infectious Diseases