title: A new strategy for the prevention of Clostridium difficile infection.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) is a leading cause of antibiotic-associated diarrhea. The infective form of C. difficile is the spore, but the vegetative bacterium causes the disease. Because C. difficile spore germination is required for symptomatic infection, antigermination approaches could lead to the prevention of CDI. We recently reported that CamSA, a bile salt analog, inhibits C. difficile spore germination in vitro.
  
  
  METHODS
  Mice infected with massive inocula of C. difficile spores were treated with different concentrations of CamSA and monitored for CDI signs. C. difficile spore and vegetative cells were counted in feces from infected mice.
  
  
  RESULTS
  A single 50-mg/kg dose of CamSA prevented CDI in mice without any observable toxicity. Lower CamSA doses resulted in delayed CDI onset and less severe signs of disease. Ingested C. difficile spores were quantitatively recovered from feces of CamSA-protected mice.
  
  
  CONCLUSIONS
  Our results support a mechanism whereby the antigermination effect of CamSA is responsible for preventing CDI signs. This approach represents a new paradigm in CDI treatment. Instead of further compromising the microbiota of CDI patients with strong antibiotics, antigermination therapy could serve as a microbiota surrogate to curtail C. difficile colonization of antibiotic-treated patients.
authors: Department of Chemistry, University of Nevada, Las Vegas, NV 89154, USA.
authors: Amber
authors: A
authors: Howerton
authors: Manomita
authors: M
authors: Patra
authors: Ernesto
authors: E
authors: Abel-Santos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000494:pharmacology; D016360:Clostridioides difficile / Q000187:drug effects* / Q000472:pathogenicity; D003015:Clostridium Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D003091:Colistin / Q000494:pharmacology; D003967:Diarrhea / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000382:microbiology; D005260:Female; D005839:Gentamicins / Q000494:pharmacology; D007612:Kanamycin / Q000494:pharmacology; D054892:Metagenome; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D013171:Spores, Bacterial / Q000187:drug effects / Q000472:pathogenicity; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D005839:Gentamicins; D008795:Metronidazole; D007612:Kanamycin; D014640:Vancomycin; D003091:Colistin