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A new strategy for the prevention of Clostridium difficile infection.
J Infect Dis. 2013 May 15; 207(10):1498-504.JI

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+Show Affiliations

Department of Chemistry, University of Nevada, Las Vegas, NV 89154, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23420906

Citation

Howerton, Amber, et al. "A New Strategy for the Prevention of Clostridium Difficile Infection." The Journal of Infectious Diseases, vol. 207, no. 10, 2013, pp. 1498-504.
Howerton A, Patra M, Abel-Santos E. A new strategy for the prevention of Clostridium difficile infection. J Infect Dis. 2013;207(10):1498-504.
Howerton, A., Patra, M., & Abel-Santos, E. (2013). A new strategy for the prevention of Clostridium difficile infection. The Journal of Infectious Diseases, 207(10), 1498-504. https://doi.org/10.1093/infdis/jit068
Howerton A, Patra M, Abel-Santos E. A New Strategy for the Prevention of Clostridium Difficile Infection. J Infect Dis. 2013 May 15;207(10):1498-504. PubMed PMID: 23420906.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new strategy for the prevention of Clostridium difficile infection. AU - Howerton,Amber, AU - Patra,Manomita, AU - Abel-Santos,Ernesto, Y1 - 2013/02/18/ PY - 2013/2/20/entrez PY - 2013/2/20/pubmed PY - 2013/6/12/medline SP - 1498 EP - 504 JF - The Journal of infectious diseases JO - J. Infect. Dis. VL - 207 IS - 10 N2 - 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. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/23420906/A_new_strategy_for_the_prevention_of_Clostridium_difficile_infection_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jit068 DB - PRIME DP - Unbound Medicine ER -