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dc.contributor.authorLi, Yuesheng
dc.contributor.authorFigler, Robert A
dc.contributor.authorKolling, Glynis
dc.contributor.authorBracken, Tara C
dc.contributor.authorRieger, Jayson
dc.contributor.authorStevenson, Ralph W
dc.contributor.authorLinden, Joel
dc.contributor.authorGuerrant, Richard L
dc.contributor.authorWarren, Cirle A
dc.date.accessioned2013-06-12T14:48:54Z
dc.date.available2013-06-12T14:48:54Z
dc.date.issued2012-12-10
dc.identifier.citationBMC Infectious Diseases. 2012 Dec 10;12(1):342
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2334-12-342
dc.identifier.urihttp://hdl.handle.net/10724/19558
dc.description.abstractAbstract Background Activation of the A2A adenosine receptor (A2AAR) decreases production of inflammatory cytokines, prevents C. difficile toxin A-induced enteritis and, in combination with antibiotics, increases survival from sepsis in mice. We investigated whether A2AAR activation improves and A2AAR deletion worsens outcomes in a murine model of C. difficile (strain VPI10463) infection (CDI). Methods C57BL/6 mice were pretreated with an antibiotic cocktail prior to infection and then treated with vancomycin with or without an A2AAR agonist. A2AAR-/- and littermate wild-type (WT) mice were similarly infected, and IFNγ and TNFα were measured at peak of and recovery from infection. Results Infected, untreated mice rapidly lost weight, developed diarrhea, and had mortality rates of 50-60%. Infected mice treated with vancomycin had less weight loss and diarrhea during antibiotic treatment but mortality increased to near 100% after discontinuation of antibiotics. Infected mice treated with both vancomycin and an A2AAR agonist, either ATL370 or ATL1222, had minimal weight loss and better long-term survival than mice treated with vancomycin alone. A2AAR KO mice were more susceptible than WT mice to death from CDI. Increases in cecal IFNγ and blood TNFα were pronounced in the absence of A2AARs. Conclusion In a murine model of CDI, vancomycin treatment resulted in reduced weight loss and diarrhea during acute infection, but high recurrence and late-onset death, with overall mortality being worse than untreated infected controls. The administration of vancomycin plus an A2AAR agonist reduced inflammation and improved survival rates, suggesting a possible benefit of A2AAR agonists in the management of CDI to prevent recurrent disease.
dc.titleAdenosine A2A receptor activation reduces recurrence and mortality from Clostridium difficile infection in mice following vancomycin treatment
dc.typeJournal Article
dc.date.updated2013-06-07T13:18:13Z
dc.description.versionPeer Reviewed
dc.language.rfc3066en
dc.rights.holderYuesheng Li et al.; licensee BioMed Central Ltd.


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