Grant: Operating Grant: Industry-partnered Collaborative Research - Other Partner

C. difficile causes a condition now called C. difficile infection(CDI) in hospitalized patients. This occurs when hospital patients are treated with antibiotics in order to prevent opportunistic infections. In some cases, however, eradicating the normal gut microflora (NF) with antibiotics leaves the GI tract of these subjects vulnerable to colonization by C. difficile. Once these organisms, which display an inherent resistance to many common antibiotics, gain a foothold, they produce two high molecular weight exotoxins (TcdA and TcdB) which are primarily responsible for the clinical symptoms associated with these infections. In many cases, the condition can be successfully treated by replacing the offending antibiotic with one, typically metronidazole, to which C. difficile is sensitive. In approximately 20% of cases, however, the condition will return once the antibiotics are withdrawn and it is only a matter of time before multi-drug resistant C. difficile strains begin to appear in hospitals. The hypothesis to be tested is that toxins and adherence to host intestinal cells both contribute to CDI pathogenesis and, as a consequence, anti-infective agents designed to neutralize C. difficile toxins as well as inhibit C. difficile colonization of the GI tract will provide greater therapeutic benefit in subjects suffering from this infectious condition. The proposal is to assess, in vitro and in vivo, the potential therapeutic benefit of using C. difficile-specific egg yolk antibodies (IgY) to inhibit colonization of the GI tract by these organisms.