Enterotoxic Clostridia: Clostridioides difficile Infections

Clostridioides difficile is a Gram-positive, anaerobic, spore forming pathogen of both humans and animals and is the most common identifiable infectious agent of nosocomial antibiotic-associated diarrhea. Infection can occur following the ingestion and germination of spores, often concurrently with a disruption to the gastrointestinal microbiota, with the resulting disease presenting as a spectrum, ranging from mild and self-limiting diarrhea to severe diarrhea that may progress to life-threating syndromes that include toxic megacolon and pseudomembranous colitis. Disease is induced through the activity of the C. difficile toxins TcdA and TcdB, both of which disrupt the Rho family of GTPases in host cells, causing cell rounding and death and leading to fluid loss and diarrhea. These toxins, despite their functional and structural similarity, do not contribute to disease equally. C. difficile infection (CDI) is made more complex by a high level of strain diversity and the emergence of epidemic strains, including ribotype 027-strains which induce more severe disease in patients. With the changing epidemiology of CDI, our understanding of C. difficile disease, diagnosis, and pathogenesis continues to evolve. This article provides an overview of the current diagnostic tests available for CDI, strain typing, the major toxins C. difficile produces and their mode of action, the host immune response to each toxin and during infection, animal models of disease, and the current treatment and prevention strategies for CDI.