Abstract
INTRODUCTION: Clostridioides difficile (C. difficile) is primarily associated with colonic disease, including pseudomembranous colitis. However, in rare instances, it may cause extraintestinal infectious and non-infectious manifestations, particularly in immunocompromised patients or those with significant underlying conditions. SEARCH METHODS: A literature review was performed using PubMed, Embase, and Researchgate databases up to 15 February 2025. The following search strings were used: "extraintestinal manifestations", "extracolonic manifestations", "extraintestinal infections", "extracolonic infections", "Clostridium difficile", and "Clostridioides difficile". RESULTS: Extraintestinal manifestations of C. difficile appear to represent fewer than 1% of all reported infections. The most frequently reported infectious complications include bacteremia and abdominopelvic infections and abscesses, often involving polymicrobial cultures, with the isolation of C. difficile alongside microorganisms typically found in the normal intestinal microbiota. Rare non-infectious cases, such as reactive arthritis, have also been described. The underlying pathogenetic mechanism is believed to involve disruption of the intestinal barrier and translocation of bacteria or toxins to sterile sites. CONCLUSIONS: Though rare, extraintestinal C. difficile manifestations pose important clinical challenges. Better understanding of their mechanisms is essential for early recognition and appropriate management. Further research is warranted to define potential mechanisms and therapeutic approaches.