Extraintestinal Manifestations of Clostridioides difficile Infections: An Overview

This article systematically summarizes potential extraintestinal manifestations of Clostridioides difficile infection, including infectious and non-infectious complications, providing critical clinical references for early recognition and management. The study presents comprehensive data and in-depth mechanistic analysis, offering significant guidance for diagnosing and treating patients with immunosuppression or intestinal barrier damage.

 

Literature Overview
This article published in Antibiotics, titled 'Extraintestinal Manifestations of Clostridioides difficile Infections: An Overview', reviews and summarizes extraintestinal manifestations of Clostridioides difficile infections, including infectious complications and non-infectious presentations. It analyzes potential pathogenic mechanisms and clinical characteristics, emphasizing that extraintestinal infections may occur through hematogenous dissemination or direct contamination in immunosuppressed patients or those with intestinal barrier damage, which has significant clinical implications for diagnosis and treatment.

Background Knowledge
Clostridioides difficile (C. difficile) is a Gram-positive, toxin-producing anaerobic bacterium primarily causing pseudomembranous colitis and antibiotic-associated diarrhea. Recent reports increasingly describe extraintestinal manifestations of C. difficile infection, including bacteremia, intra-abdominal infections, central nervous system involvement, and musculoskeletal infections. Although the incidence rate remains below 1%, these manifestations pose significant clinical challenges due to their association with high mortality. This review analyzes potential mechanisms, clinical features, and treatment strategies for extraintestinal C. difficile infections, offering clinical guidance and research directions for healthcare professionals.

 

 

Research Methods and Experiments
A systematic literature search was conducted using PubMed, Embase, and ResearchGate databases up to February 15, 2025, with search terms including 'extraintestinal manifestations', 'extraintestinal infections', and 'Clostridioides difficile'. The study reviewed case reports and clinical studies on extraintestinal complications of C. difficile infection, analyzing associated risk factors, clinical features, and treatment responses.

Key Conclusions and Perspectives

• Extraintestinal manifestations of C. difficile infection occur in less than 1% of cases, primarily presenting as bacteremia, intra-abdominal/pelvic abscesses, and rare non-infectious complications such as reactive arthritis.
• Major risk factors include immunosuppression, intestinal barrier disruption (e.g., colitis, surgery, perforation), antibiotic exposure, advanced age, and hospitalization history.
• Extraintestinal infections typically occur through translocation of bacteria/toxins into the bloodstream after intestinal barrier damage, or direct contamination during surgical/traumatic events.
• Bacteremia is often polymicrobial but can present as monomicrobial infections, with mortality rates reaching 20-40%, highlighting the importance of early identification and intervention.
• Intra-abdominal infections most commonly involve splenic or hepatic abscesses, typically resulting from hematogenous dissemination and presenting with fever and elevated inflammatory markers.
• Central nervous system infections are rare but may occur through direct inoculation during procedures. Some cases lack intestinal symptoms, necessitating high clinical suspicion.
• Musculoskeletal infections frequently occur in patients with prosthetic joints, often caused by surgical contamination. Blood cultures are commonly negative, requiring tissue or joint fluid cultures for diagnosis.
• Soft tissue infections and surgical site infections are associated with environmental contamination, with some strains differing from intestinal isolates, indicating hospital-acquired transmission.
• Cardiovascular infections (e.g., infectious aneurysms, pericarditis) may originate from hematogenous dissemination or surgical contamination, requiring combined surgical and antibiotic management.
• Non-infectious manifestations primarily include reactive arthritis, occurring approximately 10 days post-infection and associated with HLA-B27 antigen, typically managed with non-steroidal anti-inflammatory drugs.

Research Significance and Prospects
This article provides a systematic synthesis of clinical features and pathogenic mechanisms of extraintestinal C. difficile infections, emphasizing the necessity for clinicians to consider extraintestinal presentations in high-risk patients. Future research should focus on host-pathogen interactions involving C. difficile toxins, and explore optimized diagnostic and therapeutic strategies.

 

 

Conclusion
While C. difficile infection primarily affects the gastrointestinal tract, its extraintestinal manifestations have significant clinical importance, particularly in immunosuppressed or intestinal barrier-compromised patients. These include bacteremia, intra-abdominal infections, central nervous system involvement, musculoskeletal infections, and cardiovascular complications, along with non-infectious manifestations like reactive arthritis. This review synthesizes current literature to characterize pathogenic mechanisms, clinical features, and management strategies, underscoring the importance of early recognition and multidisciplinary care. Future studies should investigate the roles of toxins A/B and their variants in extraintestinal pathogenesis, and explore host immune susceptibility factors to improve diagnostic and therapeutic approaches.

 

Konstantinos Mpakogiannis, Fotios S Fousekis, Stylianos Elemes, Eirini Christaki, and Konstantinos H Katsanos. Extraintestinal Manifestations of Clostridioides difficile Infections: An Overview. Antibiotics.