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Clostridioides difficile infection — Clinical Guidelines

Overview

Clostridioides difficile infection (CDI) is a common healthcare-associated infection characterized by diarrhea and can range from mild to severe, including toxic megacolon. Recurrent CDI (rCDI) poses significant therapeutic challenges and often requires advanced interventions like fecal microbiota transplantation (FMT). 1 2 5

Diagnosis

Key Diagnostic Criteria: Presence of diarrhea, typically ≥3 unformed stools/day, in conjunction with a positive C. difficile toxin test or nucleic acid amplification test (NAAT). 8

Recommended Tests: Toxin testing (either alone or as part of a multistep algorithm) or NAAT; NAAT alone is commonly used without toxin testing in many institutions. 8

Grading: No specific grading system mentioned for diagnostic criteria, but accurate testing methods are crucial for reliable diagnosis. 8

Management

First-Line Treatments:

- Antibiotics: Vancomycin (typically 125 mg orally four times daily for 10 days) and fidaxomicin are recommended for initial treatment of CDI. 5 - Bezlotoxumab: Consideration for use in patients at high risk of recurrence, typically in combination with antibiotics. 5

Adjunctive Treatments:

- Fecal Microbiota Transplantation (FMT): Recommended for recurrent or refractory CDI when standard antibiotic therapies fail. 1 2 3 - Extended Duration of Antibiotic Therapy: No significant difference in recurrence rates noted with prolonged versus standard duration of CDI treatment or extended versus non-extended antibiotic cessation periods. 4

Special Populations

Pediatrics: Diagnostic testing practices vary; NAAT without toxin testing is common, but testing in infants and young children is not universally restricted. 8

Elderly and Comorbidities: Specific guidelines highlight the importance of donor screening and FMT safety, particularly relevant in immunocompromised or elderly patients. 1 2 3

Key Recommendations

Use FMT for Recurrent or Refractory CDI: Select use of fecal microbiota-based therapies, including FMT, in immunocompetent adults with recurrent CDI (Evidence: Strong) 3

Consider Bezlotoxumab in High-Risk Patients: For adults with recurrent CDI, consider bezlotoxumab in conjunction with antibiotics to reduce recurrence risk (Evidence: Moderate) 5

Maintain Rigorous Donor Screening: Ensure stringent donor screening protocols to prevent pathogen transmission, especially in the context of pandemics like COVID-19 (Evidence: Expert opinion) 1 2

References

1 Prati D, Caprioli F, Stea L, Berzuini A, Pizzotti D, Petrillo E et al.. A "movement" worth making: why and how Transfusion Services can play a role in Fecal Microbiota Transplant programs. Blood transfusion = Trasfusione del sangue 2025. link 2 Mullish BH, Merrick B, Quraishi MN, Bak A, Green CA, Moore DJ et al.. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. The Journal of hospital infection 2024. link 3 Peery AF, Kelly CR, Kao D, Vaughn BP, Lebwohl B, Singh S et al.. AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases. Gastroenterology 2024. link 4 Keats KR, Stitt TM, Chastain DB, Jivan BP, Matznick E, Waller JL et al.. Evaluating . Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners 2022. link 5 Johnson S, Lavergne V, Skinner AM, Gonzales-Luna AJ, Garey KW, Kelly CP et al.. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2021. link 6 Shaffer SR, Nugent Z, Walkty A, Yu BN, Lix LM, Targownik LE et al.. Time trends and predictors of laboratory-confirmed recurrent and severe . CMAJ open 2020. link 7 Ianiro G, Bibbò S, Masucci L, Quaranta G, Porcari S, Settanni CR et al.. Maintaining standard volumes, efficacy and safety, of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2020. link 8 Kociolek LK, Kutty PK, Polgreen PM, Beekmann SE. Healthcare provider diagnostic testing practices for identification of Clostridioides (Clostridium) difficile in children: an Emerging Infections Network survey. Infection control and hospital epidemiology 2019. link

Clostridioides difficile infection