Treatment of Recurrent Clostridioides difficile Infection

Introduction to Management

The American College of Gastroenterology recommends treating the first recurrence of C. difficile infection with oral vancomycin 125 mg four times daily for 10-14 days or fidaxomicin 200 mg twice daily for 10 days, with moderate quality evidence supporting the superiority of vancomycin over metronidazole for sustained response 1, 2, 3
For second and subsequent recurrences, the American College of Gastroenterology suggests using either vancomycin tapered/pulsed regimen or proceeding directly to fecal microbiota transplantation (FMT), which achieves 87-92% clinical resolution 1, 2, 3

The Infectious Diseases Society of America recommends treating the first recurrence identically to the initial episode unless disease has progressed from non-severe to severe, with moderate quality evidence supporting this approach 4, 1, 3
Oral vancomycin 125 mg four times daily for 10-14 days is the preferred first-line option, with moderate quality evidence supporting its superiority over metronidazole for sustained response 1, 2, 3
Fidaxomicin 200 mg twice daily for 10 days is an excellent alternative, particularly for patients at high risk for subsequent recurrence, as it reduces recurrence rates to 19.7% compared to 35.5% with standard vancomycin 2, 3

The American College of Gastroenterology recommends vancomycin tapered and pulsed regimen as the most evidence-supported antibiotic approach for patients with multiple recurrences, with a regimen of vancomycin 125 mg every 6 hours for 10-14 days, then 125 mg every 12 hours for 7 days, then 125 mg every 24 hours for 7 days, then 125 mg every 48-72 hours for 2-8 weeks 4, 5, 2, 3
Fecal microbiota transplantation (FMT) should be offered after at least 2 recurrences in patients who have failed appropriate antibiotic treatments, with strong recommendation and moderate to high quality evidence 6, 1, 2, 3
FMT demonstrates superior outcomes with clinical resolution rates of 87-92% compared to 40-50% with antibiotics alone 2, 3

The Society for Healthcare Epidemiology of America recommends considering adding bezlotoxumab (monoclonal antibody against C. difficile toxin B) 10 mg/kg as a single intravenous infusion over 60 minutes to standard antibiotic therapy for patients at high risk of recurrence, particularly those with severe CDI presentation 3

The Centers for Disease Control and Prevention recommends discontinuing all inciting antibiotics immediately if clinically possible, as continued antibiotic use is the strongest predictor of treatment failure and recurrence 1, 2, 3
Discontinue proton pump inhibitors if not absolutely required, as they are associated with increased CDI recurrence risk 2, 3
Implement strict handwashing with soap and water and isolate patients until resolution of diarrhea (formed stool for at least 48 hours) 1

The American College of Surgeons recommends watching for warning signs requiring escalation, including WBC ≥15,000-25,000 cells/mL or rising, serum lactate ≥5.0 mmol/L, ileus, toxic megacolon, peritoneal signs, or hemodynamic instability 1, 2, 3
Obtain prompt surgical consultation if perforation, toxic megacolon, severe ileus, lactate >5.0 mmol/L, or systemic inflammation with deteriorating clinical condition despite antibiotic therapy develops 1, 3

The American Gastroenterological Association recommends not performing "test of cure" after CDI treatment, as C. difficile can persist asymptomatically and testing does not predict clinical outcomes 7
Do not use intravenous vancomycin for CDI, as it is not excreted into the colon and has no efficacy against CDI 3
Do not delay FMT in multiply recurrent cases waiting for additional antibiotic courses, as each recurrence increases risk of subsequent recurrence and FMT has superior efficacy 6, 2, 3