What is the best treatment approach for a patient experiencing a recurrence of Clostridioides difficile (C. diff) infection?

Treatment of Recurrent Clostridioides difficile Infection

Fidaxomicin should be preferred over vancomycin for patients experiencing a first recurrence of C. difficile infection due to its superior sustained response rates and lower recurrence risk. 1

First Recurrence Treatment Algorithm

Preferred Treatment Options

1. Fidaxomicin 200 mg twice daily for 10 days

   • Provides 27% higher sustained response compared to vancomycin at 30 days post-treatment 1
   • Reduces recurrence rates (19.7% vs 35.5% with vancomycin) 1
   • Consider extended-pulsed regimen (days 1-5: 200 mg twice daily, days 6-25: 200 mg once every other day) for even lower recurrence rates 1

2. Vancomycin 125 mg four times daily for 10 days (if fidaxomicin unavailable/contraindicated)

   • Standard alternative when fidaxomicin is not an option 1
   • Consider tapered/pulsed regimen for patients with multiple risk factors for recurrence 2

Risk Stratification for Treatment Selection

Factors indicating higher risk for subsequent recurrences:

• Age ≥65 years
• History of multiple CDI episodes
• Immunocompromised status
• Severe CDI at presentation
• Infection with hypervirulent strain (ribotype 027)
• Frailty (Clinical Frailty Scale ≥4) 3
• Short interval between recurrences (<17 days) 3

Second or Subsequent Recurrences

For patients with ≥2 recurrences, consider:

1. Fecal Microbiota Transplantation (FMT)

   • Strongly recommended after two or more recurrences 1
   • Also indicated for patients with one recurrence who have risk factors for further episodes 1
   • Success rates of 80-90% in preventing further recurrences 1

2. Vancomycin in tapered and pulsed regimen

   • 125 mg four times daily for 10-14 days, then
   • 125 mg twice daily for 7 days, then
   • 125 mg once daily for 7 days, then
   • 125 mg every 2-3 days for 2-8 weeks 2

3. Bezlotoxumab (adjunctive therapy)

   • Single 10 mg/kg IV infusion given with antibiotic treatment
   • Reduces recurrence rates by approximately 40% compared to standard treatment alone 4
   • Most beneficial for patients with multiple risk factors for recurrence 4

Treatment Considerations and Caveats

Efficacy Evidence

• Fidaxomicin shows superior sustained response at 30 days post-treatment compared to vancomycin (RR: 1.27; 95% CI: 1.05-1.54) 1
• The benefit of fidaxomicin is more pronounced in patients with first recurrence (RR: 1.23; 95% CI: 1.01-1.49) 1
• Extended-pulsed fidaxomicin regimen showed remarkably low recurrence rates (2% vs 17% with standard vancomycin) 1

Common Pitfalls to Avoid

1. Using metronidazole for recurrent CDI

   • Not recommended due to lower efficacy and risk of neurotoxicity with prolonged use, especially in patients with liver disease 1

2. Failing to discontinue other antibiotics

   • Continued use of non-CDI antibiotics significantly increases risk of treatment failure and further recurrences 2

3. Delaying FMT consideration

   • Should be offered after two recurrences or after one recurrence with risk factors for further episodes 1

4. Repeating stool testing too early

   • Test of cure is not recommended as C. difficile or its toxins may persist in stool after clinical resolution 2

5. Overlooking bezlotoxumab for high-risk patients

   • Consider adding to antibiotic therapy for patients with multiple risk factors for recurrence 4

Special Populations

• Severe or complicated CDI: Higher doses of vancomycin (up to 500 mg four times daily) may be needed 2
• Ileus or toxic megacolon: Consider adding rectal vancomycin (500 mg in 100 mL normal saline four times daily) 2
• Immunocompromised patients: Higher risk of recurrence; consider early use of fidaxomicin or bezlotoxumab 4

By following this evidence-based approach to recurrent C. difficile infection, clinicians can maximize treatment success and minimize the risk of further recurrences, thereby reducing morbidity, mortality, and improving quality of life for patients with this challenging condition.