What is the treatment for Clostridioides difficile (C. diff) diarrhea?

Treatment of Clostridioides difficile (C. diff) Diarrhea

For C. difficile infection (CDI), oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the preferred first-line treatments, with metronidazole reserved only for mild-moderate initial episodes when access to vancomycin or fidaxomicin is limited. 1

Diagnosis and Classification

Before initiating treatment, proper diagnosis is essential:

• Test for C. difficile in patients with diarrhea (≥3 unformed stools in 24 hours)
• Nucleic acid amplification testing (NAAT) has high sensitivity (90-92%) and specificity (94-96%) 2
• Classify disease severity to guide treatment:
  • Mild-moderate CDI: Diarrhea without systemic signs, WBC <15,000 cells/mL, serum creatinine <1.5 times baseline
  • Severe CDI: Systemic signs of infection, WBC ≥15,000 cells/mL, or serum creatinine ≥1.5 times baseline
  • Fulminant CDI: Hypotension, shock, ileus, or megacolon

Initial Treatment Based on Severity

Mild-Moderate CDI

• First-line: Oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 2, 1
• Alternative (only if limited access to first-line): Oral metronidazole 500 mg three times daily for 10-14 days 2, 1

Severe CDI

• First-line: Oral vancomycin 125 mg four times daily for 10-14 days OR fidaxomicin 200 mg twice daily for 10 days 2, 1
• Metronidazole should NOT be used for severe cases

Fulminant CDI/Complicated CDI

• Oral vancomycin 500 mg four times daily PLUS
• Intravenous metronidazole 500 mg every 8 hours
• If ileus present: Add rectal vancomycin 500 mg in 500 mL saline as enema four times daily 2
• Consider surgical consultation for possible colectomy in severe cases

Management of Recurrent CDI

Recurrence occurs in approximately 20% of cases, with risk factors including:

• Age >65 years
• Concomitant antibiotic use
• Comorbidities
• Proton pump inhibitor use
• Initial disease severity 2

First Recurrence

• If metronidazole was used initially: Vancomycin 125 mg four times daily for 10 days 2, 1
• If vancomycin or fidaxomicin was used initially: Use fidaxomicin 200 mg twice daily for 10 days 1, 3

Second Recurrence

• Vancomycin oral taper and pulse 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
• OR fidaxomicin 200 mg twice daily for 10 days (if not used previously) 2, 3

Multiple Recurrences (≥3)

• Consider fecal microbiota transplantation (FMT) 2, 1
• FMT has shown high success rates (>90%) in resolving recurrent CDI 2

Additional Management Strategies

1. Discontinue the inciting antibiotic as soon as possible 1
2. Avoid anti-motility agents as they may mask symptoms and potentially worsen disease
3. Implement infection control measures:
   • Hand hygiene with soap and water (alcohol-based sanitizers are less effective against C. difficile spores)
   • Contact precautions and isolation
   • Thorough environmental cleaning 1
4. Monitor for clinical response during the first 5-6 days of treatment
   • Consider changing therapy if no improvement or clinical deterioration 1

Special Considerations

• Elderly patients: Monitor renal function during vancomycin treatment 1
• Prolonged metronidazole use: Avoid due to risk of cumulative and potentially irreversible neurotoxicity 1
• Fidaxomicin advantages: Lower recurrence rates compared to vancomycin (15.4% vs 25.3%) particularly for non-NAP1 strains 4
• Monitor for recurrence for up to 2 months after treatment 1

Treatment Algorithm Summary

1. Confirm diagnosis with appropriate testing
2. Assess severity of infection
3. Select appropriate initial therapy based on severity
4. Monitor response to treatment
5. Manage recurrences with appropriate escalation of therapy
6. Consider FMT for multiple recurrences

The evidence strongly supports vancomycin or fidaxomicin as first-line agents for CDI, with treatment selection guided by disease severity, recurrence status, and patient-specific factors.