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

Treatment of Clostridioides difficile Infection

For C. difficile infection (CDI), oral vancomycin or fidaxomicin is the preferred first-line treatment, with therapy selection based on disease severity, recurrence risk, and availability, while metronidazole should only be used for non-severe cases when other options are unavailable. 1

Treatment Algorithm Based on Disease Severity

Initial Episode

• Non-severe CDI:

  • First choice: Oral vancomycin 125 mg four times daily for 10 days 1
  • Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 2
  • When above options unavailable: Oral metronidazole 500 mg three times daily for 10 days 1

• Severe CDI: (WBC >15,000 cells/mL, serum creatinine >1.5 mg/dL, or clinical signs of severe colitis)

  • Oral vancomycin 125 mg four times daily for 10 days 3, 1
  • Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 2

• Fulminant CDI: (hypotension, shock, ileus, or megacolon)

  • Oral vancomycin 500 mg four times daily plus IV metronidazole 500 mg every 8 hours 3, 1
  • If ileus present: Add rectal vancomycin (500 mg in 100 mL normal saline as retention enema) 3
  • Consider surgical evaluation for possible colectomy if no improvement within 24-48 hours 4

Recurrent Episodes

• First recurrence:

  • Fidaxomicin 200 mg twice daily for 10 days (preferred if not used for initial episode) 2, 5
  • Vancomycin 125 mg four times daily for 10 days 1
  • Consider adding bezlotoxumab to standard treatment if high risk for further recurrence 5

• Second or subsequent recurrences:

  • Vancomycin extended/tapered regimen: 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks 3, 1
  • Fidaxomicin 200 mg twice daily for 10 days (if not previously used) 2
  • Consider fecal microbiota transplantation (FMT) after appropriate antibiotic lead-in 3, 4, 6

Important Management Principles

1. Discontinue the inciting antibiotic as soon as possible 3, 1

2. Avoid anti-peristaltic agents which may mask symptoms and potentially worsen disease 1

3. Implement infection control measures:

   • Contact precautions
   • Hand hygiene with soap and water (more effective than alcohol-based sanitizers) 1

4. Monitor for complications:

   • Toxic megacolon
   • Perforation
   • Sepsis
   • Severe ileus 1, 4

5. Ensure adequate fluid and electrolyte replacement 1

Special Considerations

• Diagnostic testing: Only test symptomatic patients with ≥3 unformed stools in 24 hours without laxative use 1, 7

• Pediatric patients: Treatment follows similar principles but with weight-based dosing:

  • Vancomycin: 10 mg/kg/dose (max 125 mg) four times daily
  • Metronidazole: 7.5 mg/kg/dose (max 500 mg) three times daily 3

• When oral therapy not possible:

  • IV metronidazole 500 mg every 8 hours
  • Consider rectal vancomycin if possible 1

• Surgical intervention: Consider in patients with:

  • Perforation
  • Systemic inflammation unresponsive to antibiotics
  • Toxic megacolon
  • Severe ileus
  • Ideally before serum lactate exceeds 5.0 mmol/L 1, 4

Common Pitfalls to Avoid

• Don't rely solely on metronidazole for severe or recurrent cases 1, 6, 7
• Don't perform "test of cure" after treatment completion 1
• Don't delay treatment in severely ill patients while awaiting confirmatory testing 1
• Don't repeat testing within 7 days of a negative test (low yield) 1
• Don't use probiotics for prevention of CDI (not recommended by IDSA) 7

The treatment landscape for CDI has evolved significantly, with fidaxomicin and vancomycin now preferred over metronidazole for initial episodes, and FMT emerging as an effective option for multiple recurrences 6, 5, 7.