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

Treatment of Clostridioides difficile Infection

Fidaxomicin 200 mg twice daily for 10 days is the preferred first-line treatment for Clostridioides difficile infection in adults, with vancomycin 125 mg four times daily for 10 days as an acceptable alternative. 1

Initial Treatment Based on Disease Severity

Non-severe CDI

• Adults:

  • First-line: Fidaxomicin 200 mg PO twice daily for 10 days 1, 2
  • Alternative: Vancomycin 125 mg PO four times daily for 10 days 3, 4

• Children:

  • First-line: Metronidazole 7.5 mg/kg/dose PO three or four times daily for 10 days (maximum 500 mg per dose) 3
  • Alternative: Vancomycin 10 mg/kg/dose PO four times daily for 10 days (maximum 125 mg per dose) 3

Severe CDI

• Adults:

  • Vancomycin 125 mg PO four times daily for 10 days 3, 1
  • Fidaxomicin 200 mg PO twice daily for 10 days 1, 2

• Children:

  • Vancomycin 10 mg/kg/dose PO four times daily for 10 days (maximum 500 mg per dose) 3

Fulminant CDI

• Adults and Children:
  • Vancomycin 500 mg PO/NG four times daily PLUS
  • Metronidazole 500 mg IV three times daily 3, 1
  • Consider adding intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours if ileus is present 1

Management of Recurrent CDI

First Recurrence

• Adults:

  • Fidaxomicin 200 mg PO twice daily for 10 days 3, 1
  • Alternative: Vancomycin in a tapered and pulsed regimen 3

• Children:

  • Metronidazole 7.5 mg/kg/dose PO three or four times daily for 10 days (if first episode was treated with metronidazole) 3
  • Vancomycin 10 mg/kg/dose PO four times daily for 10 days (if first episode was treated with vancomycin) 3

Second or Subsequent Recurrence

• Adults and Children:
  • Vancomycin in a tapered and pulsed regimen 3, 1
  • Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 3
  • Fecal microbiota transplantation (FMT) for multiple recurrences that have failed appropriate antibiotic treatments 3, 1
  • Consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) as adjunctive therapy in patients with high risk of recurrence 1, 5

Important Considerations

Antibiotic Stewardship

• Discontinue the inciting antibiotic as soon as possible 3, 6
• Avoid unnecessary antibiotics, particularly fluoroquinolones, clindamycin, and cephalosporins 3, 5

Monitoring

• Monitor for symptom resolution 1
• In patients >65 years, monitor renal function during and after treatment with vancomycin due to risk of nephrotoxicity 4
• For patients on warfarin, monitor INR every 2-3 days during antibiotic treatment 1

Emerging Therapies

• Bezlotoxumab (10 mg/kg IV once during antibiotic treatment) for patients at high risk for recurrence 1, 7
• Live biotherapeutic products are being developed as alternatives to FMT 7, 6

Surgical Management

• Consider surgical intervention for:
  • Colonic perforation
  • Systemic inflammation not responding to antibiotic therapy
  • Toxic megacolon or severe ileus
  • Serum lactate >5.0 mmol/L 1

The treatment approach for C. difficile has evolved significantly in recent years, with fidaxomicin now preferred over metronidazole for initial episodes due to better clinical outcomes and lower recurrence rates. Vancomycin remains an effective alternative, especially when fidaxomicin is unavailable or cost-prohibitive. For recurrent cases, tapered vancomycin regimens, combination therapy with rifaximin, or FMT have shown promising results. Early recognition and appropriate treatment based on disease severity are crucial for optimal outcomes.