What is the recommended medication for Clostridioides difficile infection?

Recommended Medication for Clostridioides difficile Infection

For initial episodes of C. difficile infection (CDI), either oral vancomycin (125 mg four times daily) or fidaxomicin (200 mg twice daily) for 10 days is recommended over metronidazole as first-line therapy. 1

Treatment Algorithm Based on Disease Severity

Initial Episode Treatment

1. Non-severe CDI (WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL):

   • First choice: Oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 1
   • Alternative (if access to vancomycin/fidaxomicin is limited): Metronidazole 500 mg orally three times daily for 10 days 1
   • Caution: Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1

2. Severe CDI (WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL):

   • Oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days 1

3. Fulminant CDI (hypotension, shock, ileus, or megacolon):

   • Oral vancomycin 500 mg four times daily 1
   • If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1
   • Plus intravenous metronidazole 500 mg every 8 hours 1

Recurrent CDI Treatment

1. First Recurrence:

   • If metronidazole was used initially: Vancomycin 125 mg four times daily for 10 days 1
   • If standard vancomycin was used initially: Tapered and pulsed vancomycin regimen (e.g., 125 mg four times daily for 10-14 days, then twice daily for a week, once daily for a week, then every 2-3 days for 2-8 weeks) OR fidaxomicin 200 mg twice daily for 10 days 1, 2

2. Second or Subsequent Recurrence:

   • Vancomycin in a tapered and pulsed regimen 1
   • OR vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
   • OR fidaxomicin 200 mg twice daily for 10 days 1
   • OR fecal microbiota transplantation (after failing appropriate antibiotic treatments) 1, 3

Important Clinical Considerations

Evidence Quality and Treatment Selection

• The recommendation for vancomycin or fidaxomicin over metronidazole is based on high-quality evidence 1
• Fidaxomicin has shown lower recurrence rates compared to vancomycin (15.4% vs. 25.3%), particularly for non-NAP1 strains 4
• For first recurrences, fidaxomicin demonstrated a significantly lower second recurrence rate compared to vancomycin (19.7% vs. 35.5%) 2

Special Populations

• Pediatric patients (6 months to <18 years):
  • Non-severe CDI: Metronidazole or vancomycin 1
  • Severe/fulminant CDI: Vancomycin (with or without IV metronidazole) 1
  • Weight-based dosing: 10 mg/kg/dose of vancomycin four times daily (max 125 mg per dose for non-severe, 500 mg per dose for severe) 1

Common Pitfalls to Avoid

• Do not continue using the inciting antibiotic if possible, as this increases recurrence risk 1
• Do not use oral vancomycin or fidaxomicin for non-C. difficile infections as they have minimal systemic absorption 5, 6
• Do not use metronidazole for severe CDI or for multiple recurrences due to lower efficacy 1
• Do not use standard dose vancomycin for fulminant CDI; higher doses (500 mg QID) are recommended 1
• Do not overlook the possibility of vancomycin-induced nephrotoxicity, especially in patients >65 years 5

Adjunctive Measures

• Discontinue unnecessary proton pump inhibitors (PPIs) 1
• Implement antibiotic stewardship to minimize use of high-risk antibiotics (fluoroquinolones, clindamycin, cephalosporins) 1
• Consider empiric CDI therapy when substantial laboratory confirmation delay is expected 1

For patients with multiple recurrences who have failed appropriate antibiotic treatments, fecal microbiota transplantation has shown strong evidence of efficacy and should be considered 1.