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

Treatment of Clostridioides difficile Infection

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 recommended first-line treatments, with fidaxomicin preferred for non-severe initial CDI. 1

Treatment Algorithm Based on Disease Severity

Initial Episode

1. Non-severe CDI:

   • First-line: Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
   • Alternative: Vancomycin 125 mg orally four times daily for 10 days 1
   • Limited option: Metronidazole 500 mg orally three times daily for 10 days (only for patients ≤65 years when other options unavailable) 1

2. Severe CDI (characterized by hypotension, shock, ileus, or megacolon):

   • Vancomycin 500 mg orally four times daily 1
   • Add intravenous metronidazole 500 mg every 8 hours if complications present 1
   • If ileus present, add rectal instillation of vancomycin 500 mg in 100 mL normal saline every 4-12 hours 1

Recurrent CDI

1. First recurrence:

   • Fidaxomicin 200 mg twice daily for 10 days OR
   • Fidaxomicin 200 mg twice daily for 5 days followed by once every other day for 20 days 1

2. Second or subsequent recurrence:

   • Consider fecal microbiota transplantation (FMT) after appropriate antibiotic treatment for at least 2 recurrences (70-90% success rate) 1, 3
   • Bezlotoxumab 10 mg/kg IV once during antibiotic administration may be considered as adjunctive therapy, particularly for immunocompromised patients 1

Pediatric Dosing

For children 6 months and older 2:

• Weight-based dosing for fidaxomicin oral suspension:
  • 4 kg to <7 kg: 80 mg (2 mL) twice daily
  • 7 kg to <9 kg: 120 mg (3 mL) twice daily
  • 9 kg to <12.5 kg: 160 mg (4 mL) twice daily
  • ≥12.5 kg: 200 mg (5 mL) twice daily
• Children ≥12.5 kg who can swallow tablets: one 200 mg tablet twice daily
• Alternative: Metronidazole 7.5 mg/kg/dose (maximum 500 mg) three or four times daily for 10 days 1

Infection Control Measures

• Hand hygiene: Use soap and water rather than alcohol-based sanitizers 1
• Contact precautions: Isolation and personal protective equipment 1
• Environmental cleaning: Thorough disinfection of patient environment 1
• Antibiotic stewardship: Discontinue the inciting antibiotic as soon as possible 1

Monitoring and Follow-up

• Expect clinical improvement within 2-3 days of starting treatment 1
• If no improvement within 48-72 hours, reassess severity and consider alternative treatment 1
• Monitor for peripheral neuropathy in patients on metronidazole 1
• Monitor renal function in patients >65 years receiving vancomycin 1

Important Clinical Considerations

• Fidaxomicin has lower recurrence rates compared to vancomycin and should be considered as preferred first-line therapy for non-severe initial CDI 1, 4
• Metronidazole is no longer recommended as first-line therapy for adults 4
• Risk factors for severe disease include age >60 years, fever, hypoalbuminemia, peripheral leukocytosis, ICU stay, and abnormal abdominal CT findings 1
• FMT should be strongly considered for multiple recurrences, especially in elderly patients who may not tolerate surgical interventions 3
• Bezlotoxumab can be considered for patients at high risk for recurrence 1

Common Pitfalls to Avoid

• Diagnostic delay: Test for C. difficile in patients with ≥3 unformed stools in 24 hours without laxative use 4
• Inappropriate continuation of inciting antibiotics: Discontinue the causative antibiotic as soon as possible 1
• Inadequate infection control: Failure to implement proper hand hygiene and contact precautions can lead to spread 1
• Overuse of metronidazole: No longer first-line therapy due to lower cure rates 4
• Delayed recognition of severe disease: Monitor for signs of severe infection requiring more aggressive treatment 1
• Failure to consider FMT for recurrent cases: FMT has high success rates (70-90%) for preventing further recurrences 1, 3