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

Treatment for Clostridioides difficile Infection

For C. diff infection, oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) are the first-line treatments, with treatment selection based on disease severity and recurrence status. 1

Disease Classification and Treatment Algorithm

Non-severe C. diff Infection

• Defined as: Leukocyte count ≤15,000 cells/mL and serum creatinine <1.5 mg/dL 1
• First-line treatment:
  • Oral vancomycin 125 mg four times daily for 10 days OR
  • Oral fidaxomicin 200 mg twice daily for 10 days 1, 2
  • Note: Metronidazole is no longer recommended as first-line therapy for adults 3

Severe C. diff Infection

• Defined as: Leukocyte count >15,000 cells/mL or serum creatinine ≥1.5 mg/dL 1
• Treatment:
  • Oral vancomycin 125 mg four times daily for 10 days (higher doses may be considered) 1
  • Fidaxomicin 200 mg twice daily for 10 days is an alternative 1, 2

Fulminant/Complicated C. diff Infection

• Characterized by: Hypotension, shock, ileus, or megacolon
• Treatment:
  • Oral vancomycin 500 mg four times daily PLUS
  • Intravenous metronidazole 500 mg every 8 hours
  • Add rectal vancomycin if ileus is present 1

Management of Recurrent C. diff Infection

First Recurrence

• If metronidazole was used initially:
  • Switch to standard course of oral vancomycin 1
• If vancomycin was used initially:
  • Consider prolonged and pulsed regimen of vancomycin OR
  • Switch to fidaxomicin 200 mg twice daily for 10 days 1

Multiple Recurrences

• Options include:
  • Vancomycin taper and pulse regimen
  • Fidaxomicin extended regimen
  • Fecal microbiota transplantation (FMT) for patients with multiple recurrences who have received appropriate antibiotic therapy for at least three episodes 1, 3
  • Consider bezlotoxumab as adjunctive therapy, particularly in immunocompromised patients 1, 4

Important Clinical Considerations

Diagnostic Approach

• Test patients with ≥3 unformed stools in 24 hours without laxative use 3
• Recommended testing: Two-step protocol using nucleic acid amplification tests (NAATs) or glutamate dehydrogenase (GDH) assay as initial screen, followed by toxin A/B detection for positive screens 1

Antibiotic Stewardship

• Discontinue the inciting antibiotic as soon as possible 1
• Discontinue unnecessary proton pump inhibitors (PPIs) to reduce risk of recurrence 1, 4

Infection Control Measures

• Implement isolation until 48 hours after diarrhea resolution 1
• During outbreaks, hand hygiene with soap and water is superior to alcohol-based products 3

Special Populations

• Pediatric patients: Fidaxomicin is FDA-approved for patients aged 6 months and older 2
• Elderly patients: Monitor renal function during and after treatment 1
• Immunocompromised patients: Consider adjunctive bezlotoxumab to prevent recurrence 1

Treatment Pitfalls to Avoid

• Relying on metronidazole as first-line therapy, which is now considered inferior to vancomycin and fidaxomicin 3, 5
• Failing to discontinue the inciting antibiotic, which increases risk of treatment failure and recurrence 1
• Not adjusting therapy based on disease severity or recurrence status 1
• Using probiotics for prevention of C. diff infection, which is not recommended by IDSA 3
• Inadequate diagnostic testing (single-step testing may lead to under- or misdiagnosis) 6

The treatment landscape for C. diff infection has evolved significantly, with vancomycin and fidaxomicin replacing metronidazole as preferred agents due to higher cure rates and lower recurrence rates 6, 4. For patients with multiple recurrences, FMT has emerged as an effective option with high cure rates 5, 4.