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

Treatment Options for Clostridioides difficile Infection

Fidaxomicin 200 mg twice daily for 10 days is the preferred first-line treatment for non-severe initial C. difficile infection due to superior sustained clinical response rates and lower recurrence rates. 1

Treatment Algorithm Based on Disease Severity

Non-Severe Initial CDI

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

Severe CDI (hypotension, shock, ileus, or megacolon)

• Vancomycin 500 mg four times daily orally/via nasogastric tube 1
• Add rectal instillation of vancomycin if ileus is present 1
• Add intravenous metronidazole 500 mg every 8 hours 1

Recurrent CDI

• 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
• Second or subsequent recurrence: Consider fecal microbiota transplantation (FMT) after appropriate antibiotic treatments 1, 3
  • FMT shows 70-90% success rates in preventing further recurrences 1
  • Cochrane review demonstrates FMT likely leads to a large increase in resolution of recurrent CDI compared to alternative treatments (RR 1.92,95% CI 1.36 to 2.71) 3

Adjunctive Therapy

• Bezlotoxumab 10 mg/kg IV once during antibiotic administration may be considered, particularly for immunocompromised patients 1, 4
  • This monoclonal antibody targets C. difficile toxin B 5

Pediatric Dosing

For children aged 6 months and older 2:

• If able to swallow tablets and weighing ≥12.5 kg: 200 mg tablet twice daily for 10 days
• If unable to swallow tablets or <12.5 kg: Weight-based oral suspension dosing:
  • 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

Important Clinical Considerations

Monitoring Treatment Response

• Improvement expected within 2-3 days 1
• Reassess severity and consider alternative treatments if no improvement within 48-72 hours 1
• Monitor for peripheral neuropathy with prolonged metronidazole therapy 1
• Monitor renal function in patients over 65 years during and after vancomycin treatment 1

Risk Factors for Severe Disease

• Age >60 years
• Fever
• Hypoalbuminemia
• Peripheral leukocytosis
• ICU stay
• Abnormal abdominal CT findings 1

Infection Control Measures

• Strict hand hygiene with soap and water (not alcohol-based sanitizers) 1
• Contact precautions including isolation and personal protective equipment 1
• Thorough environmental cleaning 1
• Discontinue inciting antibiotic as soon as possible 1

Emerging Treatments

Recent developments in CDI treatment include:

• Defined microbiome biotherapeutics as safer alternatives to FMT 6
• Bacteriophages and their derivatives (endolysins and tailocins) 4
• Standardized defined microbial mixtures 4

Common Pitfalls to Avoid

1. Using metronidazole as first-line therapy: Current guidelines no longer recommend metronidazole as first-line treatment due to lower efficacy 1, 5
2. Failing to discontinue the inciting antibiotic: This is crucial to reduce recurrence risk 1
3. Inadequate monitoring: Patients should be reassessed within 48-72 hours to ensure treatment response 1
4. Overlooking infection control measures: Hand hygiene with soap and water is essential as alcohol-based sanitizers are ineffective against C. difficile spores 1
5. Delaying FMT consideration for multiple recurrences: FMT should be considered after two recurrences, as it significantly reduces further recurrence rates 1, 3