What is the second-line treatment for Clostridioides difficile (C. diff) infection after vancomycin (Vancomycin) failure?

Second-Line Treatment for C. difficile Infection After Vancomycin Failure

Fidaxomicin is the preferred second-line treatment for C. difficile infection after vancomycin failure, with a 10-day course at 200 mg twice daily being the recommended regimen. 1

Treatment Options for Recurrent C. difficile Infection

First Recurrence After Vancomycin

• Preferred treatment: Fidaxomicin 200 mg twice daily for 10 days 1

  • Alternative regimen: Fidaxomicin 200 mg twice daily for 5 days followed by once every other day for 20 days 1
  • Fidaxomicin is associated with a 63% reduction in risk of treatment failure compared to vancomycin in real-world settings 2
  • Recent studies show fidaxomicin significantly reduces CDI recurrence rates compared to vancomycin (HR 0.67,95% CI 0.50-0.90) 3

• Alternative: Vancomycin in a tapered and pulsed regimen 1

  • Example regimen: 125 mg 4 times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks 1
  • Note: Recent mouse model research suggests pulsed dosing may not effectively clear C. difficile colonization 4

Second or Subsequent Recurrences

1. Fidaxomicin 200 mg twice daily for 10 days 1

   • Alternative extended regimen: twice daily for 5 days followed by once every other day for 20 days 1

2. Vancomycin in a tapered and pulsed regimen 1

3. Vancomycin 125 mg 4 times daily for 10 days followed by rifaximin 400 mg 3 times daily for 20 days 1

4. Fecal microbiota transplantation (FMT) 1

   • Recommended after at least 2 recurrences (i.e., 3 CDI episodes) with appropriate antibiotic treatment 1
   • FMT is highly effective for patients with multiple CDI recurrences who have failed appropriate antibiotic treatments 1

Adjunctive Treatments

• Bezlotoxumab (10 mg/kg IV once during standard antibiotic therapy) 1
  • Human monoclonal antibody that reduces recurrent CDI by blocking C. difficile toxin B 1
  • Particularly beneficial for patients with:
    • CDI due to the 027 epidemic strain
    • Immunocompromised status
    • Severe CDI presentation 1
  • Caution: Use with care in patients with congestive heart failure 1

Important Considerations

• Avoid metronidazole for recurrent CDI 1

  • Lower sustained response rates compared to vancomycin 1
  • Risk of cumulative neurotoxicity with long-term use 1

• Antimicrobial resistance patterns

  • Resistance to vancomycin remains low (1.6%) 5
  • Fidaxomicin resistance is emerging but still relatively low (7.35%) 5

• Supportive care

  • Provide intravenous fluid resuscitation, electrolyte replacement, and albumin supplementation for patients with severe CDI 1
  • Consider discontinuing proton pump inhibitors if not essential 1

Emerging Treatments

• Ridinilazole and ibezapolstat show promising in vitro activity against C. difficile isolates and may become future treatment options 5

Monitoring

• For patients with severe disease, prolonged vancomycin exposure, or renal failure, consider monitoring vancomycin trough serum concentrations to rule out drug accumulation 1

Special Situations

• For fulminant CDI with ileus, consider adding intravenous metronidazole (500 mg every 8 hours) to oral or rectal vancomycin 1
• In patients not responding to standard therapy, intravenously administered tigecycline or passive immunotherapy with intravenous immunoglobulins may be considered 1