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

Treatment Approach for Recurrent Clostridioides difficile Infection

For recurrent C. difficile infection, a tapered and pulsed vancomycin regimen, fidaxomicin, or fecal microbiota transplantation should be used based on the number of recurrences, with FMT being the most effective option for multiple recurrences. 1

First Recurrence Treatment

For patients experiencing their first recurrence of CDI, treatment options include:

1. If metronidazole was used for initial episode:

   • Vancomycin 125 mg four times daily orally for 10 days 1

2. If standard vancomycin was used for initial episode:

   • Vancomycin in a tapered and pulsed regimen:
     • 125 mg four times daily for 10-14 days
     • 125 mg twice daily for 7 days
     • 125 mg once daily for 7 days
     • 125 mg every 2-3 days for 2-8 weeks 1

   OR

   • Fidaxomicin 200 mg twice daily orally for 10 days 1

Fidaxomicin has demonstrated lower recurrence rates (19.7%) compared to standard vancomycin (35.5%) in patients with first recurrence (p=0.045) 2, making it a valuable option especially for patients at high risk for subsequent recurrences.

Second or Subsequent Recurrences

For patients with two or more recurrences, treatment options include:

1. Vancomycin tapered and pulsed regimen (as described above) 1

2. Vancomycin followed by rifaximin:

   • Vancomycin 125 mg four times daily for 10 days, then
   • Rifaximin 400 mg three times daily for 20 days 1

3. Fidaxomicin 200 mg twice daily for 10 days 1

4. Fecal microbiota transplantation (FMT):

   • Strongly recommended after failure of appropriate antibiotic treatments for multiple recurrences 1
   • Success rates range from 70-92% regardless of administration route 1
   • Multiple FMT administrations increase success rates (65% for one FMT, 80% for two, and 90% for more than two) 1

Adjunctive Therapy for High-Risk Patients

For patients at high risk of recurrence (age ≥65, immunocompromised, severe CDI at presentation, or prior CDI episodes):

• Bezlotoxumab (monoclonal antibody against C. difficile toxin B):
  • Single intravenous infusion given concurrently with antibiotic treatment
  • Reduces recurrence rates in high-risk patients 3
  • Should be used in conjunction with standard antibiotic therapy, not as monotherapy 3

Treatment Algorithm Based on Recurrence Number

1. First Recurrence:

   • If initial treatment was metronidazole: Vancomycin 125 mg four times daily for 10 days
   • If initial treatment was vancomycin: Fidaxomicin 200 mg twice daily for 10 days OR vancomycin tapered/pulsed regimen

2. Second Recurrence:

   • Vancomycin tapered and pulsed regimen
   • Fidaxomicin 200 mg twice daily for 10 days
   • Vancomycin followed by rifaximin

3. Third or More Recurrences:

   • Fecal microbiota transplantation
   • Consider bezlotoxumab as adjunctive therapy with antibiotics

Important Clinical Considerations

• Metronidazole is not recommended for recurrent CDI due to lower response rates and potential neurotoxicity with prolonged use 1

• Extended duration vancomycin regimens (taper and pulse) have shown superior outcomes (58-100% success) compared to pulse-only regimens (26-81%) 4

• Risk factors for recurrence that should guide treatment decisions:

  • Advanced age (≥65 years)
  • Continued use of antibiotics during or after CDI treatment
  • Immunocompromised state
  • Severe CDI at presentation
  • Prior CDI episodes within 6 months
  • Hypervirulent strains (ribotype 027) 1, 3

• Treatment failure signs requiring escalation of therapy:

  • Persistent diarrhea beyond 5-7 days of appropriate therapy
  • Worsening clinical status despite treatment
  • Development of severe complications (toxic megacolon, ileus)

By following this evidence-based approach to recurrent CDI, clinicians can optimize treatment outcomes and reduce the risk of further recurrences, ultimately improving patient morbidity and mortality.