What treatment options are available for a patient with recurrent Clostridioides difficile (C. diff) symptoms after initial treatment with vancomycin and fidaxomicin (Dificid)?

Treatment for Recurrent C. difficile Infection After Vancomycin and Fidaxomicin

For patients with recurrent C. difficile infection after treatment with vancomycin and fidaxomicin, fecal microbiota transplantation (FMT) is the recommended treatment approach due to its high clinical cure rates of 70-90% in patients with multiple recurrences. 1

Treatment Algorithm for Recurrent CDI After Failed Standard Therapies

First-line approach:

• Fecal Microbiota Transplantation (FMT)
  • Indicated after failure of appropriate antibiotic treatments for at least two recurrences
  • Clinical cure rates between 70-90% 1
  • Should be considered as the primary intervention at this stage of recurrence

Alternative approaches (if FMT is not available):

1. Extended vancomycin taper and pulse regimen

   • Initial dose: 125 mg four times daily for 10-14 days
   • Then: 125 mg twice daily for 7 days
   • Then: 125 mg once daily for 7 days
   • Finally: 125 mg every 2-3 days for 2-8 weeks 1
   • Consider an even longer tapering schedule for multiple recurrences

2. Vancomycin followed by rifaximin

   • Vancomycin 125 mg four times daily for 10-14 days
   • Followed by rifaximin 400 mg three times daily for 20 days 1

3. Bezlotoxumab adjunctive therapy

   • Single infusion of bezlotoxumab administered during the course of standard of care antibiotics
   • Shown to reduce CDI recurrence rates (15.4% vs. 25.3% compared to placebo) 2
   • Can be administered during any standard of care antibiotic treatment

Important Clinical Considerations

Patient Assessment

• Evaluate for severity of recurrence:
  • Number of unformed bowel movements per day
  • WBC count
  • Signs of sepsis or organ dysfunction
• Monitor daily for:
  • Resolution of diarrhea
  • Electrolyte abnormalities
  • Fluid status

Contraindications and Precautions

• Discontinue any unnecessary antibiotics that may have triggered the CDI 1
• Avoid metronidazole for recurrent CDI due to:
  • Lower response rates
  • Risk of cumulative neurotoxicity with repeated courses 1

Prevention of Further Recurrence

• Implement contact precautions
• Proper hand hygiene with soap and water
• Environmental cleaning with hypochlorite or sporicidal products
• Antibiotic stewardship to minimize use of high-risk antibiotics 1

Evidence Analysis

The recommendation for FMT is supported by strong evidence showing 70-90% clinical cure rates in patients with multiple recurrences 1. This is particularly relevant for patients who have already failed both vancomycin and fidaxomicin, as standard antibiotic approaches have diminishing returns with each recurrence.

While fidaxomicin has been shown to have lower recurrence rates compared to vancomycin in initial episodes (16.1% vs 25.4%) 3, its efficacy is limited in patients who have already failed a course of fidaxomicin. The 2020 Taiwan guidelines note that in patients with recurrent CDI, fidaxomicin and vancomycin showed similar treatment failure rates in real-world settings 4.

Bezlotoxumab, a monoclonal antibody that binds to C. difficile toxin B, can be considered as an adjunctive therapy to reduce recurrence risk, with FDA data showing a recurrence rate of 15.4% versus 25.3% with placebo 2.

Surgical Considerations

For patients with severe complications such as toxic megacolon, colonic perforation, acute abdomen, or septic shock with organ failure, surgical intervention should be considered 1:

• Subtotal colectomy with preservation of the rectum (traditional approach)
• Diverting loop ileostomy with colonic lavage followed by antegrade vancomycin flushes (alternative approach)

By following this treatment algorithm, clinicians can effectively manage recurrent C. difficile infection in patients who have failed standard therapies with both vancomycin and fidaxomicin.