What are the next steps for a patient with recurrent Clostridioides difficile (C. difficile) infection after treatment with vancomycin (Vancomycin) for 10 days and fidaxomicin (Fidaxomicin), with symptoms resolving for 2 weeks before returning?

Management of Recurrent C. difficile Infection After Failed Treatment with Vancomycin and Fidaxomicin

For a patient with recurrent C. difficile infection after failed treatment with vancomycin and fidaxomicin, fecal microbiota transplantation (FMT) is strongly recommended as the next step in management.

Assessment of Current Situation

The patient has experienced multiple treatment failures:

• Initial treatment with vancomycin for 10 days with incomplete response
• Subsequent treatment with fidaxomicin with temporary resolution (2 weeks) before recurrence

This pattern indicates:

• Multiple recurrent episodes of CDI (≥2 recurrences)
• Failure of both first-line (vancomycin) and second-line (fidaxomicin) therapies
• High risk for continued recurrence without more definitive intervention

Treatment Algorithm

1. Fecal Microbiota Transplantation (FMT)

FMT is strongly recommended as the next step based on:

• Strong recommendation with moderate quality evidence for FMT in patients with second and subsequent recurrences of CDI 1
• High clinical cure rates (70-92%) for recurrent CDI regardless of administration route 1
• Significantly higher clinical resolution compared to fidaxomicin (92% vs 42%, p=0.0002) in patients with recurrent CDI 1
• Demonstrated effectiveness in restoring intestinal microbiome diversity disrupted by repeated antibiotic courses 1

Administration options:

• Colonoscopic administration (highest success rates: 80-100%) 1
• Nasogastric/nasoduodenal route (success rates: 77-94%) 1
• Multiple FMT administrations may be required for optimal response (65% for one FMT, 80% for two, 90% for >2) 1

2. Alternative Approaches (If FMT is not available)

Extended/Tapered Vancomycin Regimen

• Vancomycin 125 mg four times daily for 10-14 days, followed by:
  • 125 mg twice daily for 7 days
  • 125 mg once daily for 7 days
  • 125 mg every 2-3 days for 2-8 weeks 2

Extended-Pulsed Fidaxomicin

• Consider extended-pulsed fidaxomicin regimen which has shown improved sustained response and lower recurrence rates (2% vs 17% with standard vancomycin) 1
• This regimen administers the same total dose as standard fidaxomicin but with extended dosing 1

Bezlotoxumab as Adjunctive Therapy

• Consider adding bezlotoxumab (monoclonal antibody against C. difficile toxin B) as adjunctive therapy with antibiotics 3
• Bezlotoxumab has demonstrated reduced CDI recurrence rates when used with standard of care antibiotics 3

Monitoring and Follow-up

• Daily assessment of bowel movements
• Monitor for resolution of symptoms (formed stools, reduced frequency)
• Electrolyte monitoring and correction as needed
• Fluid resuscitation if dehydration is present
• Renal function monitoring in patients over 65 years 2

Infection Control Measures

• Implement contact precautions
• Hand hygiene with soap and water (alcohol-based sanitizers are less effective against C. difficile spores)
• Environmental cleaning with hypochlorite agents or sporicidal products 2
• Discontinue any non-essential antibiotics that may have triggered CDI 2

Pitfalls and Caveats

1. Diagnostic challenges: Ensure that symptoms are truly due to recurrent CDI rather than post-infectious irritable bowel syndrome or other causes of diarrhea.

2. FMT considerations:

   • Donor screening is critical to prevent transmission of infectious agents
   • Reported infectious complications are rare but include potential transmission of norovirus 1
   • Physical complications related to administration procedure (upper GI bleeding with NG tube, colon perforation during colonoscopy) may occur at similar rates to these procedures performed for other indications 1

3. Treatment failures:

   • Multiple FMT administrations may be required for optimal response
   • Patients with hypervirulent strains (ribotypes 027,078, or 244) may have higher failure rates 1

4. Concomitant antibiotics:

   • Avoid unnecessary antibiotics during and after CDI treatment
   • If antibiotics are necessary for other infections, consider extending CDI treatment duration 4

The evidence strongly supports FMT as the most effective next step for this patient with multiple recurrences after standard therapies, with clinical cure rates significantly higher than continued antibiotic therapy alone 1.