When would you use Rebyota (Fecal Microbiota Transplantation) for an adult patient with recurrent Clostridioides (C. difficile) infection?

When to Use Rebyota for Recurrent C. difficile Infection

Use Rebyota in adults 18 years and older for prevention of recurrent Clostridioides difficile infection after completing standard antibiotic therapy, specifically after at least the second recurrence (third total episode) or in select high-risk patients after earlier recurrences. 1

Primary Indication

Rebyota (fecal microbiota, live-jslm) is FDA-approved specifically for prevention of recurrent CDI, not for acute treatment of active infection. 1 The American Gastroenterological Association recommends fecal microbiota-based therapies upon completion of standard antibiotic treatment for recurrent CDI in immunocompetent adults. 2

Timing of Administration

When to Consider Rebyota:

• After the second recurrence (third total CDI episode) is the standard threshold 2, 3
• After the first recurrence in select high-risk patients, including those who: 2, 3
  • Recovered from severe or fulminant CDI
  • Have particularly treatment-refractory CDI
  • Have significant comorbidities that would make another recurrence especially morbid

Administration Window:

• Give Rebyota 24-72 hours after completing standard antibiotic therapy for CDI 1
• Ensure CDI symptoms are controlled before administration 1
• Do not use during active CDI infection 1

Patient Selection Criteria

Appropriate Candidates:

• Immunocompetent adults with documented recurrent CDI 2
• Mildly or moderately immunocompromised adults (though conventional FMT is preferred over FDA-approved products like Rebyota in this population, as there is insufficient evidence for Rebyota specifically) 2
• Patients with inflammatory bowel disease can receive Rebyota, with safety and efficacy demonstrated in this population 4

Contraindications and Cautions:

• Do NOT use in severely immunocompromised patients, including those with: 2

  • Active cytotoxic therapy for solid tumors or hematologic malignancies
  • Recent chimeric antigen receptor T-cell therapy or hematopoietic cell transplant (when neutropenic)
  • Any neutropenia
  • Severe primary immunodeficiency
  • Advanced or untreated HIV (CD4 <200/mm³)

• Do NOT use in patients with severe allergic reactions (anaphylaxis) to product components 1

• Exercise caution in patients requiring frequent or long-term antibiotics, as ongoing antibiotic use may diminish Rebyota's efficacy 2, 3

• Be aware of potential food allergens in the product, as it is manufactured from human fecal matter 1

Diagnostic Confirmation Required

Before considering Rebyota, confirm recurrent CDI with: 2

• Clinically significant diarrhea (≥3 unformed stools in 24 hours)
• Positive testing using nucleic acid amplification test (NAAT) or glutamate dehydrogenase plus toxin enzyme immunoassay
• Improvement with C. difficile-directed antibiotics
• Recurrence within 8 weeks of completing prior CDI antibiotic treatment

Important pitfall: Rule out alternative diagnoses if symptoms are atypical (e.g., diarrhea alternating with constipation) or if there's no response to vancomycin or fidaxomicin. 2

Administration Details

• Route: Single 150 mL dose administered rectally via enema 1
• Alternative route: Can be administered via colonoscopy to the right colon 5
• Patient positioning: Keep patient in left-side or knee-chest position for up to 15 minutes after administration 1

Expected Outcomes

• Treatment success at 8 weeks: 73.8-78.9% 4, 6
• Sustained clinical response at 6 months: 91.0-92.7% in those who achieved initial treatment success 6, 5
• Most common adverse reactions (≥3%): abdominal pain (8.9%), diarrhea (7.2%), abdominal distention (3.9%), flatulence (3.3%), nausea (3.3%) 1

Alternative Considerations

If Rebyota is declined or unavailable, reasonable alternatives include: 7, 3

• Vancomycin tapered-pulsed regimen
• Tapered-pulsed fidaxomicin
• Bezlotoxumab 10 mg/kg IV once during antibiotic administration
• Other FDA-approved fecal microbiota products (e.g., Vowst/fecal microbiota spores live-brpk)

Critical Safety Requirement

Appropriate medical treatment must be immediately available for potential acute anaphylactic reactions following Rebyota administration. 1