What is the role of fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile (C. diff) infections?

Fecal Microbiota Transplantation for Recurrent C. difficile Infection

Fecal microbiota transplantation (FMT) should be offered to patients with recurrent Clostridioides difficile infection (CDI) who have had at least two recurrences, or those who have had one recurrence with risk factors for further episodes. 1

Indications for FMT in CDI

Recommended Uses:

1. Recurrent CDI

   • Defined as at least two recurrences (three total episodes)
   • Or one recurrence with risk factors for further episodes including:
     • Severe or severe-complicated CDI
     • Advanced age (>65 years)
     • Immunocompromised status (with caution)
     • Ongoing antibiotic use for other indications

2. Refractory CDI

   • Cases not responding to appropriate antibiotic therapy 1

3. After Initial FMT Failure

   • FMT should be repeated if the first attempt fails 1

4. Severe or Fulminant CDI

   • As adjuvant treatment in hospitalized patients not responding to standard antibiotics 1

Not Recommended:

• Initial therapy for CDI - Standard antibiotics remain first-line treatment 1
• Severely immunocompromised patients - FMT should be avoided 1
• Non-CDI indications - Not recommended for IBD or IBS outside clinical trials 1

Patient Selection and Considerations

Pre-FMT Assessment:

• Confirm diagnosis with appropriate testing (nucleic acid amplification or glutamate dehydrogenase in combination with toxin testing)
• Complete standard antibiotic course for CDI before FMT
• Assess immunocompromised status:
  • Mild/moderate immunosuppression: FMT may be offered with caution
  • Severe immunosuppression: FMT is not recommended 1

Special Populations:

• Inflammatory Bowel Disease: FMT can be offered but patients should be counseled about risk of IBD flare 1
• Immunocompromised patients: Use with caution; screen donors for EBV and CMV if recipient is at risk 1
• Other comorbidities: FMT can be considered regardless of other comorbidities 1

Administration and Follow-up

Administration Routes:

• Lower GI delivery (colonoscopy)
• Upper GI delivery (nasogastric/nasoduodenal tube)
• Both routes appear effective, though colonoscopic delivery may have slightly higher cure rates

Post-FMT Management:

1. Follow endoscopy unit protocol for immediate post-procedure care
2. Patients may have enteral tubes removed and oral water given from 30 minutes post-administration
3. Follow-up for at least 8 weeks to establish efficacy and monitor for adverse events 1

Adverse Events:

• Common short-term effects: self-limiting GI symptoms (bloating, cramps, diarrhea)
• Serious adverse events are rare but include:
  • Potential infection transmission
  • Procedure-related complications
  • IBD flares in susceptible patients 1

Efficacy and Outcomes

FMT has demonstrated high efficacy for recurrent CDI:

• Cure rates of approximately 80-90% after a single FMT
• Efficacy increases to >90% with repeat FMT if needed
• Significantly reduces mortality and morbidity compared to antibiotic therapy alone 1

Donor Selection

• Unrelated donors from centralized stool banks are preferred when available
• Donors should be screened for:
  • Infectious diseases
  • Gastrointestinal disorders
  • Metabolic conditions
  • Recent antibiotic use
  • EBV and CMV status for immunocompromised recipients 1

Common Pitfalls to Avoid

1. Using FMT as first-line therapy - Standard antibiotics remain first-line
2. Inadequate follow-up - Monitor for at least 8 weeks post-FMT
3. Routine C. difficile testing after FMT - Only test if symptoms recur
4. Overlooking donor screening - Thorough donor screening is essential
5. Using FMT in severely immunocompromised patients - Higher risk of adverse events

Emerging Developments

FDA-approved microbiota-based therapies are now available as alternatives to conventional FMT:

• Fecal microbiota live-jslm
• Fecal microbiota spores live-brpk

These standardized preparations may offer advantages in terms of consistency and safety compared to conventional FMT 1.

FMT represents a significant advancement in treating recurrent CDI by restoring gut microbiota diversity and function, providing an effective option for patients who have failed standard antibiotic therapy.