Clostridioides difficile infection remains an urgent antibiotic-associated health threat, possessing only a few treatment options. Patients with multiple recurring episodes of C difficile may be treated with Microbiota restoration with faecal microbiota transplantation as an effective treatment option.

A recent study compared the efficacy and safety of faecal microbiota transplantation with placebo after vancomycin for first or second C difficile infection.

It included patients aged 18 years or older with first or second C difficile infection (defined as ≥3 watery stools [Bristol stool chart score 6-7] per day and a positive C difficile PCR test). The study randomized the Patients (1:1) to faecal microbiota transplantation or placebo administered on day one and between days 3 and 7 after receiving 125 mg oral vancomycin four times daily for ten days. It looked for the resolution of C difficile-associated diarrhea (CDAD) 8 weeks after treatment as the primary endpoint and followed up with patients for eight weeks or until recurrence. 

The study also planned to enroll 84 patients with a prespecified interim analysis after 42 patients. 

• The study consecutively screened 86 patients, randomly assigning 42 patients to faecal microbiota transplantation (n=21) or placebo (n=21).
• It stopped the trial after the interim analysis for ethical reasons because it identified a significantly lower resolution rate in the placebo group than in the faecal microbiota transplantation group.
• 90% of patients in the faecal microbiota transplantation group and 33% in the placebo group showed resolution of CDAD at week 8.
• It found 57% absolute risk reduction.
• Overall, 204 adverse events were described, with one or more occurring in most of the patients in the faecal microbiota transplantation group and in all patients in the placebo group.
• Diarrhea and abdominal pain were the most common adverse events.
• The study documented three serious adverse events possibly related to study treatment, but no deaths or colectomies during the 8-week follow-up.

This study describes that in patients with first or second C difficile infection, first-line faecal microbiota transplantation is highly effective and superior to the standard of care vancomycin alone in gaining sustained resolution from C difficile.

Baunwall SMD, Andreasen SE, Hansen MM, et al. Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomized, double-blind, placebo- controlled trial. Lancet Gastroenterol Hepatol. 2022 Sep 21; S2468-1253(22)00276-X. doi: 10.1016/S2468-1253(22)00276-X.