Fecal microbiota transplantation after vancomycin was superior to vancomycin alone at week 8 in patients with first or second Clostridioides difficile (C difficile) infection, according to study results published in The Lancet Gastroenterology & Hepatology.
The randomized, double-blind, placebo-controlled EarlyFMT trial was conducted at a tertiary gastroenterology referral center in Aarhus, Denmark, from June 21, 2021, to April 1, 2022. Eligible participants were aged at least 18 years with a first or second C difficile infection.
Patients were randomly assigned 1:1 to encapsulated fecal microbiota transplantation or encapsulated placebo after standard treatment with vancomycin. All participants received 125 mg oral vancomycin 4 times daily for a minimum of 10 days after a diagnosis of C difficile infection. Patients then received their allocated treatment twice after discontinuing vancomycin, with the first dose administered on day 1 and the second dose from days 3 to 7. The patients were followed up for 8 weeks after the final treatment or until C difficile recurrence.
The primary outcome was resolution of C difficile-associated diarrhea 8 weeks after the second study treatment, defined as a daily stool frequency of fewer than 3 for a minimum of 2 days regardless of C difficile fecal polymerase chain reaction (PCR) test result, or persistent diarrhea (≥3 watery stools daily) and a negative C difficile PCR test.
A total of 42 patients (women, 74%) were included in the study and assigned to the fecal microbiota transplantation group (n=21) or the placebo group (n=21). Their overall median age was 59 years (range, 25-89; IQR, 40-73), and the median treatment duration was 12 (IQR, 10-13) days. Of the cohort, 25 patients had a first C difficile infection, and 17 had a second C difficile infection.
The trial was stopped prematurely at the prespecified interim analysis due to a significantly lower rate of C difficile infection resolution in participants who received a placebo vs the fecal microbiota transplantation group.
At week 8, 19 (90%; 95% CI, 70-99) of 21 patients in the fecal microbiota transplantation group and 7 (33%; 95% CI, 15-57) of 21 patients in the placebo group (P =.00031) achieved resolution of C difficile-associated diarrhea. The absolute risk reduction for recurrence after fecal microbiota transplantation vs placebo was 57% (95% CI, 33-81).
In analysis involving stratification by C difficile episode, 13 (93%) of 14 patients with a first C difficile infection in the fecal microbiota transplantation group and 4 (36%) of 11 patients with first infection in the placebo group had resolution of C difficile-associated diarrhea at week 8. Of the participants who had a second C difficile infection, 6 (86%) of 7 patients in the fecal microbiota transplantation group and 3 (30%) of 10 in the placebo group had C difficile-associated diarrhea resolution at week 8.
During the follow-up, 204 adverse events were recorded, with at least 1 adverse event reported in 20 of 21 patients in the fecal microbiota transplantation group and in all 21 patients in the placebo group (P =1.00). The most frequently occurring adverse events were transient diarrhea (n=23 in the fecal microbiota transplantation group; n=14 in the placebo group), abdominal pain (n=14 in the fecal microbiota transplantation group; n=11 in the placebo group), and nausea (n=12 in the fecal microbiota transplantation group; n=5 in the placebo group).
A total of 3 serious adverse events occurred that were possibly related to study treatment — 1 in the fecal microbiota transplantation group and 2 in the placebo group.
Study limitations include the single-center design and regional uptake. In addition, the investigators assessed the additive effect of fecal microbiota transplantation after vancomycin, and, therefore, the findings should not be interpreted as evidence for fecal microbiota transplantation alone but for its use in combination with antibiotics.
“Our study corroborates the poor efficacy of the current standard of care antibiotics alone for the treatment of first or second infection with C difficile and proposes microbiota restoration with fecal microbiota transplantation as a necessary, effective first-line option,” the study authors wrote.
Baunwall SMD, Andreasen SE, Hansen MM, et al. Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. Published online September 21, 2022. doi:10.1016/S2468-1253(22)00276-X