First-line Fecal Microbiota Transplantation Offers Resolution for Patients With Clostridiodes difficile, Study Says

A clinical trial found evidence supporting first-line fecal microbiota transplantation (early FMT), in addition to vancomycin, may be an effective treatment for early Clostridioides difficile infection. In fact, the study, conducted by the Aarhus University Hospital in Denmark between June 21, 2021 – April 1, 2022, was stopped early due to the superior results.

The primary outcome of this study found a 90% resolution of C difficile-associated diarrhea (CDAD) in patients that were given early FMT, with 85% of those patients having a negative Clostridioides difficile PCR test at week 8.

Secondary outcomes of the study were a 90% resolution of CDAD at week 1 for patients given early FMT, and that 78% of those patients had a negative C difficile PCR test at week 1.

For patients with recurrence of Clostridioides difficile as a result of treatment failure, rescue FMT was offered. Death and colectomy rates were recorded at week 8, as well as health-related quality of life.

This study is significant for being the first randomized, double-blind, placebo-controlled clinical trial for treating first or second Clostridioides  difficile infection by using FMT in addition to vancomycin. Clostridioides difficile infection is an antibiotic-associated health condition that has few treatment options.

The results of the study are extremely encouraging, says Simon Mark Dahl, MD, PhD student at the Department of Clinical Medicine and doctor at Aarhus University Hospital.

“Our new study shows that we can effectively cure the infection through the early use of fecal microbiota transplantation (FMT) after completing the standard treatment, to prevent relapses,” Dahl said in a statement.

The study initially screened 86 patients (aged 18 years or older) with first or second Clostridioides difficile infection, defined as 3 watery stools or more per day, and a positive Clostridioides difficile PCR test. Patients were recruited from referrals by regional physicians.

Criteria for exclusion included those who were pregnant or lactating, taking antibiotics other than vancomycin, allergic to vancomycin or had previous anaphylactic reactions to any food sources, taking any medication with a vancomycin interaction, or had continuous need for proton pump inhibitors, gastroparesis, and life-threatening fulfilment Clostridioides difficile infection.

Of those initial patients, 42 were enrolled in the study. Each patient was given 125 mg of oral vancomycin 4 times a day for a minimum of 10 days after diagnosis of Clostridioides difficile infection. Patients were then randomly assigned to either the encapsulated FMT (n = 21) group, or the encapsulated placebo (n = 21) group following standard treatment with vancomycin.

The FMT capsules were processed from 50 g of crude feces from five thoroughly screened and healthy blood donors. The crude stool was then homogenized in sterile saline and mixed with 85% glycerol that underwent centrifugation, yielding a median of 25 capsules. Each patient was then given FMT obtained from the same donor.

Clinical visits were scheduled at day 1, days 3-7, week 1, and 8 weeks after the second study treatment. For each visit, patients provided stool samples as well as venous blood samples.

As a result, 19 patients who received FMT completed their 8-week follow-up, while only 7 patients from the placebo group completed their 8-week follow up, due to recurrence of Clostridioides difficile infection.

A total of 204 adverse events were recorded during the follow-up. The most common adverse events were transient diarrhea (n = 23 in the transplantation group and n = 14 in the placebo group), abdominal pain (n = 14 in the transplantation group and n = 11 in the placebo group), and nausea (n = 12 in the transplantation group and n = 5 in the placebo group).

Three serious adverse events occurred during the 8-week follow-up that were possibly related to the study treatment.

Rescue FMT was performed in 2 patients in the transplantation group, and 13 patients in the placebo group who experienced recurrence. In addition, 2 of the 15 patients from the original placebo group died after receiving rescue FMT due to worsening pre-existing conditions. Another patient in the placebo group died before receiving rescue FMT.

Reference

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.