Microbial transfer from a healthy person’s stool is as effective at eliminating Clostridioides difficile infection (CDI) as antibiotic treatment, a phase III clinical trial has shown.
The research, in the Annals of Internal Medicine, showed a 5.4% numerical superiority with fecal microbiota transplantation (FMT) for adults with primary C. diff infection versus vancomycin, indicating its noninferiority to an antibiotic that is the standard of care.
The results suggest that FMT could be considered as a first-line treatment for primary CDI, representing a change to current practice and potentially avoiding the side effects of vancomycin treatment such as antibiotic-associated colitis.
“The results indicate that patients with primary C. difficile infections may be treated with fecal microbiota transplantation alone, and reserve antibiotics to patients with sustained symptoms after the fecal transplant,” researcher Frederik Juul, PhD, from Oslo University Hospital, told Inside Precision Medicine.
“This would reduce antibiotic use, which is a priority worldwide to reduce emerging antibiotic resistance.”
FMT is an established treatment for recurrent and refractory C. diff infection, but it is still somewhat controversial and is not widely available.
Guidelines released by the American Gastroenterological Association in 2024 endorse FMT for recurrent, refractory, or fulminant C. diff infection but state that the quality of evidence is low, citing bias, challenges with patient selection, lack of blinding, and lack of randomized, well-controlled, large studies.
To investigate further, Juul and co-workers conducted a randomized, open-label, noninferiority, multicenter trial at hospitals and primary care facilities in Norway. The study was designed as a noninferiority trial with a large margin of 25 percentage points, with the justification that a single FMT dose delivered by enema is a fast, minimally invasive procedure that limits the use of antibiotics that promote antimicrobial resistance.
The primary end point was clinical cure 14 days after the start of treatment with only the assigned treatment, consisting of a Bristol Stool Scale score less than four or less than three stools per day, and no recurrent CDI in the 60 days after the start of treatment.
The 104 participants were 18 years or older, had primary CDI, a positive stool test result for toxin-producing C. diff, and no diagnosis of CDI in the year prior to enrolling.
They were randomly assigned to receive either one enema using FMT from a national stool bank within 24 hours of randomization or standard-of-care treatment, consisting of 125 mg of oral vancomycin four times daily for 10 days.
The researchers report that 66.7% of patients in the FMT group and 61.2% of patients in the vancomycin group achieved the primary end point, thereby rejecting the hypothesis that response to FMT is 25 percentage points lower than response to vancomycin.
Adverse events did not significantly differ between the two groups, neither were there differences by sex, age or CDI severity.
In an editorial accompanying the study, Elizabeth Hohmann, MD, from Massachusetts General Hospital, commented: “The study emphasizes the importance of a healthy gut microbiome in preventing and treating this common nosocomial and community-acquired infection.
“It supports antibacterial stewardship in general and greater use of, access to, and insurance coverage for the FDA-approved stool-derived biologic products.”
She added that it highlighted the value of choosing the right patients for and timing of administration of gut microbial therapies is important.
“Selecting the right patients for and timing of administration of gut microbial therapies is important,” she maintained.
“We need a fast and inexpensive test for gut dysbiosis (perhaps based on a gut metabolomic readout) that could help direct us, independent of episode number.”
