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Disclosures:
Juul reports presenting for Tillotts Pharma. Please see the study for all other authors’ relevant financial disclosures.
Key takeaways:
- FMT appeared as effective as vancomycin in curing first-time C. difficile infection.
- Findings show FMT has potential as a safe, viable first-line treatment without antibiotic pretreatment.
Fecal microbiota transplantation was not inferior to vancomycin for the treatment of primary Clostridioides difficile infection, suggesting it could be a first-line option, according to research published in Annals of Internal Medicine.
“Our trial is the first large, phase 3 randomized trial in first-time, primary C. difficile infections comparing FMT to antibiotics, the recommended first-line treatment,” Frederik Emil Juul, MD, PhD, postdoctoral researcher at University of Oslo, told Healio. “We demonstrated that FMT is at least as effective as antibiotics in terms of treatment efficacy, and numerically, FMT actually seems to be better than antibiotics.”
Data were derived from Juul F, et al. Ann Intern Med. 2025;doi:10.7326/ANNALS-24-03285.
FMT has been established as a treatment option for recurrent C. difficile infection, whereas antibiotics such as vancomycin or fidaxomicin are recommended first-line treatment.
Prolonged antibiotic treatment is expensive, however, has adverse effects and contributes to antibiotic resistance, according to Juul and colleagues, who aimed to study FMT’s use as a primary treatment, as it addresses the cause of infection.
They conducted a multicenter, open-label, assessor-blinded, noninferiority trial of adults with primary C. difficile infection and no previous diagnosis of infection within the past 365 days.
The researchers randomly assigned patients to receive one FMT enema without antibiotic pretreatment (n = 51; median age, 70 years; 62.8% women) or 125 mg of oral vancomycin four times daily for 10 days (n = 49; median age, 71 years; 53.1% women).
Clinical cure, defined as fewer than three stools per day or firm stools for at least 48 hours at day 14, occurred in 70.6% of the FMT group and 77.6% of the vancomycin group at day 14.
The researchers defined noninferiority as a clinical cure rate with FMT more than 25 percentage points lower than with vancomycin.
Two-thirds (66.7%; 95% CI, 52.1%–79.2%) of the FMT group achieved the study’s primary endpoint of clinical cure without recurrence within 60 days compared with 61.2% (95% CI, 46.2%-74.8%) of the vancomycin group — a risk difference of 5.4 percentage points (P < .001 for non-inferiority).
Additional treatment was given to 11 patients in the FMT group and four in the vancomycin group, indicating 78.4% (95% CI, 64.7%-88.7%) of the FMT group and 61.2% (95% CI, 46.2%-74.8%) of the vancomycin group achieved the study’s secondary endpoint, defined as clinical cure at day 14, with or without additional treatment. The risk difference was 17.2 percentage points (P < .001 for non-inferiority).
Adverse events were comparable between the two groups and none were related to the treatment.
Seven patients died during the study period — two in the FMT group and five in the vancomycin group. One death in each group was due to recurrent C. difficile infection.
Frederik Emil Juul
“Based on the trial results, we conclude that FMT may have a role in primary C. difficile infections, not only after multiple recurrences,” Juul told Healio. “Our results show that antibiotic pretreatment may not be necessary to achieve clinical cure in primary C. difficile infections. With rigorous FMT donor screening and treatment preparation, FMT is safe and at least as effective as antibiotics.”
For more information:
Frederik Emil Juul, MD, PhD, can be reached at f.e.juul@medisin.uio.no.
