CLINICAL QUESTION: Is fecal microbiota transplantation (FMT) safe and efficacious in the treatment of primary Clostridioides difficile infection (CDI)?
BACKGROUND: FMT is currently recommended for treatment of recurrent CDI, however, oral antibiotics, including vancomycin and fidaxomicin, remain the treatment of choice for primary CDI. Whether FMT may have a role in the treatment of primary CDI is unclear.
STUDY DESIGN: Open-label, phase 3, randomized, controlled trial
SETTING: Hospitals and primary care facilities in Norway
SYNOPSIS: A total of 100 adult participants with primary CDI and no previous CDI within one year were assigned to FMT versus vancomycin treatment arms. The primary endpoint was a composite of clinical cure (formed stools or less than three bowel movements daily) at 14 days and no disease recurrence within 60 days. The primary outcome was achieved in 66.7% of the FMT arm and 61.2% of the vancomycin arm. FMT versus vancomycin showed a difference in treatment response of 5.4% (95.2% confidence interval [CI], -13.5% to 24.4%) with a prespecified absolute noninferiority margin of 25%. The trial was stopped early due to meeting the prespecified noninferiority criterion for the primary endpoint in an interim analysis.
In the FMT arm 11 patients and in the vancomycin arm four patients received additional treatment for lack of clinical cure at day 14, or clinical deterioration. Secondary endpoint was clinical cure without recurrence, with or without additional treatment, and was achieved in 78.4% of the FMT arm and 61.2% of the vancomycin arm, with a difference in treatment response of 17.2% (92.5% CI, -0.7 to 35.1). There were no significant differences in the number of adverse events between treatment groups
BOTTOM LINE: FMT may have a role in the treatment of primary CDI, given a similar efficacy and safety profile as oral vancomycin, though availability and standardization of FMT processing and administration may remain a logistical barrier.
CITATION: Juul FE, et al. Fecal microbiota transplantation versus vancomycin for primary Clostridioides difficile infection: a randomized controlled trial. Ann Intern Med. 2025;178(7):940-947. doi: 10.7326/ANNALS-24-03285.
Ms. Hackett
Ms. Hackett is a physician assistant at the Nebraska Medical Center in Omaha, Neb.