Can fecal microbiota therapy be used as a first-line treatment for C. difﬁcile?

Antibiotic-associated colitis due to Clostridioides difﬁcile infection (CDI) is an important health problem. Currently recommended therapy for primary infection is antibiotic treatment with vancomycin or ﬁdaxomicin. However, 10%-to-20% of patients experience one or more symptom recurrences after initial successful antibiotic therapy. As a result, repeated and prolonged antibiotic regimens have often been necessary. Antibiotic therapy is expensive, causes considerable adverse effects and patient burden, and promotes antibiotic resistance (e.g., vancomycin-resistant Enterococcus). Therefore, it is desirable to reduce antibiotic use in CDI.1In March 2025, Health Canada approved the first fecal microbiota therapy—Rebyota (fecal microbiota, live 1×108 to 5×1010 colony forming units/mL, 150 mL rectal suspension; Ferring). It is indicated for the prevention of recurrence of Clostridioides difficile infection (CDI) in adults following antibiotic treatment for recurrent CDI. It is not indicated for initial CDI treatment.2 Although fecal microbiota therapy is recommended (and approved in Canada) for prevention of recurrent CDI, its role in the treatment of primary CDI is unclear. To investigate this issue, researchers in Oslo, Norway studied the efﬁcacy and safety of fecal microbiota therapy in primary CDI.1The randomized, open-label, noninferiority, multicentre trial was conducted in hospitals and primary care facilities in Norway. The study group included adults with CDI (C. difﬁcile toxin in stool and ≥ 3 loose stools daily) and no previous CDI within 365 days before enrollment.1Patients were randomly assigned in a 1:1 ratio to receive either fecal microbiota therapy (one enema administered rectally within 24 hours of randomization, without any antibiotic pretreatment), or standard-of-care treatment with oral vancomycin (125 mg capsules orally four times daily for 10 days). The fecal microbiota therapy used in the trial was delivered by the Norwegian stool donor bank.1The primary end point was clinical cure (ﬁrm stools or < 3 bowel movements daily) at day 14 and no disease recurrence within 60 days with the assigned treatment alone. Key secondary end points were clinical cure at day 14 with or without additional treatment (metronidazole, vancomycin, ﬁdaxomicin or fecal microbiota therapy) and no recurrent CDI within 60 days, and adverse events.1Results showed the following:100 patients received fecal microbiota therapy or vancomycin and were eligible for analysis.Clinical cure and no disease recurrence within 60 days without additional treatment was seen in 34 of 51 patients (66.7%) with fecal microbiota therapy versus 30 of 49 (61.2%) with vancomycin (difference, 5.4 percentage points [95.2% CI, -13.5 to 24.4 percentage points]; p < 0.001 for noninferiority vs vancomycin).11 patients in the fecal microbiota therapy group and four in the vancomycin group received additional C. difﬁcile treatment, predominantly oral vancomycin (10 [91%] in the fecal microbiota therapy group and 3 [75%] in the vancomycin group).Clinical cure at day 14 and no recurrence with or without additional treatment was observed in 40 of 51 patients (78.4%) with fecal microbiota therapy and 30 of 49 (61.2%) with vancomycin (difference, 17.2 percentage points [95.2% CI, -0.7 to 35.1 percentage points]).No signiﬁcant differences were seen between the two groups in the number of adverse events or serious adverse events.1 The authors conclude that based on the results of this study, fecal microbiota therapy may be considered as ﬁrst-line therapy in primary CDI. It has the potential to change the current practice of using antibiotic therapy as the ﬁrst-line treatment for primary CDI. The authors contend that antibiotics could be reserved for patients who are not cured with fecal microbiota therapy or for those who develop recurrence after fecal microbiota therapy. Additional doses of fecal microbiota therapy could also be considered, as this has been shown to increase the treatment success rate in recurrent CDI. The authors advocate for giving all patients with primary CDI and their caregivers the chance to consider fecal microbiota therapy.1References:Juul FE, Bretthauer M, Johnsen PH, et al. Fecal microbiota transplantation versus vancomycin for primary Clostridioides difﬁcile infection. A randomized controlled trial. Ann Intern Med 2025; published online June 17, 2025. (accessed June 26, 2025). Ferring Inc. Rebyota (fecal microbiota, live rectal suspension) product monograph. North York, ON; March 5, 2025. (accessed June 26, 2025).

Can fecal microbiota therapy be used as a first-line treatment for C. difﬁcile?

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