Fecal Microbiota Suspension Considered Safe for Recurrent C. Difficile Infection


Fecal microbiota transplantation is a process that restores bacterial diversity in the gut microbiome after standard-of-care antimicrobial therapy.

Live-jslm (Rebyota; Ferring Pharmaceuticals, Inc) is a safe treatment for adults with recurrent Clostridioides difficile (C.diff) infection (rCDI), according to a study published in Therapeutic Advancements in Gastroenterology.

Image credit: Yurii Kibalnik - stock.adobe.com

Image credit: Yurii Kibalnik - stock.adobe.com

This fecal microbiota suspension is the first FDA-approved, single-dose, microbiota-based live biotherapeutic that prevents rCDI in adult patients who were already treated with an antibiotic. Fecal microbiota transplantation (FMT) is a process that restores bacterial diversity in the gut microbiome after standard-of-care antimicrobial therapy.

“FMT is generally considered safe in the short term when rigorous donor screening procedures are employed,” the study authors wrote in the article. “However, data and long-term follow-up from prospective, placebo-controlled trials of FMT are limited.”

Investigators performed an integrated analysis of 5 prospective clinical trials (4 completed, 1 ongoing) to a safety database that informs about the safety and tolerability of fecal microbiota RBL for rCDI. It is the largest safety evaluation of any microbiota-based live biotherapeutic product.

In the study, investigators evaluated treatment-emergent adverse events (TEAEs) at 6 months after treatment, and 1 study evaluated outcomes at 2 years. The most common TEAEs associated with RBL were mild to moderate diarrhea, abdominal pain, and nausea soon after FMT. Most can be attributed to treatment failure, recurrence, or another preexisting condition, and most were resolved within days.

CDI is the primary cause of infectious diarrhea in hospitalized patients. A healthy human colon contains diverse bacteria that work together to promote overall health and fight pathogens, but patients with CDI experience gut dysbiosis. This allows C.diff spores to germinate and cause diarrheal disease (CDI), “a serious illness that can lead to complications…the risks of which increase with each subsequent CDI recurrence,” the study authors wrote in the paper.

In a separate analysis, this subsequent risk was worse for patients aged 65 years and older. Older adults who had 3 episodes of rCDI had an increased risk of death by 39%. Fortunately, the rate of all-cause death, measured at follow-up, was very small with RBL treatment.

The entire analysis included 5 trials—PUNCH CD, PUNCH CD2, and PUNCH Open-Label were phase 2 trials whereas PUNCH CD3 and PUNCH CD3-OLS were phase 3 trials—with more than 1000 participants, aged 18 years and older, who were previously treated with standard-of-care antibiotic therapy for rCDI. Patients received 1 or 2 doses of Rebyota or placebo rectally. At 8 weeks, patients from either cohort who had recurrence could join an open-label Rebyota trial.

Rebyota is a 150-mL microbiota suspension developed from human fecal matter that was donated from qualified donors, screened and tested for pathogens according to FDA recommendations, and combined in a pre-defined ratio in a solution of polyethylene glycol (PEG) 3350 and saline. The suspension contains 1 × 108 and 5 × 1010 colony forming units (CFU) per mL of fecal microbes.

There were no infections derived from donors, but human fecal matter may contain infectious agents, which always poses a risk. It is important to update standard screening and testing as it relates to FDA requirements.

“[Rebyota] was optimized for patient safety through rigorous donor screening, standardized manufacturing protocols, and a noninvasive delivery mechanism,” the study authors wrote. “The integrated data from 5 prospective clinical trials provide further evidence [Rebyota] is a safe and well-tolerated treatment for patients with rCDI.”


Lee C, Louie T, Dubberke E, et al. Safety of fecal microbiota, live-jslm (REBYOTA™) in individuals with recurrent Clostridioides difficile infection: data from five prospective clinical trials. Therap Advs in Gastro. 2023;16. doi.org/10.1177/17562848231174277

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