Preventing Recurrent C difficile in Real-World Clinical Practice

Fecal microbiota, live-jslm (Rebyota, RBL) has been FDA-approved for over 3 years now. RBL is indicated for the prevention of recurrent Clostridioides difficile infection (rCDI) in adults following antibiotic treatment.

As such, data around real-world clinical practice with the therapeutic for C difficile is being collected and analyzed. For example, the RebyOtA Prospective Registry (ROAR) trial is an ongoing, prospective, multicenter, open-label, non-interventional study evaluating RBL’s effectiveness in preventing rCDI recurrence through 8 weeks post-treatment. In the study, 82.9% of patients treated with RBL, experienced no recurrence of C difficile infection, confirming RBL’s effectiveness outside of clinical trials.¹

Study Results

Partial results from the trial were presented at IDWeek. Eligible participants are adults who completed antibiotics for rCDI and are not enrolled in any interventional trials. The study’s primary endpoint measures treatment success—defined as the absence of CDI recurrence within eight weeks.

As of September 18, 2024, 76 patients had received RBL within 30 days of completing antibiotic therapy and completed eight weeks of follow-up. The median patient age was 69 years (range 19–96), and most were female (76.3%) and White (93.4%). Overall, 82.9% (63/76) of participants achieved treatment success (95% CI, 72.5%–90.6%). Among those with an antibiotic washout period longer than 72 hours, success rates were even higher at 87.8%. Consistent treatment success was observed across subgroups stratified by age and previous CDI episodes.

Adverse events (AEs) were reported in 18 patients (23.7%), including six serious AEs (7.9%) and one event of special interest (large bowel obstruction, 1.3%). Only 3 AEs (3.9%) were considered related to RBL, and one death occurred during the study but was deemed unrelated to treatment.

Study investigator, Nicholas Van Hise, PharmD, director, Metro Infectious Disease Consultants, spoke to Contagion, and offered some insights on ROAR and how this might influence clinical decision-making.

Contagion: How do the real-world effectiveness results from the ROAR registry compare with findings from clinical trials of RBL, and what factors might explain any differences observed?

Van Hise: When you look at Rebyota administered in a real-world setting, there are many factors to consider, especially when comparing it to the package insert and the way the clinical trials—primarily PUNCH—were designed to determine effectiveness. In real-world scenarios, you have more flexibility in adjusting the washout period of standard-of-care antibiotics that patients receive for recurrence. You can also modify the time between stopping antibiotics and administering Rebyota.

In contrast, clinical trials are highly regulated. Patients must receive a specific standard-of-care antibiotic for a defined duration, followed by a required washout period, and then Rebyota must be administered at a precise time. In our real-world registry, we observed a much longer washout period than what is typically allowed in clinical trials. This likely allows more residual antibiotics to be eliminated from the colon, which may improve Rebyota engraftment.

As a result, we saw higher Rebyota success rates in the real-world study compared with the clinical trials. Much of this may be due to a better understanding of how Rebyota works and what is needed to achieve high engraftment and establish a new microbiome.

Contagion: Given that most participants in ROAR were older, White, and female, how might these demographic characteristics affect the generalizability of RBL’s safety and effectiveness outcomes to more diverse populations?

Van Hise: I don’t think that the limited diversity in this study will have a major impact on its applicability to other populations. The most important factors influencing the effectiveness of a microbiome replacement product like Rebyota are concomitant comorbidities—such as inflammatory bowel disease—and other risk factors that increase the likelihood of failure, including recurrent antibiotic use and the need for additional antibiotics after Rebyota administration. These are the key determinants of success.

We have seen strong outcomes across all adult demographic groups (18 years of age and older) in which Rebyota has been used, so demographics alone should not present a significant issue.

Contagion: How might the ROAR findings influence clinical decision-making and antibiotic stewardship strategies for preventing recurrent C. difficile infection in routine care settings?

Van Hise: This is an exciting development when we think about how Rebyota could impact the long-term management of patients with recurrent C. difficile infection (CDI). Once patients enter the cycle of recurrent CDI, they face a very high risk of another episode within 30 days. That risk can range from as low as 30% to as high as 90% or more after stopping standard-of-care antibiotic therapy.

By breaking that cycle and helping establish a new microbiome through Rebyota, we can reduce hospitalizations, improve patients’ quality of life, and lower healthcare costs. This has a meaningful impact not only on patients themselves, but also on their families and support systems.

It’s also important to consider how this may affect infection control practices. Once C difficile is eradicated and the microbiome is successfully engrafted, an important question is whether patients who later develop diarrhea for other reasons remain infectious. Many studies have not yet examined post-engraftment effects on infection control, but the implications are promising.

Overall, there are many exciting possibilities ahead.

The conversation was edited for grammar and clarity.

Reference
1. Van Hise N, et al. Initial Results From a Real-World Patient Registry Study of Adults Receiving Fecal Microbiota, Live-jslm for the Prevention of Recurrent Clostridioides difficile Infection: The RebyOtA Prospective Registry (ROAR). Presented at IDWeek 2025. October 19-22, 2025. Atlanta, GA.