Advances in Managing Recurrent C Diff Infection, with Paul Feuerstadt, MD

Recurrent Clostridioides difficile infection has long posed a major clinical challenge, with few effective, durable treatment options and until recently no FDA-approved microbiota-based therapies.

For decades, management revolved around antibiotic courses that often failed to prevent recurrence—leaving patients caught in a debilitating cycle and providers with limited tools. The FDA approval of fecal microbiota, live-jslm (Rebyota) signalled a major shift in the trajectory of C. diff treatment.

“One of the biggest problems with C. difficile is recurrence,” Paul Feuerstadt, MD, a clinical gastroenterologist and an associate clinical professor of medicine at Yale University School of Medicine/PACT-Gastroenterology Center, explained to HCPLive, noting that an estimated 35% of individuals treated with guideline-based treatments will recur.

He goes on to describe how antibiotics only treat part of the infection and do not fully resolve the underlying microbial imbalance. When it comes to addressing recurrence, Feuerstadt references historical approaches with microbiota restoration therapy or fecal microbiota transplant and, more recently, the FDA approval of fecal microbiota, live-jslm.

New data presented at Digestive Disease Week (DDW) 2025 highlight findings from 5 pooled trials of live-jslm, showing a consistent favorable safety profile with similar rates of treatment-emergent adverse events (TEAEs) reported in all live-jslm recipients (70.9%), 1-dose recipients (67.6%), and placebo recipients (60.2%). Most TEAEs were mild or moderate in severity, gastrointestinal in nature, and related to C. diff recurrence and/or preexisting conditions, with few events (<1%) being considered possibly related to live-jslm.1

In a second abstract at DDW, Feuerstadt and colleagues explored the safety and clinical effectiveness of live-jslm when administered by colonoscopy. Physician experiences with the 41 procedures included in the study were largely positive, with 90% of investigators reporting at least a ‘positive’ or ‘very positive’ experience across all aspects of administration. Additionally, material preparation time and ease of passage through the colonoscope were mentioned as reasons for ‘positive’ or ‘very positive’ experiences.2

Of note, among the 39 participants who completed 8-week visits, all (100%) were assessed as either having ‘much improved’ or ‘very much improved’ CGI-I.2

“As we're starting to evolve these FDA approved treatments, RBL is diversifying its data, showing that across 5 trials, including 3 phase 2 trials and 2 phase 3 trials, it's incredibly safe,” said Feuerstadt. “When we apply this knowledge to putting the material through a colonoscope, [we see] that is also safe and effective and a potential modality that can be broadly used.”

Editors’ note: Relevant disclosures for Feuerstadt include Rebiotix Inc, Takeda Pharmaceuticals, Ferring Pharmaceuticals, Seres Therapeutics, and Probiotech.

References

1. Khanna S, Awad T, Guthmueller B, et al. PHYSICIAN EXPERIENCES AND USABILITY OF FECAL MICROBIOTA, LIVE-JSLM (RBL) ADMINISTERED VIA COLONOSCOPY TO ADULTS WITH RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION: ANALYSIS OF A PHASE 3B STUDY. Abstract presented at Digestive Disease Week (DDW) 2025 in San Diego, CA from May 3 - May 6, 2025.

2. Lee C, Feuerstadt P, Louie T, et al. SAFETY OF FECAL MICROBIOTA, LIVE-JSLM, IN ADULTS WITH RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION: AN INTEGRATED SAFETY ANALYSIS FROM 5 PROSPECTIVE CLINICAL TRIALS. Abstract presented at Digestive Disease Week (DDW) 2025 in San Diego, CA from May 3 - May 6, 2025.