AGA Backs Fecal Microbiota-Based Therapies for Recurrent C. Diff

The American Gastroenterological Association (AGA) endorsed the use of fecal microbiota-based therapies for recurrent Clostridioides difficile infections (CDIs) in new guideline recommendations, but advised against such therapies for inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).

The guideline panel first noted that immunocompetent adults with recurrent CDIs should receive fecal microbiota-based therapies upon completion of treatment with standard-of-care antibiotics to prevent recurrence, while mildly or moderately immunocompromised adults with recurrent CDIs should undergo conventional fecal microbiota transplant, reported Anne Peery, MD, of the University of North Carolina at Chapel Hill, and colleagues in Gastroenterology.

The panel also recommended that adults hospitalized with severe CDI (defined as a leukocyte count ≥15 × 10⁹ cells/L and/or creatinine ≥1.5 mg/dL) or fulminant CDI (characterized by shock, ileus, or megacolon) not responding to standard-of-care antibiotics undergo conventional fecal microbiota transplant. They stressed that treatment of severe or fulminant CDIs requires a multidisciplinary approach that includes involvement of the critical care, surgery, gastroenterology, and infectious disease teams.

Perhaps equally as notable was that the guideline panel recommended against treating IBD, including Crohn’s disease, ulcerative colitis, and pouchitis, as well as IBS, with fecal microbiota-based therapies due to a current lack of evidence.

“When patients inquire about use in IBS or IBD, clinicians can refer to these guidelines and explain it is not yet advised,” co-author Colleen Kelly, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, told MedPage Today in an email.

The guideline, which not only covered the use of conventional fecal microbiota transplant that uses donor stool delivered via colonoscopy, but also recently FDA-approved therapies, such as rectally administered fecal microbiota live-jslm (Rebyota) and orally delivered fecal microbiota spores live-brpk (Vowst), provided detailed discussions and visual algorithms to assist in practical clinical decision making.

“As simple as it sounds — putting dilute stool into a person — there are a lot of questions around making the diagnosis of recurrent CDI, what to do with anti-CDI therapies around fecal microbiota transplant, how protocols differ for treatment of recurrent versus acute, severe/fulminant CDI, and how to decide when to use an alternative therapy instead,” Kelly explained.

The authors also pointed to concerns over the stool donor process used for fecal microbiota-based products, noting that paid donors may have a financial incentive to not accurately represent their current health or risk behaviors, similar to concerns raised about paid blood donation.

“Evidence suggests that paid and professional blood donors are more likely to have an infectious disease compared to voluntary donors,” they wrote. “The screening process for these products is not publicly available and how they will adapt to emerging infections is unclear.”

Some international organizations have already incorporated recommendations about the use of fecal microbiota-based therapies into CDI treatment guidelines, but newer products have yet to be included, Peery and colleagues noted. The new guidelines “are more comprehensive, covering all the potential indications, even outside CDI,” Kelly said.

Fecal microbiota transplant is contraindicated in patients with a bowel perforation or obstruction, as well as those who are severely immunocompromised, including patients who are receiving active cytotoxic therapy for solid tumors and hematologic malignancies; those who have received chimeric antigen receptor (CAR) T-cell therapy or hematopoietic cell transplant (only while neutropenic); and those with any neutropenia, severe primary immunodeficiency, or advanced or untreated HIV infection.

Despite the publication of the new guideline, the authors noted that all recommendations are conditional, with low- to very-low-certainty evidence.