New Guidelines Recommend Fecal Microbiota Transplant, Related Therapies for Most Patients with Recurrent C Diff

The American Gastroenterological Association (AGA) has released new guidelines on the use of fecal microbiota-based therapies for adults with recurrent Clostridioides difficile infection (CDI).

The AGA says the document, published today in Gastroenterology, is the first comprehensive, evidence-based guideline on the use conventional fecal microbiota transplant (FMT) and FMT-based therapies in recurrent CDI patients. Of the nearly 500,000 Americans who experience CDI each year, an estimated 35% have recurrent infections, and the risk of subsequent recurrence goes up with each case.

While antibiotics are the standard treatment for CDI—a common healthcare-associated condition that causes severe diarrhea and inflammation of the colon—it's become clear that the gut dysbiosis caused by antibiotics plays a role in both the initial infection and recurrent infections. When a patient takes antibiotics for an infection, the drugs target the infecting bacteria but also take out some of the beneficial bacteria in the gut that help keep C difficile in check, which allows the bacterium to flourish and release toxins that cause diarrhea. Taking more antibiotics to treat CDI repeats the cycle, leading to recurrent infections.

Research has shown FMT to be a safe and effective alternative, and several medical societies recommend it for patients with two or more recurrences who have failed antibiotic treatment. The procedure involves the transfer of stool from a healthy donor to the colon of a person with a recurrent CDI to help restore the gut microbiome and prevent further recurrence.

Although FMT is still considered an investigational treatment by the US Food and Drug Administration (FDA), at least 10,000 FMT procedures for recurrent CDI are performed each year. In recent years, the FDA has approved two products that deliver fecal microbiota live-jslm (Rebyota) via enema and fecal microbiota spores live-brpk (Vowst) via oral capsules.

FMT-based therapies recommended for most recurrent CDI patients

Developed by a panel of experts using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework, the AGA guidelines make seven recommendations. The first suggests select use of FMT-based therapies (including conventional FMT, Rebyota, and Vowst) in immunocompetent adults with recurrent CDI after the second recurrence or in select patients with high risk of either recurrent CDI or a morbid CDI recurrence. The therapies should be given upon completion of standard-of-care antibiotics.

In mildly or moderately immunocompromised adults with recurrent CDI, the AGA recommends select use of conventional FMT upon completion of antibiotics. But severely immunocompromised adults with recurrent CDI, such as patients who have neutropenia or have received a bone marrow transplant, are excluded from the recommendation.

The AGA also recommends the use of conventional FMT for adults hospitalized with severe or fulminant (quickly escalating) CDI that's not responding to antibiotic treatment.

But the guideline panel concluded that there is not yet enough evidence supporting the use of FMT in patients with other gastroenterological conditions. For adults with inflammatory bowel diseases (including Crohn's disease, ulcerative colitis, and pouchitis) and irritable bowel syndrome, the guidelines recommend against FMT except in the context of a clinical trial.

The AGA says the guidelines are intended to provide the basis for rational, informed decision-making for patients and healthcare professionals.

"C. diff is debilitating," Amanda Kabage, MS, an FMT researcher and FMT recipient who contributed to the development of the guidelines, said in an AGA press release. "Thanks to this new American Gastroenterological Association guideline, patients will suffer for shorter periods of time and be able to get back to leading happy and healthy lives."