The American Gastroenterological Association (AGA) has endorsed the use of faecal 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 immune-competent adults with recurrent CDIs should receive faecal microbiota-based therapies on completion of treatment with standard-of-care antibiotics to prevent recurrence, while mildly or moderately immune-compromised adults with recurrent CDIs should undergo conventional faecal microbiota transplant, reported Anne Peery, MD, of the University of North Carolina and colleagues in Gastroenterology.
The panel also recommended that adults hospitalised with severe CDI (defined as a leukocyte count ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL) or fulminant CDI (characterised by shock, ileus, or megacolon) not responding to standard-of-care antibiotics, undergo conventional faecal microbiota transplant.
They said 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 notable was that the guideline panel recommended against treating IBD, including Crohn’s disease, ulcerative colitis and pouchitis, as well as IBS, with faecal 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, told MedPage Today.
The guideline, which not only covered the use of conventional faecal microbiota transplant that uses donor stool delivered via colonoscopy, but also recently FDA-approved therapies likes rectally-administered faecal microbiota live-jslm (Rebyota) and orally-delivered faecal microbiota spores live-brpk (Vowst), provided detailed discussions and visual algorithms to assist in practical clinical decision-making.
“As simple as it sounds – putting diluted 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 faecal 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 said.
The authors also pointed to concerns over the stool donor process used for faecal microbiota-based products, noting that paid donors may have a financial incentive to not accurately represent their current health or risk behaviours, 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 with 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 organisations have already incorporated recommendations about the use of faecal 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 potential indications, even outside CDI”, Kelly said.
Faecal 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 tumours and haematologic malignancies; those who have received chimeric antigen receptor (CAR) T-cell therapy or haematopoietic 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.
Study details
AGA Clinical Practice Guideline on Faecal Microbiota–Based Therapies for Select Gastrointestinal Diseases
Anne Peery, Colleen Kelly, Dina Kao, Aamer Imdad, Osama Altayar,on behalf of the AGA Clinical Guidelines Committee
Published in Gastroenterology in March 2024
Background & Aims
Faecal microbiota–based therapies include conventional faecal microbiota transplant and US Food and Drug Administration–approved therapies, faecal microbiota live-jslm and faecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of faecal microbiota–based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome.
Methods
The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritise clinical questions, identify patient-centred outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of faecal microbiota–based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice.
Results
The guideline panel made seven recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of faecal microbiota–based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional faecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any faecal microbiota–based therapies to prevent recurrent C difficile. In adults hospitalised with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional faecal microbiota transplant. The AGA suggests against the use of conventional faecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials.
Conclusions
Faecal microbiota–based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional faecal microbiota transplant is an adjuvant treatment for select adults hospitalised with severe or fulminant C difficile infection not responding to standard of care antibiotics. Faecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.
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Super poo: The emerging science of stool transplants and designer gut bacteria
Faecal transplantation beats antibiotics for CDI, pharmaceuticals company reports
FDA issues ‘serious risk’ alert on on faecal transplants
The war over faecal microbiota transplants