Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases

Publication Date: February 20, 2024
Last Updated: April 26, 2024

Summary of Recommendations

In immunocompetent adults with recurrent C difficile infection, the AGA suggests the use of fecal microbiota–based therapies upon completion of standard of care antibiotics over no fecal microbiota–based therapies. (C, L )
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The following considerations are specific to immunocompetent adult patients with nonsevere, nonfulminant recurrent CDI in the outpatient setting:

Diagnosis of recurrent CDI:
  • A CDI diagnosis requires acute-onset, clinically significant, new-onset diarrhea (eg, 3 or more unformed stools in 24 hours) and highly sensitive (nucleic acid amplification or glutamate dehydrogenase) in combination with highly specific (toxin enzyme immunoassay) testing plus improvement of diarrhea with C difficile–directed antibiotics. A positive nucleic acid amplification test alone in the appropriate clinical context is also reasonable for making a CDI diagnosis.
  • Recurrent CDI is typically defined as clinically significant diarrhea with a confirmatory positive test within 8 weeks of completing antibiotics for CDI.
  • In patients who develop recurrent diarrhea after treatment for CDI, it is important to consider not only CDI recurrence, but also alternative diagnoses, especially if there are atypical symptoms, such as diarrhea alternating with constipation or no response in diarrheal symptoms to treatment with vancomycin or fidaxomicin.

When to consider fecal microbiota–based therapies:
  • Fecal microbiota–based therapies include conventional FMT, fecal microbiota live-jslm and fecal microbiota spores live-brpk.
  • Prevention with fecal microbiota–based therapies can be considered in patients after the second recurrence (third episode) of CDI or in select patients at high risk of either recurrent CDI or a morbid CDI recurrence. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities.
  • Careful consideration before proceeding with fecal microbiota–based therapies is recommended in patients who require frequent antibiotics or long-term antibiotic prophylaxis, because ongoing antibiotics may diminish the efficacy of such therapy.

How to administer fecal microbiota–based therapies:
  • Fecal microbiota–based therapies should be given upon completion of a course of standard of care antibiotics for recurrent CDI. The fecal microbiota–based therapies are to prevent recurrence, not for CDI treatment.
  • Suppressive anti-CDI antibiotics (eg, vancomycin) should be used to bridge standard of care antibiotics until fecal microbiota–based therapies are given.
  • Ideally, antibiotics for CDI should be stopped 1–3 days before conventional FMT to allow adequate time for antibiotics to wash out of the system.16 If a bowel purge is given, FMT can be given 1 day after stopping antibiotics. If no bowel purge is given, 3 days off antibiotics is recommended to allow clearance of oral antibiotics. Rarely, patients will recur rapidly (within 1–2 days of stopping CDI antibiotics), this risk needs to be considered when determining an individual treatment window. When administering fecal microbiota spores live-brpk and fecal microbiota live-jslm, refer to the manufacturer package insert for instructions.
  • Conventional FMT should be performed with appropriately screened donor stool.17,18
  • Conventional FMT can be delivered via multiple routes. There is insufficient evidence to recommend a specific route.

Alternatives to fecal microbiota–based therapies:
  • A vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab are reasonable alternative therapies to prevent recurrent CDI in patients who are not interested in fecal microbiota–based therapies.
In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests the use of conventional fecal microbiota transplant upon completion of standard of care antibiotics over no fecal microbiota transplant. (C, VL )
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Mildly or moderately immunocompromised adults are patients who are immunocompromised but do not meet our definition of severe.
  • The implementation considerations for the use of fecal microbiota–based therapies in immunocompetent adults with recurrent CDI can be used in the mildly or moderately immunocompetent population, with the exception of using fecal microbiota spores live-brpk or fecal microbiota live-jslm. There is insufficient evidence to recommend fecal microbiota spores live-brpk or fecal microbiota live-jslm in immunocompromised adult patients with recurrent CDI.
  • Conventional FMT should be performed with appropriately screened donor stool and special testing may be necessary.
In severely immunocompromised adults with recurrent C difficile infection, the AGA suggests against the use of fecal microbiota–based therapies upon completion of standard of care antibiotics over no fecal microbiota–based therapies. (C, VL )
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  • Severely immunocompromised includes patients receiving active cytotoxic therapy for solid tumors and hematologic malignancies, patients who have received chimeric antigen receptor T-cell therapy or hematopoietic cell transplant (only when neutropenic), any neutropenia, patients with severe primary immunodeficiency, patients with advanced or untreated HIV infection (CD4 counts <200/mm3, AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV).
In adults hospitalized with severe or fulminant C difficile infection not responding to antimicrobial therapy, the AGA suggests the use of conventional fecal microbiota transplant over no fecal microbiota transplant. (C, VL )
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The following considerations are specific to adult patients in the hospital with severe or fulminant CDI refractory to standard of care antibiotics.

What is severe or fulminant CDI:
  • Severe CDI is defined as patients with CDI and a leukocyte count ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL.
  • Fulminant CDI presents as severe disease with shock, ileus, or megacolon.

When to consider conventional FMT:
  • Patients with severe or fulminant CDI require multidisciplinary care including critical care, surgery, gastroenterology, and infectious disease.
  • FMT should be considered in hospitalized patients not responding to standard of care antibiotics, generally within 2–5 days after initiating CDI treatment.
  • FMT is not advised in patients with a bowel perforation, obstruction, or those who are severely immunocompromised.

How to administer conventional FMT:
  • FMT should be performed with appropriately screened donor stool. There is no evidence for using the FDA-approved fecal microbiota–based therapies as adjuvant treatment in severe or fulminant CDI.
  • A bowel purge before FMT may not be feasible or safe. In these cases, FMT should be performed without a bowel preparation.
  • First dose of FMT should be delivered via colonoscopy or flexible sigmoidoscopy. Colonoscopy allows the provider to confirm the diagnosis and determine CDI severity. There is insufficient evidence in severe or fulminant CDI for FMT via enema or capsules. Administration of FMT via nasoenteric tube is discouraged, given the increased risk of fecal aspiration.

Follow-up after initial FMT:
  • Treatment response can be assessed by means of monitoring stool output, white blood cell count, and C-reactive protein.
  • Most patients with severe or fulminant CDI will need repeat FMT. The exact timing (generally every 3–5 days) should be based on the patient’s response to treatment, local protocols, and multidisciplinary care. The route of repeated FMT dosing will depend on local expertise and treatment response.80,81
  • Anti-CDI antibiotics may need to be continued after FMT.80, 81, 82 Most published reports resume anti-CDI antibiotics or continue anti-CDI antibiotics when administering FMT.
  • After resolution of colitis, suppressive vancomycin should be continued at discharge and a final fecal microbiota–based therapy performed as an outpatient to prevent CDI recurrence. This treatment for prevention of recurrence can be administered via colonoscopy, capsule, or enema.

Alternatives to FMT:
  • Cases of severe CDI not responding to antibiotics, or fulminant CDI, are often considered for colectomy.
.In adults with ulcerative colitis, the AGA suggests against the use of conventional fecal microbiota transplant, except in the context of clinical trials. (C, VL )
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  • Conventional FMT can reasonably be used in the context of clinical trials and potentially outside a clinical trial in cases of expanded access when no comparable or satisfactory alternative therapy options are available.
  • The recommendation is specific to the use of conventional FMT for the treatment of UC. For patients with recurrent, severe, or fulminant CDI in the settings of UC, please refer to the recommendations of questions 1–3.
In adults with Crohn’s disease, the AGA suggests against the use of conventional fecal microbiota transplant, except in the context of a clinical trial. (C, VL )
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  • The recommendation is specific to the use of conventional FMT for the treatment of CD. For patients with recurrent, severe,I in the settings of CD, please refer to the recommendations of questions 1–3.
In adults with pouchitis, the AGA suggests against the use of conventional fecal microbiota transplant, except in the context of clinical trial. (C, VL )
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The recommendation is specific to the use of conventional FMT for the treatment of pouchitis. For patients with recurrent, severe, or fulminant CDI in the settings of pouchitis, please refer to the recommendations of questions 1–3.
In adults with irritable bowel syndrome, the AGA suggests against the use of conventional fecal microbiota transplant, except in the context of clinical trials. (C, VL )
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  • The recommendation is specific to the use of conventional FMT for the treatment of irritable bowel syndrome. For patients with recurrent, severe, or fulminant CDI in the settings of irritable bowel syndrome, please refer to the recommendations of questions 1–3.

Recommendation Grading

Abbreviations

  • AGA: American Gastroenterological Association
  • CD: Crohn's Disease
  • FMT: Fecal Microbiota Transplantation
  • IBD: Inflammatory Bowel Disease
  • IBS: Irritable Bowel Syndrome
  • UC: Ulcerative Colitis

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases

Authoring Organization

Publication Month/Year

February 20, 2024

Last Updated Month/Year

April 26, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

To present clinical recommendations on the use of fecal microbiota–based therapies in adults with recurrent CDI and conventional FMT in severe to fulminant CDI in the hospital setting, IBDs (ie, CD, UC, and pouchitis), and IBS based on the best available evidence. Fecal microbiota–based therapies include conventional fecal microbiota transplant and US Food and Drug Administration–approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal 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.

Target Patient Population

Adult patients using fecal microbiota–based therapies for recurrent CDI or conventional FMT for severe to fulminant CDI, IBD, and IBS

Target Provider Population

Gastroenterologists and other clinicians caring for adult patients using fecal microbiota–based therapies for recurrent CDI or conventional FMT for severe to fulminant CDI, IBD, and IBS

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D015212 - Inflammatory Bowel Diseases, D016360 - Clostridium difficile, D043183 - Irritable Bowel Syndrome, D000069467 - Fecal Microbiota Transplantation

Keywords

inflammatory bowel disease, ulcerative colitis, Clostridium difficile, Crohn's disease, IBD, IBS, C diff, pouchitis, Fecal Microbiota Transplant, FMT, C Difficile Infection, irritable bowel syndrome

Source Citation

Anne F. Peery, Colleen R. Kelly, Dina Kao, Byron P. Vaughn, Benjamin Lebwohl, Siddharth Singh, Aamer Imdad, Osama Altayar, AGA Clinical Practice Guideline on Fecal Microbiota–Based Therapies for Select Gastrointestinal Diseases, Gastroenterology, Volume 166, Issue 3, 2024, Pages 409-434, ISSN 0016-5085, https://doi.org/10.1053/j.gastro.2024.01.008.

Supplemental Methodology Resources

Data Supplement