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A.2.01.92
Fecal microbiota transplantation (FMT) involves the administration of intestinal microorganisms via the transfer of stool from a healthy person into a diseased individual, with the intent of restoring normal intestinal flora. Fecal transplant is proposed for treatment-refractory Clostridioides (formerly Clostridium) difficile infection (CDI) and other conditions, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), pouchitis, constipation, multi-drug resistant organism (MDRO) infection, or metabolic syndrome.
Fecal Microbiota
Fecal microbiota transplantation (FMT), also called donor feces infusion, intestinal microbiota transplantation, and fecal bacteriotherapy, involves the duodenal infusion of intestinal microorganisms via the transfer of stool from a healthy individual into a diseased individual to restore normal intestinal flora. The stool can be infused as a liquid suspension into a patient’s upper gastrointestinal tract though a nasogastric tube or gastroscopy, into the colon through a colonoscope or rectal catheter, or administered orally via capsules (ie, encapsulated FMT). Traditionally, the material used for FMT was prepared either within hospital facilities or at stool banks. More recently, FDA-approved FMT therapies have also come onto the market.
The goal of FMT is to replace damaged and/or disordered native microbiota with a stable community of donor microorganisms. The treatment is based on the premise that an imbalance in the community of microorganisms residing in the gastrointestinal tract (ie, dysbiosis) is associated with specific disease states, including susceptibility to infection.
The human microbiota, defined as the aggregate of microorganisms (bacteria, fungi, archaea) on and in the human body, is believed to consist of approximately 10 to 100 trillion cells, approximately 10 times the number of human cells. Most human microbes reside in the intestinal tract, and most of these are bacteria. In its healthy state, intestinal microbiota performs a variety of useful functions including aiding in the digestion of carbohydrates, mediating the synthesis of certain vitamins, repressing the growth of pathogenic microbes, and stimulating the lymphoid tissue to produce antibodies to pathogens.
Applications
Clostridioides difficile InfectionTo date, the major potential clinical application of FMT is in the treatment of Clostridioides difficile infection (CDI). Infection of the colon with C. difficile is a major cause of colitis and can cause life-threatening conditions including colonic perforation and toxic megacolon. C. difficile occurs naturally in the intestinal flora. According to the 2019 Centers for Disease Control and Prevention (CDC) report, Antibiotic Resistance Threats in the United States, CDI continues to be an urgent threat. In 2017, there were an estimated 223,900 cases of CDI in hospitalized patients and an estimated 12,900 CDI-associated deaths. Interestingly, the overall number of cases of healthcare-associated CDI cases has been trending down since 2012 when the number of cases was estimated at 251,400.
It is unclear what causes C. difficile overgrowth, but disruption of the normal colonic flora and colonization by C. difficile are major components. Disruption of the normal colonic flora occurs most commonly following administration of oral, parenteral, or topical antibiotics. Standard treatment for CDI is antibiotic therapy. However, symptoms recur in up to 35% of patients, and up to 65% of patients with recurrences develop a chronic recurrent pattern of CDI.
Other Applications
Other potential uses of FMT include the treatment of conditions in which altered colonic flora may play a role. They include inflammatory bowel disease, irritable bowel syndrome, idiopathic constipation, and non-gastrointestinal diseases such as multiple sclerosis, obesity, autism, and chronic fatigue syndrome. However, for these conditions, the contribution of alterations in colonic flora to the disorder is uncertain or controversial.
There is interest in alternatives to human feces that might have the same beneficial effects on intestinal microbiota without the risks of disease transmission. A proof of principle study, published in 2013, evaluated a synthetic stool product in two patients with recurrent CDI. The product is made from 33 bacterial isolates developed from culturing stool from a healthy donor.
In 2022, the U.S. Food and Drug Administration (FDA) finalized guidance on investigational new drug (IND) requirements for the use of FMT to treat CDI not responsive to medication therapy. The guidance states that the previous policy of enforcement discretion does not apply to fecal microbiota that is obtained from a stool bank due to safety concerns related to the number of patients that may be exposed to a particular donor and centralized manufacturing practices. As a result, sponsors must comply with IND requirement in these settings. The guidance defines a stool bank as "an establishment that collects, prepares, and stores FMT product for distribution to other establishments, health care providers, or other entities for use in patient therapy or clinical research. An establishment that collects or prepares FMT products solely under the direction of licensed health care providers for the purpose of treating their patients (e.g., a hospital laboratory) is not considered to be a stool bank under this guidance."
The agency will continue to use enforcement discretion regarding the use of fecal transplant to treat treatment-resistant CDI when FMT product is not obtained from a stool bank and where:. 1. physicians obtain adequate informed consent from patients or their legal representative before performing the intervention; 2. providers perform appropriate screening and testing of the stool donor and stool; and 3. procedures that mitigate potential safety concerns of FMT are followed. The document also noted that selective enforcement does not apply to the use of fecal transplant for treating conditions other than treatment-resistant CDI.
In 2019, the FDA issued a safety alert regarding the use of FMT due to the potential risk of serious or life-threatening infections caused by the transmission of multi-drug resistant organisms (MDROs). Two immunocompromised individuals received investigational FMT and developed invasive infections caused by the transmission of extended-spectrum beta-lactamase-producing Escherichia coli. One of the affected individuals died. The donor stool used in each patient's FMT procedures had not been tested for extended-spectrum beta-lactamase-producing gram-negative organisms prior to use. Follow-up testing verified donor stool was positive for MDROs identical to the organisms isolated from the two patients. Due to these events, the FDA has determined that the following additional protections are required for any investigational use of FMT:
Donor screening that specifically addresses risk factors for colonization with MDROs and exclusion of individuals at higher risk of colonization with MDROs (eg, health care workers, persons who have recently been hospitalized or discharged from long-term care facilities, persons who regularly attend outpatient medical or surgical clinics, and persons who have recently engaged in medical tourism).
MDRO testing of donor stool and exclusion of stool testing positive for MDROs. At a minimum, tests should include:
extended-spectrum beta-lactamase-producing Enterobacteriaceae
vancomycin-resistant enterococci
carbapenem-resistant Enterobacteriaceae
methicillin-resistant Staphylococcus aureus
All FMT products currently in storage for future use must be quarantined until donor MDRO carriage risk can be assessed and FMT products are tested and found negative for MDROs.
The informed consent process for FMT treatment subjects should describe the risk of MDRO transmission and infection and the measures being implemented for donor screening and stool testing.
In 2022, the FDA approved the first fecal microbiota product, Rebyota™ (fecal microbiota, live-jslm). Rebyota is approved for the prevention of recurrence of CDI in individuals 18 years of age and older, following antibiotic treatment for recurrent CDI. Importantly, the drug is not approved for the treatment of CDI. Rebyota is supplied as a 150 mL suspension for rectal administration as a single dose, 24 to 72 hours after the last dose of antibiotics for CDI.
In 2023, the FDA approved the first orally administered fecal microbiota product, Vowst™ (fecal microbiota spores, live–brpk). Similar to Rebyota, Vowst is approved for the prevention of recurrence of CDI in individuals 18 years of age and older following antibiotic treatment for recurrent CDI, and is not approved for the treatment of CDI. The drug is administered as 4 capsules by mouth once daily for 3 consecutive days.
Related policies -
Fecal microbiota transplantation using a compounded product (see Policy Guidelines) may be considered medically necessary for the treatment of individuals with recurrent Clostridioides difficile infection under the following condition: (See Policy Guidelines for U.S. Food and Drug Administration Guidance):
There have been at least 2 recurrences that are refractory to standard antibiotic treatment.
Fecal microbiota transplantation is considered investigational in all other situations.
None
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Use of a conventional compounded product refers to an FMT product not involving a stool bank where the FDA exercises enforcement discretion with respect to applicable investigational new drug (IND) requirements. For example, this may include FMT products prepared in a hospital laboratory under the direction of licensed health care providers for the purpose of treating their patients provided that the following requirements are met:
Physicians obtain adequate informed consent from patients or their legal representative before performing the intervention;
Providers perform appropriate screening and testing of the stool donor and stool; and
Procedures that mitigate potential safety concerns of FMT are followed.
There is a lack of consensus on the number of recurrences that warrants consideration of fecal microbiota transplantation (FMT).
The 2024 guidelines from the American Gastroenterological Association (AGA) for fecal microbiota-based therapies include 7 recommendations for the use of FMT in gastrointestinal diseases including Clostridioides difficile infection (CDI). The guidelines consider FMT to be an option for immunocompetent individuals after the second recurrence (third episode). The AGA considers the degree of immunocompromise as a qualifier the use of CD in select individuals at high risk of either recurrent CDI or a morbid CDI recurrence. The AGA defined recurrent CDI as "clinically significant diarrhea with a confirmatory positive test within 8 weeks of completing antibiotics for CDI."
The 2021 focused update of the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) guideline for Clostridioides difficile infection (CDI) states that individuals with multiple recurrences of CDI who have failed to resolve their infection with standard of care antibiotic treatments are potential candidates for FMT. It was the opinion of guideline panelists to have individuals try appropriate antibiotics for at least 2 recurrences (ie, 3 CDI episodes) before FMT is considered. The optimal timing between multiple FMT sessions is not discussed in the guidelines.
The 2021 American Society of Colon and Rectal Surgeons (ASCRS) guideline for CDI recommends that individuals with 3 or more CDI episodes be managed with a vancomycin tapered and pulsed course or fidaxomicin followed by a microbiome-based therapy such as FMT. Per the guideline: “Conventional antibiotic treatment should be used for at least 2 recurrences (ie, 3 CDI episodes) before offering fecal microbiota transplantation." Per Table 3 in this guideline: for "Third or Subsequent” CDI episode: "If FMT is available, then 10-day course of vancomycin followed by FMT.”
The 2021 American College of Gastroenterology (ACG) guideline for CDI recommends FMT for individuals experiencing their second or further recurrence of CDI (ie, third or later CDI episode) to prevent further recurrences. This guideline also specifically recommends a repeat FMT for individuals experiencing a recurrence of CDI within 8 weeks of an initial FMT session.
Per the 2017 IDSA/SHEA guideline, a recurrent case occurs within 2 to 8 weeks of the incident case and requires both clinical plus laboratory evidence of disease for diagnosis; the 2021 IDSA/SHEA guideline does not provide an update to this definition. The 2021 guidelines from the ASCRS and ACG define a recurrent case as one occurring within 8 weeks after the completion of a course of CDI therapy and requiring both clinical plus laboratory evidence of disease for diagnosis.
Due to the potential for serious adverse reactions with FMT, the U.S. Food and Drug Administration (FDA) has determined that the following protections are needed for use of FMT:
Donor screening with questions that specifically address risk factors for colonization with multi-drug resistant organisms (MDROs), and exclusion of individuals at higher risk of colonization with MDROs.
MDRO testing of donor stool and exclusion of stool that tests positive for MDRO. FDA scientists have determined the specific MDRO testing and frequency that should be implemented.
Consent for the use of FMT is obtained from the individual or a legally authorized representative in accordance with FDA guidance.
On April 9, 2020, the FDA published additional safety information regarding the potential risk of transmission of SARS-CoV-2 via FMT. Recommendations for additional screening and testing procedures are outlined in this publication ( https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota-transplantation-new-safety-information-regarding-additional-protections-screening ).
On August 20, 2022, the FDA also published a safety alert regarding the use of FMT and additional safety protections pertaining to the monkeypox virus ( https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/safety-alert-regarding-use-fecal-microbiota-transplantation-and-additional-safety-protections-0 ).
Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:
A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and
B. appropriate with regard to standards of good medical practice; and
C. not solely for the convenience of the Member, his or her Provider; and
D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.
For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
07/17/2014: Approved by Medical Policy Advisory Committee.
08/18/2015: Medical policy revised to add ICD-10 codes.
09/10/2015: Policy reviewed; no changes to policy statements. Policy guidelines section updated to add medically necessary and investigative definitions.
12/21/2015: Policy description updated. Policy statements unchanged.
06/01/2016: Policy number A.2.01.92 added.
12/02/2016: Policy reviewed; no changes.
09/29/2017: Code Reference section updated to add new ICD-10 diagnosis code A04.71, effective 10/01/2017.
01/05/2018: Policy description updated. Policy statements unchanged.
01/04/2019: Policy description updated regarding the FDA's issuance of updated draft guidance on investigational new drug requirements for fecal microbiota transplantation. Policy statements unchanged. Removed deleted ICD-10 diagnosis code A04.7.
12/10/2019: Policy description updated to include FDA safety alert regarding multi-drug resistant organism bacteria in fecal microbiota. Policy statements unchanged.
01/01/2022: Policy description updated regarding Clostridioides difficile infection (CDI) and estimated cases. Policy statement updated to state that fecal microbiota transplantation may be considered medically necessary for the treatment of patients with recurrent Clostridioides difficile infection under the following condition: There have been at least 2 recurrences that are refractory to standard antibiotic treatment. Policy Guidelines updated regarding the 2021 and 2017 CDI guidelines.
12/16/2022: Policy description updated. Policy statement and Policy Guidelines updated to change "patients" to "individuals."
12/20/2022: Code Reference section updated to add new CPT code 0780T, effective 01/01/2023.
04/17/2024: Policy description updated regarding fecal microbiota and FDA guidance on investigational new drug requirements for the use of fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI) not responsive to medication therapy. Added information regarding FMT products. Medically necessary statement revised to state that fecal microbiota transplantation using a compounded product may be considered medically necessary for the treatment of individuals with recurrent CDI under the listed condition. Policy Guidelines updated regarding the use of a compounded product.
02/04/2025: Policy description updated. Policy statements unchanged. Policy Guidelines updated regarding the 2024 guidelines from the American Gastroenterological Association.
Blue Cross and Blue Shield Association Policy # 2.01.92
This may not be a comprehensive list of procedure codes applicable to this policy.
Code Number | Description | ||
CPT-4 | |||
0780T | Instillation of fecal microbiota suspension via rectal enema into lower gastrointestinal tract | ||
44705 | Preparation of fecal microbiota for instillation, including assessment of donor specimen | ||
HCPCS | |||
G0455 | Preparation with instillation of fecal microbiota by any method, including assessment of donor specimen | ||
ICD-9 Procedure | ICD-10 Procedure | ||
ICD-9 Diagnosis | ICD-10 Diagnosis | ||
008.45 | Clostridium difficile | A04.71 | Enterocolitis due to Clostridium difficile, recurrent |
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