Commercial

Medical Policy

Notification

Fecal Microbiota Transplantation (FMT)

Notification Issued Date:

The policy has been reviewed and reissued to communicate the Company’s continuing position on Fecal Microbiota Transplantation (FMT).

Title:

Fecal Microbiota Transplantation (FMT)

Policy #:

07.05.08d

Policy

FECAL MICROBIOTA TRANSPLANTATION (FMT)

FMT is considered medically necessary and, therefore, covered for treatment of individuals with recurrent Clostridium difficile infection (CDI) when all of the following criteria are met:

Infection confirmed by a positive stool test for C. difficile toxin
There have been at least two recurrences (i.e., three CDI episodes) that are refractory to standard antibiotic treatment (e.g., vancomycin, fidaxomicin, metronidazole).

All other uses for FMT are considered experimental/investigational and therefore not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

REBYOTA (FECAL MICROBIOTA, LIVE-JSLM)

MEDICALLY NECESSARY

A one-time dose of Rebyota (fecal microbiota, live-jslm) for the prevention of CDI is considered medically necessary and, therefore, covered when ALL of the following criteria are met:

The individual is 18 years of age or older
The individual has recurrent CDI with either of the following:

At least two recurrences after a primary episode of CDI (≥3 total CDI episodes) and the individual has completed a full course of standard antibiotic treatment (e.g., vancomycin, fidaxomicin, metronidazole) for the most recent CDI episode
Had at least two episodes of severe CDI resulting in hospitalization within the last year

The individual has a positive stool test for C. difficile toxin within 30 days prior to treatment
Current episode of CDI must be controlled (<3 unformed/loose stools/day for 2 consecutive days)
A single, one-time 150-mL dose will be administered rectally 24 to 72 hours after the last dose of antibiotics.

NOT MEDICALLY NECESSARY

Treatment of CDI with Rebyota (fecal microbiota, live-jslm) is considered not medically necessary.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for Rebyota (fecal microbiota, live-jslm) are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, fecal microbiota transplantation and Rebyota (fecal microbiota, live-jslm) are covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

In 2023, the FDA approved the orally administered fecal microbiota product, Vowst^TM (fecal microbiota spores, live-brpk). Similar to Rebyota, Vowst is approved for the prevention of recurrence of Clostridium difficile infection 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 four capsules by mouth once daily for 3 consecutive days.

On November 30, 2022, the FDA approved Ferring Pharmaceuticals' Rebyota (fecal microbiota, live-jslm) for the prevention of recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age or older, following antibiotic treatment for recurrent CDI. Rebyota is a one-time treatment administered as an enema. Rebyota is not indicated for treatment of CDI.

In 2020, the FDA issued a safety alert regarding the potential risk of serious or life-threatening infections with the use of FMT. Six individuals who received FMT product supplied by a stool bank company based in the United States developed infections caused by enteropathogenic Escherichia coli (EPEC) [two individuals] or Shigatoxin-producing Escherichia coli (STEC) [four individuals]. Four of the six patients required hospitalization.

In 2019, the FDA issued a safety alert regarding the potential risk of serious or life-threatening infections caused by the transmission of multidrug-resistant organisms (MDROs) from the use of FMT. Two immunocompromised individuals developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing E. coli. One of the affected individuals died. FMT used in these two individuals were prepared from stool obtained from the same donor. The donor stool used in each individual's FMT procedures had not been tested for ESBL-producing gram-negative organisms prior to use. Follow-up testing verified donor stool was positive for ESBL-producing E. coli identical to the organisms isolated from the two individuals. Because of these serious adverse events, the FDA has determined that the following additional protections are needed 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 (e.g., healthcare 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 that tests positive for MDROs. At a minimum, tests should include:

extended-spectrum beta-lactamase(ESBL)-producing Enterobacteriaceae
vancomycin-resistant enterococci (VRE)
carbapenem-resistant Enterobacteriaceae (CRE)
methicillin-resistant Staphylococcus aureus (MRSA)

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 2016, the FDA issued updated draft guidance on investigational new drug requirements for the use of FMT to treat CDI not responsive to medication therapy. The draft guidance is similar to the 2013 guidance and states that the FDA is continuing to consider how to regulate FMT and that, during this interim period, the agency will use enforcement discretion regarding the use of fecal transplant to treat treatment-resistant CDI. The FDA requires that physicians obtain adequate informed consent from patients or their legal representative before performing the intervention. The document also noted that selective enforcement does not apply to the use of fecal transplant for treating conditions other than treatment-resistant CDI.

Description

FECAL MICROBIOTA TRANSPLANTATION (FMT)

FMT (also known as fecal bacteriotherapy, fecal transfusion, intestinal microbiota transplantation, probiotic infusion, and donor feces infusion) involves the infusion of a liquid suspension of fecal matter from a healthy donor into an individual with a specific disease. The purpose of this procedure is to re-establish the normal composition of the intestinal flora. FMT is proposed for the treatment of treatment-refractory Clostridium difficile infection (CDI), which can result in mild diarrhea to life-threatening fulminant pseudomembranous colitis.

The major potential clinical application of FMT is the treatment of CDI. Other potential uses of FMT include treatment of conditions in which altered colonic flora may play a role. These include inflammatory bowel disease (IBD), irritable bowel syndrome, idiopathic constipation, and nongastrointestinal disease 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.

Although the efficacy and safety profiles of FMT have not yet been fully evaluated in controlled clinical trials, published data suggest that the use of fecal microbiota to restore intestinal flora may be an effective therapy in the management of refractory CDI.

A 2021 focused update of the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) guideline for 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 (Johnson et. al., 2021). It was the opinion of guideline panelists to have individuals try appropriate antibiotics for at least two recurrences (i.e., three 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 three or more CDI episodes be treated with a vancomycin tapered and pulsed course or fidaxomicin followed by a microbiome-based therapy such as FMT (Poylin et. al., 2021). Per the guideline: “Conventional antibiotic treatment should be used for at least 2 recurrences (i.e., 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 (i.e., third or later CDI episode) to prevent further recurrences (Kelly et. al, 2021). This guideline also specifically recommends a repeat FMT for individuals experiencing a recurrence of CDI within 8 weeks of an initial FMT session.

SYSTEMATIC REVIEWS

Rokkas et al. (2019) performed a systematic review and meta-analysis to assess the efficacy of FMT for the treatment of recurrent CDI. Six randomized controlled trials (RCTs) were included in the analysis (N=348), and seven interventions were compared (donor FMT [dFMT], autologous FMT [aFMT], vancomycin, vancomycin plus dFMT, vancomycin plus bowel lavage, fidaxomicin, and placebo). The primary outcome was the resolution of CDI-related symptoms. The network meta-analysis demonstrated that dFMT was superior to vancomycin (odds ratio [OR], 20.02; 95% credible interval [CrI], 7.05–70.03), vancomycin plus dFMT (OR, 4.69; 95% CrI, 1.04–25.22), vancomycin plus bowel lavage (OR, 22.77; 95% CrI, 4.34 to 131.63), and fidaxomicin (OR, 22.01; 95% CrI, 4.38 to 109.63) groups.

Tariq et al. (2019) performed a systematic review and meta-analysis to assess the efficacy of FMT as a treatment option for recurrent CDI on the basis of results from open-label studies and placebo-controlled clinical trials. The authors were motivated to perform this analysis based on observations that FMT cure rates for CDI are high in observational studies (e.g., >90%) but appear to be consistently lower in open-label studies and clinical trials. Thirteen studies were included for evaluation, including six placebo-controlled RCTs and seven open-label studies. Of 610 individuals receiving FMT, 439 individuals achieved clinical cure (76.1%; 95% confidence interval [CI], 66.4%–85.7%); study heterogeneity was significant (I2=91.35%). Cure rates were found to be lower in randomized trials (139/216, 67.7%; 95% CI, 54.2%–81.3%) versus open-label studies (300/394, 82.7%; 95% CI, 71.1%–94.3%; P<0.001). Subgroup meta-analysis by FMT route of administration indicated lower cure rates with enema than colonoscopy (66.3% vs. 87.4%; P<0.001). However, no differences between colonoscopy and oral delivery routes were detected (87.4% to 81.4%; P=0.17). Lower cure rates were observed for studies that included both recurrent and refractory CDI than those that only included individuals with recurrent CDI (63.9% vs. 79%; P<0.001).

Khan et al. (2018) conducted a systematic review of the literature and meta-analysis of pooled data on the use of FMT as a treatment option for recurrent CDI. Reviewers only selected RCTs comparing FMT (fresh or frozen) with medical treatment. Among the selected studies, there was a nonsignificant trend toward the resolution of diarrhea following a single fresh FMT infusion (nasogastric or nasojejunal tube, upper endoscopy, retention enema, or colonoscopy) compared with frozen FMT infusion or medical treatment (OR, 2.45; 95% CI, 0.78–7.71; P=0.12, I2=69%), but different forms and routes of FMT administration were shown to be equally efficacious. Reviewers concluded that FMT is a promising treatment modality for recurrent CDI. Variability of FMT dose usages, small trial populations, and window to assess treatment success or failure limited analysis data.

Quraishi et al. (2017) published a systematic review and meta-analysis of studies (including RCTs) investigating the effect of FMT in individuals with recurrent or refractory CDI. Reviewers deemed the RCTs as having a low risk of bias (including adequate randomization with allocation concealment and intention-to-treat analysis). Reviewers did not report an assessment of bias in terms of blinding, sample size adequacy, or possible differences in baseline characteristics. They argued that none of the trials examining the efficacy of FMT were truly placebo-controlled, and the case series followed individuals until resolution of CDI (range, 10 weeks to 8 years), although some had an incomplete follow-up. In the pooled analysis, 92% of individuals had a resolution of CDI (95% CI, 89%–94%); heterogeneity was classified as likely moderate (I2=59%). Additionally, in the seven trials that evaluated FMT, the intervention overall was associated with an increase in the resolution of recurrent and refractory CDI (relative risk [RR], 0.23; 95% CI, 0.07–0.80). The 30 case series reported resolution rates for CDI ranging from 68% to 100%.

The Quraishi et al. (2017) review found FMT to be effective in the treatment of recurrent and refractory CDI, and no serious adverse events from FMT were reported in the RCTs through the follow-up period. Most adverse effects in the case series were minor (bloating, belching, abdominal cramps, pain or discomfort, nausea, vomiting, excess flatulence, constipation, transient fever, urinary tract infections, self-limiting diarrhea, irregular bowel movement). However, reviewers noted several limitations. Based on variability in the definitions of CDI resolution used across the studies, reviewers could not distinguish between recurrent and refractory CDI. There were also variations across studies in terms of recipient preparations, number of infusions, time to resolution, follow-up, overall response, dosing, concurrent use of medications, and other nonspecified biases. Heterogeneity among studies was considerable.

Prior to the availability of RCTs in this area, several systematic reviews of uncontrolled studies on FMT for treating CDI were also published (Guo et al., 2012; Sofi et al., 2013; Drekonja et al., 2015; Chapman et al., 2016). Overall, data from these uncontrolled studies have reported high rates of resolution of recurrent CDI following treatment with FMT.

RETROSPECTIVE STUDIES

To investigate the long-term clinical outcomes of FMT in individuals with CDI, Mamo et al. (2018) conducted a retrospective study using a follow-up survey of 137 individuals who had received FMT for recurrent CDI at a single-center between January 2012 and December 2016. Median time from last FMT to follow-up was 22 months. Overall at follow-up, 82% (113/137) of individuals had no recurrence of CDI (nonrecurrent CDI group) and 18% (24/137) of individuals had CDI (recurrent CDI group). The survey results suggested that antibiotic exposure for non-CDI infections after FMT were more common in the recurrent CDI group (75%) than in the nonrecurrent CDI group (38%; P<.001). Overall, 82% of individuals reported being symptom-free.

To characterize a pediatric population with recurrent CDI, Alrdich et al. (2018) published a retrospective study that included both hospital-acquired CDI and community-acquired CDI cases, comparing the success rates of various treatments used including FMT. The pediatric population consisted of 175 subjects ages 1 to 21 years reporting 215 separate CDI episodes. Treatments included oral metronidazole (145/207 [70%]) and oral vancomycin (30/207 [15%]), with recurrent rates of 30% (42/145) and 37% (11/30), respectively. Overall, 29% (63/215) of all CDI cases had at least one documented recurrence. Using multivariate analysis, the study showed that subjects with hospital-acquired CDI were 2.6 times less likely to recur than those with community-acquired CDI (OR, 0.39; 95% CI, 0.18–0.85; P=0.018) and that FMT had an overall success rate of 83% (10/12).

In another retrospective study, Meighani et al. (2017) assessed outcomes from FMT for recurrent CDI in individuals with IBD. All individuals underwent FMT between December 2012 and May 2014 within a single healthcare system. Demographic and clinical characteristics, as well as treatment outcomes for individuals with IBD, were compared with those of the general population within this system. Of 201 individuals who underwent FMT, 20 had concurrent IBD, and the study found that the response to FMT and CDI relapse rate in the IBD group (n=20) did not differ statistically from the rest of the cohort (n=201). The overall response rate in the IBD population was 75% at 12 weeks. Study design, lack of a standardized FMT treatment protocol, and variable donors limit certainty in conclusions drawn from these data.

PRACTICE GUIDELINES AND POSITION STATEMENTS

American College of Gastroenterology

In 2019, the American College of Gastroenterology (ACG) published guidelines on the management of adult individuals with ulcerative colitis (UC) (Rubin et al., 2019). The guidelines noted that "fecal microbiota transplantation (FMT) requires more study and clarification of treatment before use as therapy for UC."

In 2021, the ACG published a guideline on the management of CDI (Kelly et. al., 2021). This guideline makes the following recommendations:

"We suggest fecal microbiota transplantation (FMT) be considered for individuals with severe and fulminant CDI refractory to antibiotic therapy, particularly, when individuals are deemed poor surgical candidates (strong recommendation, low quality of evidence)."
"We recommend patients experiencing their second or further recurrence of CDI be treated with FMT to prevent further recurrences (strong recommendation, moderate quality of evidence)."
"We recommend FMT be delivered through colonoscopy (strong recommendation, moderate quality of evidence) or capsules (strong recommendation, moderate quality of evidence) for treatment of CDI; we suggest delivery by enema if other methods are unavailable (conditional recommendation, low quality of evidence)."
"We suggest repeat FMT for patients experiencing a recurrence of CDI within 8 weeks of an initial FMT (conditional recommendation, very low quality of evidence)."
"FMT should be considered for recurrent CDI in patients with IBD (strong recommendation, very low quality of evidence)."

In 2021, the ACG also published a guideline on the management of irritable bowel syndrome (IBS) (Lacy et al., 2021). This guideline recommended against the use of fecal transplant for the treatment of global IBS symptoms (strong recommendation; very low quality of evidence).

American Society of Colon and Rectal Surgeons

In 2021, the American Society of Colon and Rectal Surgeons (ASCRS) published a guideline on the management of CDI (Poylin et. al., 2021). This guideline states that:

"Patients with recurrent or refractory CDI should typically be considered for fecal bacteriotherapy (e.g., intestinal microbiota transplantation) if conventional measures, including appropriate antibiotic treatment, have failed (Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B)."
"Patients with 3 or more CDI episodes can be managed with a vancomycin tapered and pulsed course or fidaxomicin followed by a microbiome-based therapy such as fecal microbiota transplantation."
"In general, conventional antibiotic treatment should be used for at least 2 recurrences (i.e., 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.”

Infectious Diseases Society of America and Society for Healthcare Epidemiology of America

In 2017, McDonald et al. published the 2017 updated guidelines by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) for CDI in adults and children. The guidelines state 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 two recurrences (i.e., three CDI episodes) before FMT is considered. The optimal timing between multiple FMT sessions is not discussed in the guidelines. Per these guidelines, a recurrent case occurs within 2 to 8 weeks of the incident case and requires both clinical plus laboratory evidence of disease for diagnosis.

A 2021 focused update of this guideline echoes the previous recommendations for FMT by stating: "FMT is recommended only for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments and where appropriate screening of donor and donor fecal specimens have been performed, in accordance with these newer FDA recommendations." (Johnson et. al., 2021)

US FOOD AND DRUG ADMINISTRATION (FDA) GUIDANCE

In July 2013, the FDA issued guidance regarding investigational new drug requirements for use of FMT to treat CDI not responsive to standard therapies. The document states that the FDA is continuing to consider how to regulate FMT and that, during this interim period, the agency will use enforcement discretion regarding use of FMT to treat treatment-resistant CDI infections. The FDA requires that providers obtain adequate informed consent from individuals or their legal representative before performing the intervention. The document also states that selective enforcement does not apply to other uses of FMT, and that data regarding the use of FMT to treat conditions other than treatment-resistant C. difficile are limited. Furthermore, the study of FMT for these other uses is not included in the FDA enforcement policy.

In 2016, the FDA issued updated draft guidance on investigational new drug requirements for the use of FMT to treat CDI not responsive to medication therapy. The draft guidance is similar to the 2013 guidance and states that the FDA is continuing to consider how to regulate FMT and that, during this interim period, the agency will use enforcement discretion regarding the use of fecal transplant to treat treatment-resistant CDI. The FDA requires that physicians obtain adequate informed consent from individuals or their legal representative before performing the intervention. 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 potential risk of serious or life-threatening infections caused by the transmission of multidrug-resistant organisms (MDROs) from the use of FMT. Two immunocompromised individuals developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli). One of the affected individuals died. FMT used in these two individuals were prepared from stool obtained from the same donor. The donor stool used in each individual's FMT procedures had not been tested for ESBL-producing gram-negative organisms prior to use. Follow-up testing verified donor stool was positive for ESBL-producing E. coli identical to the organisms isolated from the two individuals. Because of these serious adverse events, the FDA has determined that the following additional protections are needed 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 (e.g., healthcare 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 that tests positive for MDROs. At a minimum, tests should include:

extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
vancomycin-resistant enterococci (VRE)
carbapenem-resistant Enterobacteriaceae (CRE)
methicillin-resistant Staphylococcus aureus (MRSA)

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 2020, the FDA issued a safety alert regarding the potential risk of serious or life-threatening infections with the use of FMT. Six individuals who received FMT product supplied by a stool bank company based in the United States developed infections caused by enteropathogenic E. coli (EPEC) [two individuals] or Shigatoxin-producing E. coli (STEC) [four individuals]. Four of the six individuals required hospitalization.

REBYOTA (FECAL MICROBIOTA, LIVE-JSLM)

Rebyota (fecal microbiota, live-jslm; Ferring Pharmaceuticals, Inc.) is a live biotherapeutic suspension consisting of a broad consortium of microbes prepared from human stool for rectal use for reduction of recurrent CDI infection (Khanna et al., 2022). Rebyota was FDA-approved in November 2022 for the prevention of recurrence of CDI in individuals 18 years of age and older, following antibiotic treatment for recurrent CDI. Rebyota is not indicated for the treatment of CDI. Rebyota is indicated as a single dose of 150 mL administered rectally 24 to 72 hours after the last dose of antibiotics for CDI. The most commonly reported (3% or more) adverse reactions occurring in adults following a single dose of Rebyota were abdominal pain (8.9%), diarrhea (7.2%), abdominal distention (3.9%), flatulence (3.3%), and nausea (3.3%).

The FDA approval was based on results from the "clinical program including the randomized, double-blind, placebo-controlled Phase 3 PUNCH CD3 trial in which a single dose of Rebyota demonstrated superiority to placebo as a treatment to reduce recurrence of CDI after standard-of-care antibiotic treatment. Two hundred sixty-two (262) trial participants received blinded treatment [Rebyota, n=177; placebo, n=85] and the primary endpoint was treatment success, defined as the absence of CDI diarrhea within 8 weeks after completing study treatment. The Bayesian model-estimated treatment success rate at eight weeks for Rebyota was 70.6% versus 57.5% for placebo, with a 99.1% posterior probability that Rebyota was superior to placebo in reducing recurrent CDI after standard-of-care antibiotic treatment. More than 90% of study participants who achieved treatment success remained free of CDI recurrence through six months" (Ferring Pharmaceuticals, 2022a).

Khanna et al. (2022) conducted a prospective, multicenter, randomized, double-blind, placebo-controlled, phase III study, with a Bayesian primary analysis integrating data from a previous phase IIb study, to evaluate the safety and efficacy of RBX2660 (Rebyota) for the prevention of recurrent CDI. Adults who had one or more CDI recurrences with a positive stool assay for C. difficile and who were previously treated with standard-of-care antibiotics were randomly assigned 2:1 to receive a subsequent blinded, single-dose enema of RBX2660 or placebo. The primary endpoint was treatment success, defined as the absence of CDI diarrhea within 8 weeks of study treatment. Two hundred eighty-nine (289) individuals were randomly assigned and 267 received blinded treatment (n = 180, RBX2660; n = 87, placebo). Original model estimates of treatment success were 70.4% versus 58.1% with RBX2660 and placebo, respectively. However, after aligning the data to improve the exchangeability and interpretability of the Bayesian analysis, the model-estimated treatment success rate was 70.6% with RBX2660 versus 57.5% with placebo, with an estimated treatment effect of 13.1% and a posterior probability of superiority of 0.991. More than 90% of the participants who achieved treatment success at 8 weeks had sustained response through 6 months in both the RBX2660 and the placebo groups. Overall, RBX2660 was well tolerated, with manageable adverse events. The incidence of treatment-emergent adverse events was higher in RBX2660 recipients compared with placebo and was mostly driven by a higher incidence of mild gastrointestinal events. The authors concluded that RBX2660 is a safe and effective treatment to reduce recurrent CDI following standard-of-care antibiotics with a sustained response through 6 months.

References

Aldrich AM, Argo T, Koehler TJ, et al. Analysis of treatment outcomes for recurrent Clostridium difficile infections and fecal microbiota transplantation in a pediatric hospital. Pediatr Infect Dis J. 2019;38(1):32-36.

American College of Gastroenterology (ACG). ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. [The American Journal of Gastroenterology Web site]. June 2021. Available at: https://journals.lww.com/ajg/Fulltext/2021/06000/ACG_Clinical_Guidelines__Prevention,_Diagnosis,.12.aspx. Accessed April 25, 2025.

Anderson JL, Edney RJ, Whelan K. Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Aliment Pharmacol Ther. 2012;36(6):503-516.

Aziz I, Törnblom H, Palsson OS et al. How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors. Am J Gastroenterol. 2018;113(7):1017-1025.

Baddour LM. Donor feces for recurrent Clostridium difficile infection. N Engl J Med. 2013;Jan 16.

Bakken JS. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Anaerobe. 2009;15(6):285-289.

Bar-Yoseph H, Carasso S, Shklar S, et al. Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective. Clin Infect Dis. 2021;73(1):e166-e175.

Brandt LJ, Reddy SS. Fecal microbiota transplantation for recurrent clostridium difficile infection. J Clin Gastroenterol. 2011;45 Suppl:S159-S167.

Chapman BC, Moore HB, Overbey DM, et al. Fecal microbiota transplant in patients with Clostridium difficile infection: A systematic review. J Trauma Acute Care Surg. 2016;81(4):756-764.

Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431-455.

Cold F, Kousgaard SJ, Halkjaer SI, et al. Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review. Microorganisms. Sep 18 2020;8(9).

Costello SP, Hughes PA, Waters O et al. Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial. JAMA. 2019;321(2).

Crothers JW, Chu ND, Nguyen LTT, et al. Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study. BMC Gastroenterol. 2021;21(1):281.

Drekonja D, Reich J, Gezahegn S, et al. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Ann Intern Med. 2015;162(9):630-638.

Du C, Luo Y, Walsh S, et al. Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis. J Clin Gastroenterol. 2021;55(4):300-308.

Dubberke ER, et al. Results from a randomized, placebo-controlled clinical trial of a RBX2660- a microbiota-based drug for the prevention of recurrent Clostridium difficile Infection. Clin Infect Dis. 2018;67(8):1198-1204.

Elhusein AM, Fadlalmola HA. Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome Patients: An Updated Systematic Review and Meta-Analysis. Gastroenterol Nurs. 2022;45(1):11-20.

Fang H, Fu L, Li X, et al. Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study. Microb Cell Fact. 2021;20(1):18.

Fehily SR, Basnayake C, Wright EK, et al. Fecal microbiota transplantation therapy in Crohn's disease: Systematic review. J Gastroenterol Hepatol. 2021;36(10):2672-2686.

Ferring Pharmaceuticals, Inc. Ferring receives U.S. FDA approval for Rebyota (fecal microbiota, live-jslm) - A novel first-in-class microbiota-based live biotherapeutic. Press Release. Parsippany, NJ: Ferring Pharmaceuticals. November 30, 2022.

Ferring Pharmaceuticals, Inc. Rebyota (fecal microbiota, live - jslm) suspension, for rectal use. Prescribing Information. Parsippany, NJ: Ferring Pharmaceuticals; revised November 2022.

Feuerstein JD, Ho EY, Shmidt E, et al. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn's Disease. Gastroenterology. 2021;160(7):2496-2508.

Ford AC, Bercik P, Morgan DG et al. Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care. Gastroenterology. 2013;145(6).

Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53(10):994-1002.

Guo B, Harstall C, Louie T, et al. Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease. Aliment Pharmacol Ther. 2012;35(8):865-875.

Holster S, Lindqvist CM, Repsilber D, et al. The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study. Clin Transl Gastroenterol. 2019;10(4).

Holvoet T, Joossens M, Vazquez-Castellanos JF, et al. Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial. Gastroenterology. 2021;160(1):145-157.e8.

Huttner BD, de Lastours V, Wassenberg M, et al. A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial. Clin Microbiol Infect. 2019;25(7):830-838.

Ianiro G, Eusebi LH, Black CJ, et al. Systematic review with meta-analysis: efficacy of faecal microbiota transplantation for the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2019;50(3):240-248.

Johnsen PH, Hilpüsch F, Cavanagh JP, et al. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol. 2017;3(1).

Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021;73(5):e1029-e1044.

Kachrimanidou M, Malisiovas N. Clostridium difficile infection: a comprehensive review. Crit Rev Microbiol. 2011;37(3):178-187.

Karjalainen EK, Renkonen-Sinisalo L, Satokari R, et al. Fecal Microbiota Transplantation in Chronic Pouchitis: A Randomized, Parallel, Double-Blinded Clinical Trial. Inflamm Bowel Dis. 2021;27(11):1766-1772.

Kelly CP. Fecal microbiota transplantation - An old therapy comes of age. N Engl J Med. 2013;368(5):474-475.

Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2021;116(6):1124-1147.

Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165(9):609-616.

Khan MY, Dirweesh A, Khurshid T, et al. Comparing fecal microbiota transplantation to standard-of-care treatment for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018;30(11):1309-1317.

Khanna S, Assi M, Lee C, et al. Efficacy and safety of RBX2660 in PUNCH CD3, a phase III, randomized, double-blind, placebo-controlled trial with a Bayesian primary analysis for the prevention of recurrent Clostridioides difficile infection. Drugs. 2022;82(15):1527-1538 [published correction appears in Drugs. 2022;82(15):1539].

Kwak S, Choi JH, Hink T, et al. Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial. Microbiome. 2020;8(1):125.

Lacy BE, Pimentel M, Brenner DM, et al. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol. 2021;116(1):17-44.

Lahtinen P, Jalanka J, Hartikainen A, et al. Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome. Aliment Pharmacol Ther. 2020;51(12):1321-1331.

Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68(Suppl 3):s1-s106.

Langdon A, et al. Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study. Genome Med. 2021;13(1):28.

Lee CH, Belanger JE, Kassam Z, et al. The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema. Eur J Clin Microbiol Infect Dis. 2014;33(8):1425-1428.

Lee CH, Chai J, Hammond K, et al. Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure. Eur J Clin Microbiol Infect Dis. 2019;38(9):1731-1735.

Lee CH, Steiner T, Petrof EO, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile Infection: a randomized clinical trial. JAMA. 2016;315(2):142-149.

Li Q, Ding X, Liu K, et al. Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes. Clin Transl Gastroenterol. 2020;11(8):e00224.

Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2018;113(4):481-517.

Madsen AMA, Halkjaer SI, Christensen AH, et al. The effect of faecal microbiota transplantation on abdominal pain, stool frequency, and stool form in patients with moderate-to-severe irritable bowel syndrome: results from a randomised, double-blind, placebo-controlled study. Scand J Gastroenterol. 2021;56(7):761-769.

Mamo Y, Woodworth MH, Wang T, et al. Durability and long-term clinical outcomes of fecal microbiota transplant treatment in patients with recurrent Clostridium difficile infection. Clin Infect Dis. 2018;66(11):1705-1711.

McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48.

Meighani A, Alimirah M, Ramesh M, et al. Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease. Int J Hepatol. 2020;2020:1874570.

Meighani A, Hart BR, Bourgi K, et al. Outcomes of fecal microbiota transplantation for Clostridium difficile infection in patients with inflammatory bowel disease. Dig Dis Sci. 2017;62(10):2870-2875.

Moayyedi P, Surette MG, Kim PT, et al. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015;149(1):102-109 e106.

Nelson RL, Kelsey P, Leeman H, et al. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2011(9):CD004610.

Orenstein R, Dubberke ER, Khanna S, et al. Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial. BMC Infect Dis. 2022;22(1):245.

Orenstein R, Dubberke E, Hardi R, et al. Safety and durability of RBX2660 (microbiota suspension) for recurrent Clostridium difficile infection: Results of the PUNCH CD Study. Clin Infect Dis. 2016;62(5):596-602.

Paramsothy S, Paramsothy R, Rubin DT, et al. Faecal microbiota transplantation for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2017;11(10):1180-1199.

Petrof EO, Gloor GB, Vanner SJ, et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut. Microbiome. 2013;1(1):3.

Poylin V, Hawkins AT, Bhama AR, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Clostridioides difficile Infection. Dis Colon Rectum. 2021;64(6):650-668.

Proenca IM, Allegretti JR, Bernardo WM, et al. Fecal microbiota transplantation improves metabolic syndrome parameters: systematic review with meta-analysis based on randomized clinical trials. Nutr Res. 2020;83:1-14.

Quraishi MN, Widlak M, Bhala N, et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther. 2017;46(5):479-493.

Ramai D, Zakhia K, Fields PJ, et al. Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2021;66(2):369-380.

Rokkas T, Gisbert JP, Gasbarrini A, et al. A network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent Clostridium difficile infection. United European Gastroenterol J. 2019;7(8):1051-1063.

Rossen NG, Fuentes S, van der Spek MJ, et al. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015;149(1):110-118 e114.

Rossen NG, MacDonald JK, de Vries EM, et al. Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. World J Gastroenterol. 2015;21(17):5359-5371.

Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol. 2019;114(3):384-413.

Saha S, Tariq R, Tosh PK, et al. Faecal microbiota transplantation for eradicating carriage of multidrug-resistant organisms: a systematic review. Clin Microbiol Infect. 2019;25(8):958-963.

Seong H, Lee SK, Cheon JH, et al. Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction. J Infect. 2020;81(5):719-725.

Sha S, Liang J, Chen M, et al. Systematic review: faecal microbiota transplantation therapy for digestive and nondigestive disorders in adults and children. Aliment Pharmacol Ther. 2014;39(10):1003-1032.

Sofi AA, Silverman AL, Khuder S, et al. Relationship of symptom duration and fecal bacteriotherapy in Clostridium difficile infection-pooled data analysis and a systematic review. Scand J Gastroenterol. 2013;48(3):266-273.

Sokol H, Landman C, Seksik P, et al. Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study. Microbiome. 2020;8(1):12.

Sood A, Mahajan R, Singh A, et al. Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients With Ulcerative Colitis: A Pilot Study. J Crohns Colitis. 2019;13(10):1311-1317.

Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478-498;quiz 499.

Tan XY, Xie YJ, Liu XL, et al. A Systematic Review and Meta-Analysis of Randomized Controlled Trials of Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease. Evid Based Complement Alternat Med. 2022;2022:8266793.

Tariq R, Pardi DS, Bartlett MG et al. Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis. Clin Infect Dis. 2019;68(8):1351-1358.

U.S. Food and Drug Administration (FDA). Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies. July 2013. Available online at: https://www.fda.gov/media/86440/download. Accessed April 25, 2025.

U.S. Food and Drug Administration (FDA). FDA Approves First Orally Administered Fecal Microbiota Product for the Prevention of Recurrence of Clostridioides difficile Infection. April 2023. Available online at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-orally-administered-fecal-microbiota-product-prevention-recurrence-clostridioides. Accessed April 25, 2025.

U.S. Food and Drug Administration (FDA). Fecal Microbiota for Transplantation: New Safety Information - Regarding Additional Protections for Screening Donors for COVID-19 and Exposure to SARS-CoV-2 and Testing for SARS-CoV-2. April 2020. Available at: https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota-transplantation-new-safety-information-regarding-additional-protections-screening. Accessed April 25, 2025.

U.S. Food and Drug Administration (FDA). Fecal Microbiota for Transplantation: Safety Alert - Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms. April 2020. Available at: https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota-transplantation-safety-alert-risk-serious-adverse-events-likely-due-transmission. Accessed April 25, 2025.

U.S. Food and Drug Administration (FDA). Guidance for Industry: Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies. November 2022. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-regarding-investigational-new-drug-requirements-use-fecal-microbiota . Accessed April 25, 2025.

van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-415.

Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913-916 e917.

Wang S, Xu M, Wang W, et al. Systematic review: adverse events of fecal microbiota transplantation. PLoS One. 2016;11(8):e0161174.

You DM, Franzos MA, Holman RP. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann Intern Med. 2008;148(8):632-633.

Youngster I, Sauk J, Pindar C, et al. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis. 2014;58(11):1515-1522.

Zhou HY, Guo B, Lufumpa E, et al. Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis. Immunol Invest. 2021;50(4):323-337.

Coding

CPT Procedure Code Number(s)

44705, 0780T

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

A04.71 Enterocolitis due to Clostridium difficile, recurrent

HCPCS Level II Code Number(s)

G0455 Preparation with instillation of fecal microbiota by any method, including assessment of donor specimen

J1440 Fecal microbiota, live - jslm, 1 ml

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 07.05.08d:

05/28/2025	This policy has been reissued in accordance with the Company's annual review process.
7/10/2024	This policy has been reviewed and reissued to communicate the Company’s continuing position on fecal microbiota transplantation (FMT).
07/01/2023	This version of the policy will become effective 07/01/2023. Language was added to the policy section communicating the Company's Medically Necessary coverage position on Rebyota (fecal microbiota, live - jslm). The following HCPCS code has been added to the policy: J1440 Fecal microbiota, live - jslm, 1 ml The following Unlisted code used to represent the instillation of fecal microbiota by oro-nasogastric tube has been removed from the policy: 44799

05/28/2025

This policy has been reissued in accordance with the Company's annual review process.

7/10/2024

This policy has been reviewed and reissued to communicate the Company’s continuing position on fecal microbiota transplantation (FMT).

07/01/2023

This version of the policy will become effective 07/01/2023.

Language was added to the policy section communicating the Company's Medically Necessary coverage position on Rebyota (fecal microbiota, live - jslm).

The following HCPCS code has been added to the policy:

J1440 Fecal microbiota, live - jslm, 1 ml

The following Unlisted code used to represent the instillation of fecal microbiota by oro-nasogastric tube has been removed from the policy: 44799

Revisions From 07.05.08c:

01/01/2023

This policy has been identified for the CPT code update, effective 01/01/2023.

The following CPT Procedure Code has been added to this policy: 0780T

Revisions From 07.05.08b:

06/15/2022

The policy has been reviewed and reissued to communicate the Company’s continuing position on Fecal Microbiota Transplantation (FMT).

05/31/2021

This version of the policy will become effective 05/31/2021.

The following policy criteria have been revised as follows for clarity:

FROM:

Fecal microbiota transplantation (FMT) is considered medically necessary and, therefore, covered for treatment of individuals with recurrent Clostridium difficile infection (CDI) when all of the following criteria are met:

Infection confirmed by a positive stool test for C. difficile toxin;
There have been at least 3 episodes of recurrent infection;
Episodes are refractory to appropriate antibiotic regimens, including at least one regimen of pulsed Vancomycin.

TO:

Fecal microbiota transplantation (FMT), is considered medically necessary and, therefore, covered for treatment of individuals with recurrent Clostridium difficile infection (CDI) when all of the following criteria are met:

Infection confirmed by a positive stool test for C. difficile toxin
There have been at least 2 recurrences (i.e., 3 CDI episodes) that are refractory to standard antibiotic treatment, including at least one regimen of pulsed Vancomycin.

Revisions From 07.05.08a:

11/18/2020	The policy has been reviewed and reissued to communicate the Company’s continuing position on Fecal Microbiota Transplantation (FMT).
11/06/2019	The policy has been reviewed and reissued to communicate the Company’s continuing position on Fecal Microbiota Transplantation (FMT).
07/18/2018	As of 07/18/2018, this policy has been reviewed and reissued to communicate the Company’s continuing position on fecal microbiota transplantation (FMT).

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date:

7/1/2023

Version Issued Date:

7/3/2023

Version Reissued Date:

5/28/2025