Based on the best available evidence and expert consensus, a panel of European, American, and Australian specialists on fecal microbiota transplantation (FMT) established recommendations for both clinical and organizational practices related to stool banking. Their findings were published in the journal Gut.

The panel members performed systematic reviews of the literature focused on the general principles, objectives, and organization of stool banks; selection and screening of donors; collection, preparation, and storage of feces; services and clients; registries, monitoring of outcomes, and ethical issues; and the evolving role of FMT in clinical practice.

Using the Delphi method, they developed statements eliciting expert opinions and considered consensus to have been reached if at least 80% of the respondents agreed with the statement. Final recommendations were graded for suitability according to the Grading of Recommendations Assessment, Development and Evaluation methodology.

General Principles, Objectives, and Organization of Stool Banks

The primary objective of stool banks should be the timely, safe, and traceable provision of FMT to healthcare centers in order to treat Clostridioides difficile infection. While the main goal is standardized collection, storage, and distribution of feces from screened, healthy donors, stool banks may participate in research protocols that follow strict investigative conditions. Furthermore, stool banks are required to follow national regulations to ensure high levels of security for protecting patient/donor data.

The director of the stool bank should have scientific and clinical experience in the field of FMT as either a medical microbiologist, an infectious disease specialist, or a gastroenterologist. The role of the director is to ensure consistent collection, processing, storage, and distribution of material according to regulatory protocols, along with donor-recipient traceback and enforcement of appropriate research conduct where applicable.

To ensure quality management and compliance, the stool bank director should appoint  physicians responsible for coordinating access to the bank from accredited healthcare facilities, evaluating and recruiting stool donors, organizing the processing of feces in the laboratory, and a biobanking expert for the appropriate storage of feces.

The committee should establish protocols for evaluating and approving requests from healthcare facilities, regular reviews of healthcare provider eligibility requirements, and routine analyses of stool bank activities. They should further seek appropriate approval from the relevant national regulatory authorities.

Recommendations for Selecting and Screening Donors

Stool donation must be done voluntarily and donors be informed about the potential risks of donating their feces. Stool banks should explain to potential donors the screening process and take measures to ensure donor confidentiality.

Before beginning the screening process, potential donors must provide written informed consent accepting the screening process and acknowledging the tasks associated with stool donation. Donors should be made aware that they may withdraw their donation at any time. Depending on local regulations regarding tissue or cell donation, donors are permitted to receive reimbursement or compensation.

Recruiting donors can be challenging; to ensure access to FMT material, personnel dedicated to donor operations should use a structured workflow system to recruit and manage donors. Stool banks should target undirected donors, as opposed to patient-selected donors; patient-selected donors can be considered under exceptional circumstances.

In order to minimize risk of transferring infection or traits that can adversely affect the gut microbiome, the screening process includes evaluating the donor’s medical history for infectious diseases, disorders, or treatments that disrupt the balance of gut microbiota. Candidates with a personal history of cancer or systemic autoimmune diseases should be excluded.

Selected donors must undergo clinical assessment, including blood and stool testing, to exclude any potential transmittable diseases; repeat donors must undergo clinical assessment and complete laboratory testing every 8 to 12 weeks. On the day of donation, the panel recommends that donors be assessed for any change in health that might have occurred since screening.

Recommendations for Collection, Preparation, and Storage of Feces

It is recommended that feces be collected on-site at the stool bank using a specific single-use receptacle with a reliable method of identification and traceability, including a unique donor code and the date of collection and processing. Where onsite collection of feces is not possible, the sample should be cooled to 4°C and delivered to the stool bank within 6 hours of collection.

Stool banks must include high-quality microbiological facilities with a biosafety level of at least 2. FMT centers must further ensure the safe processing of human fecal samples by adopting standard operating procedures in compliance with national and international regulations.

Preparation and storage of frozen fecal suspensions should follow the specific steps and formulation for either lower or upper gastrointestinal delivery routes, according to clinician and patient preference. The unique donor code recorded on the fecal suspension container should be further included in the recipient’s records.

Fecal suspensions can be stored for up to 2 years under tightly controlled conditions, and stool banks should ensure that storage processes follow all local, regional, and national regulations. After 2 years, unused FMT materials should be discarded according to national and international procedures for managing medical waste.

Recommendations for Services and Clients

Physicians caring for patients with C difficile infection should be provided access to a stool bank; every FMT delivery requires that the safe administration, documentation, and follow-up be performed under a qualified physician’s direction. It is inappropriate for fecal suspensions to be provided directly to patients.

Recipient centers — be they public or private hospitals or nursing homes — should have an identified physician on staff with specialties related to infectious disease, medical microbiology, or gastroenterology and specific FMT experience.

Recipient centers must carefully document all treatments (procedure reports; patient data; preparation, timing, and administration of FMT material; safety and efficacy outcomes) and proper training of the center’s treatment team.

Stool banks are responsible for educating the recipient center’s treatment team, which must be trained in best FMT practices (such as thawing fecal suspensions, delivery modalities, informed consent, and follow-up). Team members must perform at least 10 FMT procedures to be considered trained.

For sustainability of stool banks, the cost of FMT should be based on a robust business model and requires budget impact analysis that includes subsequent health insurance reimbursement, depending on the country.

Fecal suspensions should remain frozen during transport; stool banks are required to document the release of each sample for its destination. On arrival, the recipient center must confirm and document the identity of each sample as clear traceability is recommended along all steps of the FMT supply chain.

Transported samples should remain frozen upon arrival, and unless a fecal suspension is to be used imminently, it should be transferred immediately to a freezer and kept for no longer than 2 months at -20°C or 2 years at -80°C.

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Recommendations for Registries, Monitoring of Outcomes, and Ethical Issues

According to regulations, an aliquot of each stool sample should be kept frozen for future testing in the case of adverse events. If a stool bank closes, stored samples and related data should be transferred to another stool bank or biobank, and donors should be notified.

FMT practitioners should monitor patients for severe adverse events related to the FMT procedure, such as hospitalization, death, or transmission of infection. Outcomes should be recorded in appropriate recipient registries, which are useful for tracking adverse effects related to treatment as the long-term impact of transferring complex microbial communities is largely unknown.

Donor records, including the donor’s identity and screening results, should also be managed in an official registry regulated by local health authorities. Both donor and recipient records are important in the provision of access to long-term safety data.

Recommendations for the Evolving Role of FMT in Clinical Practice

The panel highly recommends FMT as a treatment for multiply recurrent C difficile infections (defined as 3 or more confirmed episodes or 2 episodes requiring hospitalization). According to several meta-analyses, FMT can achieve a nearly 90% cure rate in recurrent infection of C difficile.

In patients with severe C difficile infection that does not respond to standard treatment, or in patients with a fulminant infection who are unfit for surgery, FMT may be considered as a secondary treatment option or rescue therapy.

Beyond C difficile infection, FMT is indicated to induce remission in mild-to-moderate ulcerative colitis. FMT may further play a role in the treatment of metabolic syndrome, irritable bowel syndrome, hepatic encephalopathy, gut decolonization, primary sclerosing cholangitis, autism, and even cancer, but should be limited to research settings or compassionate use.

Although FMT is considered safe and effective in the treatment of C difficile infection in pediatric patients, the effect of FMT on pregnancy is unknown and should be avoided.

Finally, while data on the short-term efficacy and safety of FMT is plentiful, information on the long-term impact of FMT is still lacking. This concern should be discussed with patients and family and included in the informed consent document.

Disclosure: Multiple authors declare affiliations with the pharmaceutical industry. Please refer to reference for a complete list of authors’ disclosures.

Reference

Cammarota G, Ianiro G, Kelly CR, et al. Internal consensus conference on stool banking for fecal microbiota transplantation in clinical practice [published online September 28, 2019]. Gut. doi:10.1136/gutjnl-2019-319548