Faecal microbiota transplantation for recurrent C. difficile, infections

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Introduction

Faecal microbiota transplantation (FMT) has emerged as a treatment option for C. difficile infection (CDI), the most common nosocomial bacterial infection, which can lead to intestinal damage, sepsis and even death. ^[1],^[2]

While there is evidence that FMT is clinically effective for the treatment of recurrent CDI, there is a limited understanding of the diverse requirements for safe, effective, accessible and sustainable delivery of services.

Purpose

The primary objective of this study was to better understand the key components of FMT provision related to the patient care pathway, the stool donor pathway and the wider healthcare system.

Countries of Focus

This research focused on four high-income countries (Australia, Canada, Italy and the United Kingdom [UK]), which were selected based on geographic variety and having public healthcare systems that are free at the point of service.

Methods

Literature review

• Two PubMed searches were conducted in May 2021. The first search focused on identifying relevant literature from the four countries of interest (Australia, Canada, Italy and the UK) between 2011 and 2021. We also conducted a second search to identify additional literature from other high-income countries to fill knowledge gaps in the four countries of interest. The second search focused on review articles published between 2016 and 2021, to fill gaps in literature on case example countries.
• A web-based grey literature search (June 2021) was also conducted to identify regulations and guidelines for FMT in case example countries.
• In total, 25 papers were included from the literature review and 10 additional papers were included from the grey literature search.

Expert consultations

• In-depth semi-structured interviews were conducted with eight experts across the four countries of interest.
• Three online workshops were conducted in small groups/individually to reflect on learnings from the literature review and interviews.

The Patient Pathway

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Eligibility and referral

• Patients are typically eligible for FMT after a 3rd recurrence of CDI, or a 2nd recurrence in certain high-risk or vulnerable groups
• Patients are often referred for FMT as outpatients, and decisions about eligibility may be made by multidisciplinary clinical teams
• Time from referral to treatment varies from days to weeks and is influenced by the severity of the infection and source of referral (inpatient referrals typically have shorter waiting times)
• Referrals for FMT are also influenced by clinical judgement, clinician awareness of the procedures, location and number of FMT facilities and costs

FMT delivery to patients

• FMT is often delivered by gastrointestinal (GI) or infectious disease specialists
• Delivery modalities include colonoscopy, gastroscopy, enema, nasogastric tube or oral capsule; each has its own risks, for example:
  • Upper GI delivery can lead to aspiration
  • Colonoscopies are invasive and may be more resource intensive
• Availability of delivery modality varies by country based on local regulations, as well as patient factors, clinical expertise and available infrastructure

Patient follow-up

• Post-procedure outpatients are typically monitored for several weeks, and inpatients are monitored as part of routine hospital observations
• Follow-up duration can vary by country, depending on delivery modality and patient characteristics

Stool Donor Pathway

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Recruiting and retaining donors

• Most donors are recruited through existing relationships with the patient or clinician or through general advertising
• In some countries, donors can be anonymous, whereas in others a clinician or patient must identify the donor
• Identification and recruitment of donors is a widescale challenge
  • Often requires the goodwill of individuals
  • Strict regulations on who can donate and whether financial reimbursement is permissible
  • Logistical challenges (e.g. inconvenience, travel and scheduling requirements)

Screening donors and donations

• Donors are screened using health questionnaires and stool and blood tests
• Common exclusion criteria include a positive test for an infectious pathogen, recent antibiotic use or identification of high-risk behaviours for infection
• Only 3% to 20% of potential donors pass screening criteria
• Recommend frequency of screening for repeat donors varies from every few weeks to once a year, and there is lack of guidance on optimal screening frequency

Establishing and running stool banks and preparing faecal material

• Establishing stool banks requires appropriate funding, staff, facilities and equipment
• Stool banks are not universally available, which may limit the ability to provide FMT services
• More evidence is needed for optimal practices with regard to the storage and processing of faecal material to maximise the clinical effectiveness of FMT

Wider Features of Healthcare Systems

The role of regulation and guidelines

• Faecal material for FMT may be classified differently within a given country (e.g., pharmaceutical drug/medicinal product, a biological product or a tissue)
• Classification of the material impacts on how FMT is regulated and by which regulatory body
• Classification as a biological product is often associated with more stringent requirements and legislation for manufacturing
• Processes for licensing, production and transportation of faecal material for FMT also depend on how it is classified

Influences related to cost and reimbursement

• Costs for screening of donors and donations can be a challenge for payers, and may require outsourcing costs
• Establishing donor libraries can be costly
• Payers may not be able to reimburse donors, potentiating issues with recruitment and retention
• When reimbursement is possible, securing public funding and setting up formal billing codes and payment structures are needed, and may not be standardised across localities within a given country

Influences related to capacity for FMT delivery

• Ease of access in some countries is geography dependent, which may require some patients and donors to travel far distances
• Some countries may only have a handful of facilities that provide FMT, resulting in the need to reserve treatment for the most severe cases

Conclusions

The provision of FMT requires more than ensuring that the procedure is safe and efficacious for patients. There are diverse requirements along the patient and donor pathways, as well as wider healthcare system, to successfully deliver FMT.

Key challenges

• Few FMT centres and stool banks available
• Onerous donor screening processes and strict eligibility criteria that limit the number of eligible donors
• Inconvenience of donating and travel requirements
• Classification of FMT and regulatory processes

Key improvement needs

• Improved public awareness, as well as awareness among potential referring healthcare providers (e.g. primary care)
• Increase capacity for delivery of FMT services, especially in regions where there are few or no services available
• More flexible ways of recruiting, screening and retaining donors
• Harmonisation of regulatory policies

Notes

• [1] Patil R.L. 2013. 'Proton Pump Inhibitors and Clostridium difficile Infection: Are we Propagating an Already Rapidly Growing Healthcare Problem?' Gastroenterology Research 6(5):171–3. doi: 10.4021/gr575w
• [2] Guery B., T. Galperine & F. Barbut. 2019. 'Clostridioides Difficile: Diagnosis and Treatments.' BMJ. 366:1–19. l4609. doi: 10.1136/bmj.l4609

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Topics

• Australia
• Canada
• France
• Gastrointestinal Disorders
• Health Care Delivery Approaches
• Infectious Diseases
• Italy
• United Kingdom