For patients with persistent C.Diff infection this relatively novel, evidence-based treatment is providing a cure. Logistics and supply have hampered adoption, but the AHSN has helped to solve this issue and increase rates of use by creating a faecal microbiota transplantation (FMT) bank.

“Before the procedure I had a large burden of anxiety about the ongoing diarrhoea and I could not even do my cooking.  Now (after the faecal transplant) the diarrhoea has gone and I am so happy.”

Patient

“The diarrhoea was taking a huge psychological toll on my father and it meant he could not visit his wife in her care home.  Since the diarrhoea resolved, as a result of the faecal transplant, he has been able to visit her. I believe that were it not for the procedure, he would no longer be with us.”

Patient family member

What was the problem?

Clostridium difficile (C.diff) is a bacterium that lives harmlessly in the gut of approximately 3% of healthy people. The use of broad-spectrum antibiotics and immunosuppressive agents can alter the balance of bacteria within the gut, resulting in an overgrowth of C.diff and C. diff infection (CDI).

CDI has a huge impact on the quality of life for patients; it causes chronic diarrhoea, abdominal pain, bloating, gut dysfunction, and it can be fatal. These symptoms can persist for months to years. Individuals with CDI often find they cannot live their normal life, they struggle with typical activities, have reduced mobility, are in chronic pain, and can become anxious, and socially reclusive. This is a disease that affects both the physical and mental wellbeing of patients.

CDI is common, and is reported as the underlying cause of death for around 2,500 patients a year in England and Wales, and a contributing factor in a further 3,200 deaths a year. The one year all-cause mortality rate for CDI cases is 37%. The
costs per CDI case are between £ 5,000-10,000. This is mainly due to prolonged hospital stays (the average length being 27 days) and high re-admission rates, as patients with a first episode of CDI have a 22% chance of developing chronic CDI.

The current treatment for chronic CDI is a course of targeted antibiotics, usually taken for 14 day or six weeks. Often these patients do respond while on treatment, but 69% symptoms return once the antibiotic are stopped, and these patients can end up on antibiotics indefinitely.

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What we did and why

Faecal microbiota transplantation (FMT) is a procedure suitable for patients with recurrent CDI, approved by the National Institute for Health and Clinical Excellence (NICE).

An FMT is the provision of a screened, specially prepared healthy donor stool, which is placed into the small intestine of a patient via a nasal tube. The procedure restores the balance of bacteria (flora) within the gut, replacing the diseased flora of the patient with healthy donor flora. This means the overgrowth of C. Diff is suppressed, leading to the patient’s symptoms resolving, and them being cured within days of the procedure.

FMT is a very effective treatment for CDI, with an overall cure rate of 94% compared to 31% for standard antibiotic therapy (Van Nood E et al, 2013), and minimal side-effects. FMT has increased efficacy and reduced cost when compared to other options, but despite this it is not a widely used treatment across the UK. A survey of clinicians around the country shows that they are aware of the technique, and willing to use it, but provision is hampered by logistics and a lack of technical and clinical expertise (Porter and Fogg, 2015).

In July 2015 the Wessex Academic Health Science Network (AHSN) supported the setup of a Faecal Microbiota Transplant (FMT) service in Portsmouth through the Innovation and Wealth Creation Accelerator Fund. The Wessex Faecal Microbiota Service based within the Microbiology Department at Portsmouth Hospitals NHS Trust (PHT) is an innovative pilot service providing frozen FMTs for the treatment of recurrent C Diff infection.

The implementation of the FMT service ensures patients have access the best treatment and outcomes. It provides the region with a centre of excellence and access to a fully functional FMT bank; overcoming the logistical and expertise issues which have hampered use past of FMT by clinicians.

PHT has pioneered FMT in the region, developing local protocols building regional relationships, and treating patients. As the only provider of FMT currently within the region, PHT holds the most clinical, technical and logistical experience.

The FMT service includes the donor screening and selection, processing of donor stool into frozen FMT aliquots, quality procedure to ensure donations are safe for use, storage and transport of aliquots, assessing patients in clinic to determine suitability for an FMT, providing FMT as an elective inpatient procedure, providing local expertise, advice and guidance on feasibility, suitability and logistics of the procedure.

Which national priorities does this work address?

  • Providing high-quality care
  • Reducing secondary care bed occupancy
  • Enhancing quality of life for people with long-term conditions
  • Support people living with frailty to maintain their own health
  • Reducing acute admissions
  • Reducing antimicrobial prescribing
  • Reducing antimicrobial resistance

Results

In 2015, the FMT bank was set up with the equipment installed at PHT. Six donors have been enrolled and screened and the FMT bank has been populated with over 55 aliquots. Standard protocols for laboratory and clinical procedures including quality and training have been developed. Together with a group of past patients and carers, information has been developed about FMT to give patients and carers prior to consent.

37 FMT procedures have now been performed, 19 at Portsmouth and 18 in other hospitals (supplied from the Wessex Faecal Microbiota Bank). An 80% cure rate after one FMT is being achieved locally – the same cure rate seen in scientific studies. So far, no local patients have failed FMT after 2 treatments (100% success locally!).

Given the mortality rates of alternative treatment options and the number of procedures in year one, the service and treatment can be expected to have saved 11 lives so far. Patient feedback has been positive, with an average quality of life increasing by 20 points (out of 100).

There has been high engagement with the Wessex Frozen FMT service from other trusts, and FMT has been performed using the Wessex Faecal Microbiota Bank at hospitals in Dorchester, Bournemouth, Southampton, Chichester, Hampshire, Isle of White, Devon and Exeter, and even as far afield as Jersey. Hospitals in London and Poole have also expressed an interest in the service. There have been several GP referrals to have FMT performed in Portsmouth, and the local CCGs are about to implement an FMT referral pathway. Based on the success of the pilot scheme Portsmouth Hospitals NHS Trust has now implemented FMTs as part of the routine service provided by the Microbiology Department.

“FMT is a uniquely-effective therapy for CDI, and one which comes at relatively low cost. Evidence and ongoing practice demonstrate safety and high success rates.  These translate to dramatic improvements in quality of life for those cured of the heavy burden of Clostridium difficile disease, and generate significant cost savings.”

Dr. Andrew Flatt, MB BChir MSc MA FRCPath, Clinical Lead for Faecal Microbiota Transplantation and Consultant Microbiologist, Queen Alexandra Hospital Portsmouth

Tips for implementation

The fully-functional FMT can serve regional and national NHS providers with expertise, supply of frozen aliquots and tools for research. The FMT bank has the potential to save lives, avoid bed bed-days and save costs to the NHS.

Local implementation is simple, and usually facilitated by a consultant microbiologist or gastroenterologist in their hospital. FMT aliquots can be delivered overnight by established inter-hospital services, ready for use the next day. If you have a patient who may benefit from the service, you can discuss with local specialists and the Wessex Frozen FMT Bank.

Next steps and spread

Wessex AHSN has started joint work with the South West AHSN and Exeter Hospital to create a collaborative infrastructure, develop data, expertise and research, including commercially led projects. There is also currently an ongoing agreement to supply several samples to a research project using FMT in different disease patterns in Wales.

Within the primary site at PHT, an ongoing service evaluation will describe patient quality of life, clinician and patient experience of the service, in addition to key clinical outcomes, and initial data is expected in late 2016. Working with the AHSN, a mathematical model is being developed to determine the potential impact of FMT on the health economy.

The next steps for the service are to raise awareness. To date public awareness has been raised via BBC South Today, Radio Solent, The Daily Mail and The Times newspapers, PHT and Portsmouth University communication channels.

In addition to patient and public awareness, clinical awareness has been essential for service uptake. The channels used to raise clinical awareness include the AHSN, the British Infection Association, the Gut Microbiota for Health group, and local networks and meetings including Research and Innovation and Healthcare Sciences Conferences.

We also plan to raise awareness through local users, publications, and presentations at national Infection and Gastrointestinal conferences. The first year’s data has been accepted for presentation at the Federation of Infection Society’s (FIS) annual conference 2016.

It is our aim to acquire full Medicines and Healthcare Regulatory Agency (MHRA) licensing for our FMT aliquot production – and this would be a first for a UK centre.  With this, we could produce FMT aliquots for use in future research, including clinical trials.

There is a massive potential for research into FMT.  Firstly, analysis of FMT composition and comparison to recipient’s microbiota before and after therapy could enable production of synthetic aliquots for use in CDI.

FMT may also have other therapeutic niches – two areas of particular interest are inflammatory bowel disease and carriage of multi-resistant organisms.

Find out more

Faecal Microbiota Transplant for Recurrent Clostridium difficile Infection; National Institute for Health and Care Excellence 2014
Faecal Microbiota Transplantation for Clostridium difficile infection in the United Kingdom; Porter RJ, Fogg C; Clin Microbiol Infect 2015 Jun; 21(6):578-82
Duodenal infusion of donor feces for recurrent Clostridium difficile; Van Nood E, et al. N Engl J Med. 2013 Jan 31;368(5):407-15.
Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients with Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.
Lee CH et al.  JAMA. 2016 Jan 12;315(2):142-9.
A Review of Management of Clostridium difficile Infection: Primary and Recurrence; Vincent Y, Manji A, Gregory-Miller K and Lee C; Antibiotics 2015, 4, 411-423, doi:10.3390/antibiotics4040411.

Visit the Wessex AHSN website.

Contact for help and advice

Dr Andrew Flatt
andrew.flatt@porthosp.nhs.uk 

Media / communications enquiries:

Michael Goodeve, Head of Communications
michael.goodeve@wessexashn.net

Programme duration: July 2015 – present