Interventional procedure consultation document

Faecal microbiota transplant for recurrent Clostridium difficile infection

Infections caused by bacteria called Clostridium difficile (C. difficile) in the gut can cause severe diarrhoea and illness. It usually occurs after antibiotic therapy, which can upset the balance of bacteria in the gut. Faecal microbiota transplant involves putting faeces from a healthy donor into the gut of the affected person, to restore a normal balance of bacteria.

The National Institute for Health and Care Excellence (NICE) is examining faecal microbiota transplant for recurrent C. difficile infection and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of specialist advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about faecal microbiota transplant for recurrent C. difficile infection.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

• comments on the provisional recommendations
• the identification of factual inaccuracies
• additional relevant evidence, with bibliographic references where possible.

Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

• The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the NICE website.

Through its guidance NICE is committed to promoting race and disability equality, equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our interventional procedures guidance. In particular, we aim to encourage people and organisations from groups who might not normally comment on our guidance to do so.

In order to help us promote equality through our guidance, we should be grateful if you would consider the following question:

Are there any issues that require special attention in light of NICE’s duties to have due regard to the need to eliminate unlawful discrimination, advance equality of opportunity, and foster good relations between people with a characteristic protected by the equalities legislation and others?

Please note that NICE reserves the right to summarise and edit comments received during consultations or not to publish them at all where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.

 

Closing date for comments: 21st November 2013

Target date for publication of guidance: 26 February 2014

 

 

 

1        Provisional recommendations

1.1   Current evidence on the efficacy and safety of faecal microbiota transplant for recurrent Clostridium difficile infection is adequate to support the use of this procedure provided that normal arrangements are in place for clinical governance, consent and audit.

1.2    This procedure should only be considered for patients with recurrent C. difficile infections who have had at least 2 courses of antibiotic treatment.

1.3    NICE encourages further research into faecal microbiota transplant for C. difficile infection, specifically to investigate optimal dosage, mode of administration and choice of donor.

 

 

 

2    Indications and current treatments

2.1  Clostridium difficile is a bacterium that lives harmlessly in the gut of approximately 5% of healthy individuals. The use of broad-spectrum antibiotics and immunosuppressive agents can alter the balance of bacterial species in the gut, resulting in an overgrowth of C. difficile. Symptoms of mild C. difficile infections include purulent watery diarrhoea, abdominal cramps, nausea and dehydration. In more severe cases the infection can cause bloody diarrhoea, a distended colon and fever. In a few people C. difficile infection can lead to pseudomembranous colitis, leucocytosis, sepsis, toxic megacolon, colonic rupture, and death.

2.2   First-line treatment involves rehydration and a 10–14 day course of orally administered antibiotics such as vancomycin or metronidazole. Clinical responses are generally favourable; however, some people suffer from recurrent or refractory C. difficile infections. For these people, repeat treatment with vancomycin or metronidazole, or other antibiotics such as fidaxomicin are used.

 

 

 

 

3   The procedure

3.1  Faecal microbiota transplants aim to restore a healthy balance of bacteria in the gut of people who have recurrent Clostridium difficile infections by introducing enteric bacteria from the faeces of healthy donors.

3.2  Before the procedure, donors, who are usually family members, are screened for viruses and parasites. Donor faeces are taken and diluted with water, saline or another solution such as milk or yogurt, and subsequently strained to remove large particles. The resulting suspension is introduced into the recipient’s gut via a nasogastric tube, nasoduodenal tube, rectal enema or via the biopsy channel of a colonoscope. Recipients may receive a bowel lavage before transplantation, in order to reduce the C. difficile load in the intestines.

 

 

 

4   Efficacy

This section describes efficacy outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview.

4.1    A randomised controlled trial of 43 patients treated by faecal transplant versus vancomycin with a bowel lavage versus vancomycin only, reported symptom resolution with laboratory confirmation of negative stool samples in 94% (15/16), 23% (3/13) and 31% (4/13) of patients, respectively at 10-week follow-up. The faecal transplant group exhibited significantly higher cure rates compared to the vancomycin with bowel lavage and vancomycin-only groups (p<0.001).

4.2   A systematic review of 25 studies, which included 289 patients with refractory Clostridium difficile infection treated by a faecal transplant, reported complete resolution of symptoms in 91% of patients at a mean follow-up of 12.6 months.

4.3   A non-randomised comparative study of 43 patients treated by faecal transplants using fresh stool from a related donor, transplants using fresh stool from an unrelated donor or transplants using frozen stool from an unrelated donor, reported resolution of symptoms with negative stool samples in 70% (7/10), 92% (11/12) and 90% (19/21) of patients respectively at 12-month follow-up. There were no statistically significant differences between the success rates of related and unrelated donor faeces or between the success rates of fresh and frozen faeces.

4.4    The randomised controlled trial of 43 patients treated by a faecal transplant, vancomycin with bowel lavage, or vancomycin only, reported relapses within 5 weeks of the start of therapy in 6% (1/16), 54% (7/13) and 62% (8/13) of patients respectively. 

4.5   The systematic review of 25 studies reported that 2.4% (7/289) of patients had a relapse between 29 days and 4 years after faecal microbiota transplantation.

4.6    The specialist advisers listed key efficacy outcomes as cure of infection and no further relapses of C. difficile infection.

 

 

 

5     Safety

This section describes safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview.

5.1   Belching, abdominal cramps and abdominal pain, on the day of faecal transplant, were reported in 19% (3/16), 31% (5/16) and 13% (2/16) of patients respectively in a randomised controlled trial of 43 patients treated by faecal transplant, vancomycin with a bowel lavage or vancomycin only. In the same study, diarrhoea that was not considered to be due to Clostridium difficile infection was reported in 94% (15/16) of patients on the day of faecal transplant. Constipation (during the 10-week follow-up period) was reported in 19% (3/16) of patients.

5.2   Suspected peritonitis was reported in 1 patient (timing not reported), and 3 patients had symptoms of enteritis within 2 days of receiving a faecal transplant, in the systematic review of 25 studies.

5.3   The specialist advisers stated that theoretical adverse events include the transmission of biological agents and infections, and the administration of microbiologically uncharacterised material.

 

 

 

6    Committee comments

6.1  The Committee noted that religious beliefs, especially those related to diet, may influence the decision to donate or receive a faecal transplant.

6.2   The Committee recognised that the enteric infusion of donor faeces is not a transplant in the usual sense of transplanting body tissues, but it accepted that faecal microbiota transplant has become an accepted term to describe this procedure. 

 

 

 

7     Further information

7.1   For related NICE guidance see the NICE website.

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

October, 2013

 

_{Personal data will not be posted on the NICE website. In accordance with the Data Protection Act names will be anonymised, other than in circumstances where explicit permission has been given.}

 _{It is the responsibility of consultees to accurately cite academic work in order that they can be validated.}