Faecal transplants
BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h5149 (Published 20 October 2015) Cite this as: BMJ 2015;351:h5149All rapid responses
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We thank Professors Spector and Knight for highlighting the potential role of faecal microbiota transplantation (FMT) in the management of Clostridium difficile infection (CDI) 1. We also agree with their assertion that long term follow up data are required, given the uncertainties that exist surrounding possible long term adverse consequences of FMT.
However, we feel it necessary to clarify and expand on some of the statements regarding CDI made in the article. Firstly, they quote a recurrence rate of about 25% following initial mild infection. It should be noted that recurrence occurs after all severity grades of CDI and is in fact more common after severe infection 2.
Secondly, the authors state that the standard of care for the treatment of CDI is metronidazole or vancomycin, with or without bowel lavage or probiotics. This statement omits fidaxomicin, a novel antibiotic that was licensed in the UK in 2013. Clinical trials demonstrated that fidaxomicin was non-inferior to vancomycin, and notably that the former was more effective at preventing recurrent infection3,4. Whilst colonic lavage was used in the first randomised controlled trial of FMT 5, in recent UK and European CDI guidelines its role is limited to one component of a possible surgical option for complicated disease (e.g. toxic megacolon or perforation) 6,7. Multiple guidelines advise that there is insufficient evidence to support the use of probiotics in the management of CDI 6-8.
Finally, whilst Spector and Knight state that FMT is being used ‘in people with the whole spectrum of C. difficile infection’, the authors of the systematic review they quote identified only seven patients who had received FMT as initial therapy 9. The vast majority of cases were performed in patients with multiple recurrences of CDI, and it is only for that indication that the procedure is endorsed by the UK National Institute for Health and Care Excellence and the European Society of Microbiology and Infectious Diseases 7,10.
Yours sincerely,
References:
1. Spector T, Knight R. Brit Med J. 2015;351:h5149.
2. Johnson S, Louie TJ, Gerding DN et al. Vancomycin, metronidazole or tolevamer for Clostridium difficile infection: results from two multinational, randomised, controlled trials. Clin Infect Dis. 2014;59:345-54.
3. Louie TJ, Miller MA, Mullane KM et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-31.
4. Cornely OA, Crook DW, Esposito R et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12:281-9.
5. van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368:407-15.
6. Public Health England. Updated guidance on the management and treatment of Clostridium difficile infection. [Online]. London: Public Health England, May 2013. Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/fil...
7. Debast SB, Bauer MP, Kuiper EJ, on behalf of the European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20(Suppl. 2):1-26.
8. 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 for America (SHEA) and the Infectious Diseases. Infect Control Hosp Epidemiol. 2010;31:431-55.
9. Drekonja D, Reich J, Gezahegn S et al. Fecal microbiota transplantation for Clostridium difficile infection. A systematic review. 2015;162:630-8.
10. National Institute of Health and Care Excellence (2014). Faecal microbiota transplant for recurrent Clostridium difficile infection. Interventional procedure guideline 485. London: NICE.
Competing interests: Damian Mawer has received consulting fees and grant support from Astellas. Mark Wilcox has received: consulting fees from Actelion, Astellas, MedImmune, Merck, Pfizer, Sanofi-Pasteur, Seres, Summit, and Synthetic Biologics; lecture fees from Alere, Astellas, Merck & Pfizer; and grant support from Actelion, Astellas, bioMerieux, Da Volterra, Merck and Summit.
Dear Editor
We welcome the Editorial from Profs Spector and Knight summarising the current clinical role and potential future directions of faecal microbiota transplantation (FMT) in the UK and beyond (1). Having recently established an FMT programme ourselves, we felt there were two further relevant points worth emphasising.
Firstly, a point regarding clinical aspects. Whilst at present the UK has a relatively permissive regulatory framework regarding administration of FMT as the authors describe, we encountered considerable practical obstacles in attempting to establish an NHS programme. Screening of donors is expensive (>£500 per screen per donor, repeated at least six monthly), with it being unclear as to who is best placed to fund this. Trust committees are unsure as to whether governance of an FMT programme falls under the remit of microbiology, gastroenterology, pharmacy or elsewhere. There is reluctance in transferring potentially suitable recipients with recurrent C. difficile infection at other hospitals into the FMT centre (because of concerns regarding infection prevention and control implications); conversely, clinicians from the FMT centre cannot take transplant material to other hospitals until the lengthy process of issuing an honorary contract can be arranged, by which time the patient may have deteriorated to a state beyond feasibility of treatment. Similar concerns have been noted by others as well (2), and may introduce the true risk of FMT not being provided within the UK to patients who stand to benefit substantially. A practical solution would be the establishment of regional FMT networks, with a ‘hub’ centre (that co-ordinated the donor pool and prepared transplant material) and ‘spoke’ centres (with agreed local protocols with the hub centre regarding identification of potential recipients and logistics of transfer for FMT delivery), with recipient follow-up shared between all centres in the network.
Secondly, a point regarding research aspects. Whilst there is certainly great interest in the potential therapeutic implications that FMT may hold for a wide range of conditions, it is important to state that the exact mechanisms by which FMT works to treat C. difficile infection remains largely unclear. Unravelling the means by which FMT influences the interaction between the gut microbiota and the host metabolism and immune system is clearly of paramount importance (3). There is no currently established means by which a donor for FMT is matched to a particular recipient; given that FMT works so effectively as treatment for C. difficile infection in the majority of cases, it may in fact be that analysis of the few donors from whom donated stool does not enact remission of C. difficile infection are of greatest significance in achieving this goal. As such, researchers having access to donors for sample collection and analysis and maintenance of robust clinical records of outcomes from FMT for each donor is essential. Whilst we agree with Spector and Knight that not-for-profit companies running ‘stool banks’ may have a valuable role to play in increasing access to FMT (1), it is not clear at present whether they are prepared to undertake this interaction with clinicians and academia that is so key to making scientific advancement within this field.
1. Spector T, Knight R. Faecal transplants. BMJ (2015);351:h1549.
2. Porter RJ, Fogg C. Faecal microbiota transplantation for Clostridium difficile infection in the United Kingdom. Clin Microbiol Infect (2015);21(6):578-582.
3. Holmes E, Li JV, Marchesi JR, Nicholson JK. Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. Cell Metab (2012);16(5):559-564.
Competing interests: No competing interests
Re: Faecal transplants
We thank Mawer and Wilcox for pointing out that there are newer antibiotics that are possibly superior to Vancomycin for treatment of recurrent C.Diff . However, the gulf in efficacy between these treatments and FMT is so large that transplant will remain the treatment of choice, especially since FMT is much cheaper, and doesn't risk further antibiotic related problems and drug resistance.
We thank Mullish & Williams for pointing out the considerable practical challenges facing clinicians in the UK. We agree rules need to be relaxed or changed such as allowing easy access to donors or well regulated stool banks in other centres or countries. We also agree that investment is needed in screening donor samples to improve compatibility.
Competing interests: No competing interests