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Using a faecal microbiota transplant cured 92% of people with Clostridium difficile that had recurred or had not responded to antibiotics. Faecal transplant also had a lower risk of treatment failure than the antibiotic vancomycin.
C. difficile is a potentially serious infection of the gut that can occur after a course of antibiotics unbalances the gut bacteria. Faecal transplant uses the diluted faeces of a healthy person delivered into the guts of the person with C. difficile to rebalance their gut bacteria.
Administering the transplant via colonoscopy or enema was more effective than via a stomach tube. This may help patients to overcome the aesthetic qualities of this treatment.
This review revealed many variations in how transplants were prepared and administered, so further work is needed to find the best preparation and volume. Capsules are another option to be considered.
Why was this study needed?
C. difficile is the most important cause of diarrhoea related to antibiotic use, mainly affecting the old and infirm. It can cause serious bowel damage and be life-threatening. UK infection rates have reduced from 55,498 in 2007/8 to 12,840 in 2016/17 due to strict infection control measures and NHS sanctions of £10,000 per case due to a lapse in care.
The infection is usually treated with antibiotics. However, one in three people will get C. difficile again, and recurring infections can be difficult to treat. UK guidelines recommend faecal transplant if antibiotics have failed. This involves preparing the bowel with strong laxatives and then an infusion of diluted faeces.
Only some centres use this treatment. A 2016 survey suggested this is due to a perceived a lack of evidence, no standardised approach and uncertainty about long-term effects. This review aimed to bring together studies to provide a comprehensive view.
What did this study do?
This systematic review and meta-analysis included seven randomised controlled trials of 428 participants and 30 case series of 1,545 participants. Most studies looked at older adults; some included children and younger people with weakened immune systems. There were no UK based studies.
Faecal transplant techniques varied: lower or upper bowel application, fresh or frozen stools, and one or more infusion. Donors were family members and healthy volunteers, screened for viruses and gut problems. Follow up ranged from 10 weeks to eight years. Many studies used reduction in diarrhoea as a marker of effectiveness, rather than C. difficile toxin levels.
The randomised trials were assessed as low risk of bias. Including case series, the range of interventions used and variation across studies all reduce our confidence in the findings.
What did it find?
- Two randomised controlled trials (81 participants) showed 90% response to faecal transplant compared with less than 30% to antibiotics (relative risk of failure [RR] 0.23, 95% confidence interval [CI] 0.20 to 0.80).
- Overall, faecal transplant had a high response rate of 92% (95% CI 89% to 94%) across all studies. Treatment response increased with each dose in cases where it did not work the first time. There was no difference in people’s response to treatment when using fresh (92%) or frozen faecal transplant (93%).
- Administering the faecal transplant via the stomach was less effective (83% response rate) compared to administering it via colonoscopy or enema (90% response rate) across all studies.
- There was one report of bowel micro perforation, and some people had a worsening of their diarrhoea. However, most people just had minor gastric symptoms (diarrhoea, constipation and cramping). Some people who already had inflammatory bowel disease experienced a flare-up following transplantation.
What does current guidance say on this issue?
NICE 2014 guidance recommends faecal transplant in people with recurrent C. difficile that has not responded to antibiotics and other treatments. It recommends that a confidential record of the donor and recipient’s details are kept. NICE judges that current evidence of its efficacy and safety is adequate. However, they encourage further research focusing on aspects of implementation such as dosage, mode of administration and donor screening.
Public Health England 2013 guidelines also recommend faecal transplant as a treatment option for multiple episodes of recurrent C. difficile.
What are the implications?
Although these studies had wide variations in preparation and administration, faecal transplant appeared to be an effective and safe way to treat recurring or unresponsive diarrhoea from C. difficile. Providing this further robust evidence may encourage its use.
This review provides useful information about the best delivery route for the transplant, and that frozen or fresh samples are equally effective. A recent trial shows that taking a capsule may also be an alternative effective and acceptable route for transplant.
However, there remains uncertainty about how best to prepare the faecal transplant, and evidence is needed to guide best practice.
Citation and Funding
Quraishi MN, Widlak M, Bhala N, et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther. 2017;46(5):479-93.
No funding information was provided for this study.
Bibliography
Goldenberg, S. Practical aspects of faecal microbiota therapy (FMT) for recurrent C. difficile Infection (CDI). London: Public Health England; updated 2015.
Kao D, Roach B, Silva M, et al. Effect of oral capsule – vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection. A randomized clinical Trial. JAMA. 2017;318(20):1985–93. doi:10.1001/jama.2017.17077.
NHS Choices. Clostridium difficile. London: Department of Health; updated 2016.
NICE. Faecal microbiota transplant for recurrent Clostridium difficile infection. IPG485. London: National Institute for Health and Care Excellence; 2014.
PHE. Updated guidance on the management and treatment of Clostridium difficile infection. London: Public Health England; updated 2013.
Rao K, Young VB, Malani PN. Capsules for fecal microbiota transplantation in recurrent Clostridium difficile infection. The new way forward or a tough pill to swallow? JAMA. 2017;318(20):1979–1980. doi:10.1001/jama.2017.17969.
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