Fecal Microbiota Transplantation (FMT) & Clostridioides difficile infection (CDI) (recurrent)

In the context of Fecal Microbiota Transplantation (FMT) & Clostridioides difficile infection (CDI) (recurrent), the European Consensus guidelines (1) recommend Fecal Microbiota Transplantation (FMT) for mild and severe recurrent Clostridioides difficile infection (CDI) and suggest consideration for CDI refractory to the initial antibiotic treatment (2). According to US Guidelines published in 2018, Fecal Microbiota Transplantation (FMT) is proposed in patients with at least two recurrences (11).

Because fecal microbiota transplantation (FMT) was significantly more effective than the use of vancomycin in curing recurrent C. difficile infection, it is used and approved to treat severe recurrent Clostridioides difficile infection (CDI) (18, 19, 20, 21). Fecal Microbiota Transplantation (FMT) can cure recurrent Clostridioides difficile infection (CDI) in up to 95% of patients (23).

Fecal Microbiota Transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection (CDI). FMT's success in CDI has sparked interest. The mechanisms behind FMT's efficacy are not fully known. A deeper understanding may reveal FMT's full potential and improve its clinical efficacy, safety, and usability. It could be a tool for other diseases (7). At present, Fecal Microbiota Transplantation (FMT) is only recommended in the treatment of recurrent Clostridioides difficile infection (CDI) (8, 22).

Fecal Microbiota Transplantation (FMT) is also recommended as a potential treatment for recurrent Clostridioides difficile infection (CDI) in children (9). Nine of the 10 (90%) children had resolution of their Clostridioides difficile infection (CDI) symptoms after a single-infusion Fecal Microbiota Transplantation (FMT) with follow-up of 1 month to 4 years (19).

Mode of action

Khoruts and Sadowsky have reviewed mechanisms underlying Fecal Microbiota Transplantation (FMT) efficacy. They include restoration of the colonic microbial community and inhibition of C. difficile by competition for nutrients, direct suppression by antimicrobial peptides, bile-acid-mediated inhibition of spore germination and vegetative growth, and activation of immune-mediated colonization resistance (15)

In Clostridioides difficile infection (CDI) , where the intestinal niche is severely affected by Clostridioides (Clostridium) difficile domination, an overgrowth of Candida species has been associated with a negative outcome of Fecal Microbiota Transplantation (FMT), a finding that has been replicated in mouse models (12, 13, 14). Fecal Microbiota Transplantation (FMT) is a highly effective treatment for overgrowth of Clostridium difficile (17).

Clinical data

Fecal microbiota transplantation (FMT) is probably best known for its outstanding efficacy in recurrent or refractory Clostridioides difficile infection (CDI), with more than 90% cure rate (16).

According to several recently published systematic reviews and meta-analyses (3, 4, 5), Fecal Microbiota Transplantation (FMT) has been successfully used in treating recurrent Clostridioides difficile infection (CDI) (recurrent) with a cure rate of roughly 90% (2).

A meta-analysis to review the use of Fecal Microbiota Transplantation (FMT) for prevention of recurrent CDI identified 11 studies with 273 patients through 2012. the overall resulting efficacy was about 90% and no substantial FMT-related adverse events were reported (4).

Another systematic review with meta-analysis has included 37 studies: seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.070.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent, but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon. Conclusion: Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery (5)

A meta-analysis was conducted to examine the effectiveness of fecal microbiota transplant (FMT) in preventing recurrent Clostridioides difficile infection (CDI). This analysis included 11 studies, encompassing a total of 273 patients, up until the year 2012. The findings indicated an overall efficacy rate of approximately 90%, and importantly, no significant adverse events related to FMT were reported (6).

Several systematic reviews and meta-analyses also have reported Fecal Microbiota Transplantation (FMT) to have an overall efficacy rate between 80% and 90% in successfully treating and preventing further recurrent Clostridioides difficile infection (CDI) in following a single Fecal Microbiota Transplantation (FMT) (5, 10).

Protocols for treating recurrent Clostridioides difficile infection (CDI) through Fecal Microbiota Transplantation (FMT) are still not standardised. Fifteen studies (1150 subjects) were analysed. Multiple infusions increased efficacy rates overall (76% versus 93%) and in each route of delivery (duodenal delivery: 73% with single infusion versus 81% with multiple infusions; capsule: 80% versus 92%; colonoscopy: 78% versus 98% and enema: 56% versus 92%). Duodenal delivery and colonoscopy were associated, respectively, with lower efficacy rates (p = 0.039) and higher efficacy rates (p = 0.006) overall. Fecal amount  50g (p = 0.006) and enema (p = 0.019) were associated with lower efficacy rates after a single infusion. The use of fresh or frozen feces did not influence outcomes. Routes, number of infusions and fecal dosage may influence efficacy rates of Fecal Microbiota Transplantation (FMT) for rCDI. These findings could help to optimise FMT protocols in clinical practice (10).

References:

(1) Cammarota et al. 2017 Gut 66: 569–80
(2) Ortigão et al. 2020
(3) Brandt et al. 2012 Am J Gastroenterol. 107(7): 1079-87
(4) Kassam et al. 2013 In: Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK133560/
(5) Quraishi et al. 2017 Aliment Pharmacol Ther 46: 479-93
(6) Kassam et al. 2013 The American journal of Gastroenterology 108(4): 500-8
(7) Segal et al. 2020
(8) Allegretti et al. 2019 Lancet 394: 420-31
(9) Davidovics et al. 2019 JPGN 68: 130–43
(10) Ianiro et al. 2018 United European Gastroenterol J 6: 1232-44
(11) McDonald et al. 2018 Clin Infect Dis 66: 987–94
(12) Zuo et al. 2018 Nat. Commun. 9: 3663
(13) Li et al. 2019u Immunity 50: 1365-1379
(14) Panpetch et al. 2019 PLoS ONE 14: e0210798
(15) Khoruts & Sadowsky 2016 Nat Rev Gastroenterol Hepatol 13(9): 508-16
(16) Walker et al. 2016 Lancet Oncol. 17: 164-173
(17) Ericsson & Franklin 2015 ILAR Journal 56(2): 205-217
(18) van Nood et al. 2013 N Engl J Med 368: 407-15
(19) Russell et al. 2014
(20) Jung Lee et al. 2015 Gastroenterol. Hepatol. (N. Y.) 11: 24–32
(21) Vyas et al. 2015 World J. Gastroenterol. 21: 6–11
(22) Weingarden et al. 2015 Microbiome 3: 10
(23) Britton & Young 2014

see also:
Adverse Events / Safety & Fecal Microbiota Transplantation (FMT)
Clostridioides difficile infection (CDI)
Clostridioides difficile infection (CDI) & Gut microbiota
Clostridioides difficile infection (CDI) (recurrent) & Drugs/Treatments
CP101 & Clostridioides difficile infection (CDI) (recurrent)
Fecal Microbiota Transplantation (FMT) & Preclinical/Clinical data
Microbial Ecosystem Therapeutics 2 (MET-2) & Clostridioides difficile infection (CDI) (recurrent)