The aim of microbiome restoration is to repopulate a diverse gut microbiota to treat disease. For recurrent C. diff infection, one historic approach has been fecal microbiota transplant (FMT).
Data suggest FMT is efficacious for the treatment of recurrent CDI and reestablishes biodiversity in the gut.1
However, several limitations are found across clinical studies, diagnosis, and treatment.1
There is variability across clinical trials—cure rates were lower in randomized controlled trials than in open-label studies (67.7% vs 82.7%, respectively; P<.001)2,3
This inconsistency is due to considerable heterogeneity among randomized controlled trials, with marked differences in study structure, control groups, fecal transplant materials, and outcome assessments.4
Also, most studies assessing the benefits of FMT are retrospective case series or systematic reviews of contrasting sources of microbiota and limited safety data.5-7
Likewise, the lack of product standardization and administration methods has created a situation where a regulated, safe, and effective product is critically needed.8
- In fact, as recently as March 2020, the FDA issued a warning of the potential risk of serious or life-threatening infections following investigational use of an FMT product supplied by a US stool bank company9
Patients ENROLLED IN CLINICAL TRIALS may not be a true reflection of patients seen in the real world
- Strict inclusion and exclusion criteria in randomized controlled trials lead to inclusion of a small portion of patients from daily clinical practice, limiting generalizability of results to patients seen in clinical practice3
CDI testing is inconsistent in clinical practice
There is no gold standard: sensitivity and specificity of current toxin tests for CDI are highly variable. Moreover, in the US, there is no consensus on best diagnostic testing for CDI.10
- C. diff colonization is common and can complicate diagnosis since its toxins can be detected but aren't necessarily causing disease11
- Patients can suffer and resolve an active infection, but harbor spores, putting them at risk for another potentially deadly infection11
- Colonization does not require treatment12
- van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-415.
- Tariq R, Pardi DS, Bartlett MG, Khanna S. Low cure rates in controlled trials of fecal microbiotatransplantation for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Clin Infect Dis. 2019;68(8):1351-1358.
- Bafeta A, Yavchitz A, Riveros C, Batista R, Ravaud P. Methods and reporting studies assessing fecal microbiota transplantation: a systematic review. Ann Intern Med. 2017;167(1):34-39.
- Feuerstadt P, Aroniadis OC, Svedlund FL, Strong L, Boules M, Khanna S. Heterogeneity of randomized controlled trials of fecal microbiota transplantation (FMT) in recurrent Clostridioides difficile infection: a systematic review. AGA Abstracts. 2020;158(6 suppl 1):s-900.
- Drekonja D, Reich J, Gezahegn S, et al. Fecal microbiota transplantation for Clostridium difficile infection: a systematic review. Ann Intern Med. 2015;162(9):630-638.
- Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108(4):500-508.
- Rossen NG, MacDonald JK, de Vries EM, et al. Fecal microbiota transplantation as novel therapy in gastroenterology: a systematic review. World J Gastroenterol. 2015;21(17):5359-5371.
- Joseph J, Saha S, Greenberg-Worisek AJ. Fecal microbiota transplantation: an ambiguous translational pathway for a promising treatment. Clin Transl Sci. 2019;12(3):206-208.
- US Food & Drug Administration website. Fecal Microbiota for Transplantation: Safety Alert – Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms. https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota-transplantation-safety-alert-risk-serious-adverse-events-likely-due-transmission. Accessed April 26, 2021.
- Guh AY, Mu LG, Winston LG, et al. Trends in U.S. burden of Clostridioides difficile infection and outcomes. N Engl J Med. 2020;382(14):1320-1330.
- Crobach MJT, Vernon JJ, Loo VG, et al. Understanding Clostridium difficile colonization. Clin Microbiol Rev. 2018;31(2):1-29.
- Schäffler H, Breitrück A. Clostridium difficile—from colonization to infection. Front Microbial. 2018;9(646):1-12.