The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis

Abstract

The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.

Gastrointestinal symptoms associated with COVID-19: impact on the gut microbiome

“…Donors for fecal microbiota transplant for SARS-CoV-2 must be strict and validated to prevent the potential risk of transmission. 39 The results show that the elevated levels of fecal calprotectin in patients with COVID-19 add to the growing evidence that SARS-CoV-2 infection causes an inflammatory response in the intestine. 40 Calprotectin concentrations were significantly higher in COVID-19 patients who had suffered from diarrhea and with more elevated serum IL-6 levels.…”

Faecal microbiota transplantation for recurrent Clostridioides difficile infection: An updated systematic review and meta-analysis

“…Still, no clear clinical evidence exists for the cumulative effect of FMT following single or repeated treatment regimens, and the quality of evidence for FMT compared with standard antibiotics has been rated as moderate in previous systematic reviews and guidelines due to inconsistencies [ 10 , 13 ]. These inconsistencies have resulted in caution and questioned the position of FMT in the CDI treatment algorithm until the evidence for FMT has been evaluated in more detail [18] . Now, further to these earlier systematic reviews, more evidence has accumulated, and new methods of delivery have emerged; as such, an update of the evidence with the latest data is pivotal to guide clinical decisions and improve the future recommendations for FMT in managing patients with recurrent CDI.…”

Should We Be Worried About Clostridioides difficile During the SARS-CoV2 Pandemic?

“…Another problem that COVID-19 may cause relates to fecal microbiota transplantation (FMT) (Chiu et al, 2020 ; Khanna and Pardi, 2020 ), which is used for recurrent cases of CDI, accounting for 40–60% of cases (Martin and Wilcox, 2016 ), in particular, for those patients whose treatment failed, which represent 5–10% of cases (Vigvari et al, 2015 ). FMT is based on stools donated by volunteers, which are screened and so are considered healthy donors Although FMT seems to reduce the risk for recurrent CDI, the efficacy and safety of this procedure is still under evaluation, especially because the inconsistency found with clinical trials (Wilcox et al, 2020 ) and deficiency of standards methods for producing FMT (Nicco et al, 2020 ). In addition to the possible transmission of opportunistic and AMR bacteria, in light of the SARS-CoV-2, all microbiome replacement therapies from now on will require accurate diagnosis to guarantee their safety or, may need to be suspended until the pandemic is over.…”