The recent FDA warning due to the death of a patient following an investigational fecal microbiota transplant (FMT) brought to light many questions and concerns. The biggest question being, “In what situation did these deaths occur?” The report indicates that two immunocompromised patients received FMT and developed a multi-drug resistant infection and one of them died. We do not know if this FMT was done to help treat Clostridioides difficile (C. diff) infection, or for a different indication.
Large, phase 3 clinical trials for C. diff are currently excluding immunocompromised patients. This unfortunate outcome and the FDA safety alert that followed, has led physicians and researchers to think about how this adverse event could be prevented in the future.
We are grateful to the FDA for bringing this situation to light. We are receiving guidance from the FDA regarding additional testing for donors, including testing frequency, stool storage, information to include in donor questionnaires, etc., to ensure the safety of patients. Certain extended spectrum beta-lactamases (ESBL) and other multi-drug resistant organisms (MDRO) bacteria are difficult to test for in stool and there is a need to develop improved tests.
These efforts would lead to improved standardization of donor screening. The Annals of Internal Medicine published an article that revealed a wide variability in FMT reporting, highlighting that several characteristics of stool transplantation were not reported well.
We should ensure that patients are aware of known and unknown risk factors associated with FMT. As a physician, I discuss with all my patients eligible for this procedure that although FMT has been around for some time, it is still considered investigational and not FDA approved. It is experimental, and we do not know the long-term and short-term benefits. We’re hopeful to get more information on these patient cases in due course of time.
We still need more data regarding the potential for serious adverse events, such as the recent safety issue highlighted by the FDA. The AGA has established a registry that aims to look at the 10-year safety of FMT. We and many other centers in the country are participating in the registry.
FMT has been deemed successful to treat multiply recurrent C. diff infection when antibiotics and other measures fail to lead to sustained improvement. There is ongoing research to move to defined microbial consortia to treat C. diff as we further understand the mechanisms of FMT.
Sahil Khanna, MBBS
Disclosures: Khanna reports receiving research funding from Rebiotix, Inc., a Ferring company.