The U.S. Food and Drug Administration (FDA) issued a warning yesterday concerning the potential risks of Fecal Microbiota for Transplantation (FMT) following the death of a patient.
Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the individuals died.
FMT used in these two individuals were prepared from stool obtained from the same donor.
The donor stool and resulting FMT used in these two individuals were not tested for ESBL-producing gram-negative organisms prior to use. After these adverse events occurred, stored preparations of FMT from this stool donor were tested and found to be positive for ESBL-producing E. coli identical to the organisms isolated from the two patients.
Because of these serious adverse reactions, FDA has determined that certain donor screening and stool testing protections are needed for any investigational use of FMT:
- Donor screening with questions that specifically address risk factors for colonization with MDROs, and exclusion of individuals at higher risk of colonization with MDROs.
- MDRO testing of donor stool and exclusion of stool that tests positive for MDRO. FDA scientists have determined the specific MDRO testing and frequency that should be implemented.
“The medical community is actively engaged in exploring the potential uses of Fecal Microbiota for Transplantation, or FMT. Although FMT is not approved by the FDA for any use, the agency plays a critical role in supporting product development while assessing the risks and benefits to patients of unapproved therapies. The agency also works to strike a balance between assuring patient safety and facilitating access to unapproved treatments for unmet medical needs. For example, the FDA has issued guidance stating that it intends to exercise enforcement discretion, under limited conditions, regarding the investigational new drug requirements for FMT used to treat Clostridium difficile infection unresponsive to standard therapies,” said Peter Marks, M.D., Ph.D., director of FDA’s Center for Biologics Evaluation and Research.
“While we support this area of scientific discovery, it’s important to note that FMT does not come without risk. We’ve become aware of infections with multi-drug resistant organisms after patients received investigational FMT, including one patient death. We therefore want to alert all health care professionals who administer FMT about this potential serious risk so they can inform their patients. Today’s safety communication underscores the importance of why new therapies are thoroughly studied to ensure the benefits of taking them outweigh the risks to patients, and we will continue to aggressively monitor clinical trials to ensure patients are protected when safety concerns arise.”