[Updated Post 06/18/2019]
AUDIENCE: Patient, Healthcare Professional
ISSUE: The FDA is now aware of bacterial infections caused by multi-drug resistant organisms (MDROs) that have occurred due to transmission of a MDRO from use of investigational fecal microbiota for transplantation (FMT):
- 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 these serious adverse reactions occurred with investigational FMT, FDA has determined that additional protections are needed for any investigational use of FMT. FDA has notified all Investigational New Drug (IND) holders of these requirements and that they need to implement these new requirements no later than July 15, 2019.
RECOMMENDATION: Patients considering FMT to treat C. difficile infection should speak to their health care provider to understand the potential risks associated with the product’s use.
To ensure that all stakeholders are fully informed, FDA is providing the following information that has been communicated to IND holders:
- Donor screening must include questions that specifically address risk factors for colonization with MDROs, and individuals at higher risk of colonization with MDROs must be excluded from donation. Examples of persons at higher risk for colonization with MDROs include:
- Health care workers
- Persons who have recently been hospitalized or discharged from long term care facilities
- Persons who regularly attend outpatient medical or surgical clinics
- Persons who have recently engaged in medical tourism
- FMT donor stool testing must include MDRO testing to exclude use of stool that tests positive for MDRO. The MDRO tests should at minimum include extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Culture of nasal or peri-rectal swabs is an acceptable alternative to stool testing for MRSA only. Bookend testing (no more than 60 days apart) before and after multiple stool donations is acceptable if stool samples are quarantined until the post-donation MDRO tests are confirmed negative.
- All FMT products currently in storage for which the donor has not undergone screening and stool testing for MDROs as described above must be placed in quarantine until such time as the donor is confirmed to be not at increased risk of MDRO carriage and the FMT products have been tested and found negative. In the case of FMT products manufactured using pooled donations from a single donor, stored samples of the individual donations prior to pooling must be tested before the FMT products can be administered to subjects.
- The informed consent process for subjects being treated with FMT product under your IND going forward should describe the risks of MDRO transmission and invasive infection as well as the measures implemented for donor screening and stool testing.
FDA may consider alternative proposals that achieve equivalent risk mitigation as the measures outlined above.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
- Complete and submit the report Online
- Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
[06/18/2019 - Safety Communication - FDA]
[06/14/2019 - Safety Communication - FDA]