Friday, June 14, 2019

FDA Warns On Infection Risks Of Fecal Transplants

C. difficile – Credit CDC PHIL


Nearly 50 years ago Dr. William Nolan wrote a book called `The Making of A Surgeon’, about his internship at Bellevue Hospital in the 1950s that, quite frankly, inspired me to become an EMT, and then a Paramedic.  While dated, it still a good read, and highly recommended.
I mention it because one of the anecdotes he relates was a hysterically funny account about how he, and two other interns, concocting a `feces laced milkshake’  to try to cure a patient with intractable diarrhea, likely due to a C. Diff infection. 
Over the last decade, the idea of using `fecal transplants' has gotten a good deal of press, and early results have been very promising (see 2013's NEJM: Effectiveness Of Fecal Transplants For C. diff).
Clostridium difficile – or C. diff – is a bacterial intestinal infection which claims tens of thousands of lives each year, and is – as the name implies – very difficult to treat.
Usually brought on by the use of antibiotics  - which kill off good gut bacteria along with the bad guys – C. diff can produce prolonged, and often life threatening bouts of diarrhea.
The idea behind a `fecal transplant’ is the re-introduction of good bacteria to afflicted patient’s gut biome. 
Yesterday, the FDA issued an alert following two adverse reactions (1 fatal) in immunocompromised recipients from invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli).

The Food and Drug Administration (FDA) is informing health care providers and patients of the potential risk of serious or life-threatening infections with the use of fecal microbiota for transplantation (FMT).  The agency 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 FMT.

Summary of the Issue
  • 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.
Information for Health Care Providers and Patients

In July 2013, FDA issued guidance stating that it intends to exercise enforcement discretion under limited conditions regarding the IND requirements for the use of FMT to treat Clostridium difficile (C. difficile) infection in patients who have not responded to standard therapies. The guidance states that FDA intends to exercise enforcement discretion provided that the treating physician obtains adequate consent for the use of FMT from the patient or his or her legally authorized representative. The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks. FDA is informing members of the medical and scientific communities and other interested persons of the potential risk of transmission of MDROs by FMT and the resultant serious adverse reactions that may occur.

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.

Additional Protections for Investigational Use of FMT
  • Because of these serious adverse reactions that occurred with investigational FMT, FDA has determined that the following 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.
Reporting Adverse Events
FDA encourages all health care providers administering FMT products to report suspected adverse events to the FDA at 1-800-FDA-1088 or
While clinical trials have been temporarily halted so they can implement new safety and testing protocols, and the procedure is not yet FDA approved, a large number of `experimental' fecal transplants occur every year. 
While many are done by legitimate doctors, home D-I-Y transplants have become a `wellness' trend on YouTube, Facebook, and other social media outlets, and `how-to' videos and instructions abound (see WebMD The Rise of the Do-It-Yourself Fecal Transplant).
Hopefully the FDA's warnings will get as much play on social media as the `how-to' videos have.