Doctors from the hospital that treated a patient who died after a fecal microbiota transplant published a case study on Wednesday in the New England Journal of Medicine that offers more details on the case as well as another case in which a patient became severely ill from the procedure.
FDA announced in June that it had become aware that patients who undergo FMT can experience severe or life-threatening bacterial infections caused by drug-resistant bacteria. FDA said two patients with weakened immune systems who received FMT developed infections stemming from extended-spectrum-beta-lactamase (ESBL) producing E. coli, which is resistant to antibiotics. FDA reported that one of those patients had died.
FDA said both FMTs involved stool from the same donor. The donor's stool had not been tested for ESBL-producing gram-negative organisms before the providers conducted the transplants, according to FDA.
FDA said the donor's stool underwent lab tests after the two patients experienced adverse reactions, and the tests confirmed the stored stool contained ESBL-producing E. coli identical to the bacteria found in stool used in the two transplants.
As a result of the developments, FDA issued new safety guidelines for FMTs, saying it would now require FMTs to involve:
- Donor screenings with questions designed to assess the risk of colonization with drug-resistant bacteria;
- Excluding donations from individuals at a higher risk of colonizing drug-resistant multi-drug resistant organisms; and
- Lab tests for drug-resistant bacteria to identify and exclude stool with drug-resistant bacteria.
Doctors issue report on FMT patients
FDA did not provide many details on the two cases, which led doctors from Massachusetts General Hospital, where the patients were treated, to issue a report detailing the cases. Elizabeth Hohmann, co-author of the report and associate professor of medicine and infectious diseases at Mass General and Harvard Medical School, said, "We wanted to set the record straight."
According to the report, both patients were involved in clinical trials to see if FMTs could be used as a potential therapy for their conditions. One patient was in a trial to learn whether FMTs could help improve brain function in patients with severe liver disease. The other was participating in a trial to see if FMTs could be used to help immune function in leukemia patients who had undergone chemotherapy and stem cell transplants.
Two and a half weeks after doctors administered the final FMT dose to the liver disease patient, a form of E. coli was found in the patient's bloodstream, the report said. The patient recovered after intravenous antibiotics killed the bacteria.
The leukemia patient also developed the same form of drug-resistant E. coli. However, the patient had taken drugs to suppress his immune system as part of a bone marrow transplant and began to decline faster, the report said. Eight days after his last FMT dose, the patient was placed on a ventilator, and two days later the patient died from a severe bloodstream infection, according to the report.
Upon investigation of the liver patient's infection, doctors discovered that the stool sample used for the FMT contained the drug-resistant organism.
According to Hohmann, the stool donor was "what I call a 'screamingly healthy person.' Only about one in 40 people who think they might be healthy enough to [donate stool] actually turn out to meet all of our criteria. [The donor] had none of the 'risk factors' for carrying these organisms. They could not recall the last time they received antibiotics, had zero medical history, no international travel. Plus, they completed all of the other screening tests."
The doctors had been following FDA protocol testing stool donations for infectious bugs, but were not instructed by FDA to test or destroy older stool samples kept in storage, Hohmann said. The stool sample that sickened the two patients in the report had been stored in a freezer for several months.
"It wasn't obvious to a lot of smart people here," Hohmann said. "We didn't think to go back in time."
Hohmann said the report should serve as "a cautionary and sad tale. It points out some of the important medical issues about immune-compromised [patients] and maybe that changing the microbiome is not always a good idea."
Alexander Khoruts, a professor of medicine and medical director of the Microbiota Therapeutics Program at the University of Minnesota who was not involved in the report, said the report should "set off alarm bells for those who thought that [FMTs were] risk free." He added that Mass General "did the right thing" by sharing details and that he hopes the report will lead doctors to be more cautious.
Stuart Johnson, an associate professor of medicine at Loyola University Stritch School of Medicine, who specializes in the bacterial gut infection Clostridium difficile, said he thinks the report "points out that we don't know everything that's in someone's feces, and I think widespread adoption of this practice is problematic" (Carroll, NBC News, 10/30; Jacobs, New York Times, 10/30; Smith, Medium, 10/30).