In June, the Food and Drug Administration announced that one patient had died and another was sickened from a fecal transplant, spurring the agency to set new safety guidelines for the procedure. But the announcement, which offered little information on the two cases, left doctors clamoring for more details.
A report published Wednesday in the New England Journal of Medicine fills in the gaps. It was written by doctors from the Massachusetts General Hospital, where the two patients had been participating in two separate clinical trials involving fecal microbiota transplants, or FMTs.
“We wanted to set the record straight,” said co-author Dr. Elizabeth Hohmann, an associate professor of medicine and infectious diseases at Massachusetts General Hospital and Harvard Medical School.
FMTs were originally developed to treat patients with life-threatening diarrhea caused by infections with Clostridium difficile, a nasty bacterium that can overwhelm the gut if a person takes too many antibiotics. By transplanting microorganisms from a donor’s stool, the procedure can restore healthy bacteria to the gut.
However, FMTs are now being explored in clinical trials as a potential therapy for a wide range of conditions, including inflammatory bowel disease, liver disease, obesity and multiple sclerosis.
One of the patients described in the new report was given FMT in a trial to learn whether the treatment could help improve brain function in people with severe liver disease.
People with late liver failure can develop brain problems that affect thinking, Hohmann said. These patients also have very altered gut bacteria, and one hypothesis is that compounds created by these gut microbes can get into the bloodstream and affect the brain, she said.
Two and a half weeks after the patient’s last FMT dose, a form of E. coli resistant to multiple drugs was found in the patient’s bloodstream. Intravenous antibiotics killed off the bacteria and the patient recovered. When the researchers investigated the source of the patient’s infection, they discovered that the stool sample used for the FMT contained the multidrug-resistant organism.
As it turns out, that same donor stool had also been used in another patient, one who was participating in a different clinical trial. That trial was looking at using FMT in leukemia patients who had received chemotherapy and stem cell transplants to rebuild their immune systems.
One of the risks of this leukemia treatment is, as the immune system rebuilds with the donated stem cells, it can turn on the patient’s own body, in what’s known as graft versus host disease. Researchers hope that by normalizing the gut microbes through FMT, this bootup of the new immune system might go more smoothly, Hohmann said.
These patients tend to have abnormal microbiomes, Hohmann said, in part because leukemia treatment makes them prone to infections and as a result, they receive a lot of antibiotics.
This is a cautionary and sad tale.
But this patient developed the same life-threatening infection with drug-resistant E. coli shortly after FMT was finished. Indeed, the same type of E. coli from the same stool donor was found in the patient’s bloodstream, testing revealed. Despite aggressive treatment, Hohmann and her colleagues wrote, they weren’t able to save the patient.
“This is a cautionary and sad tale,” Hohmann told NBC News. “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.”
Following the patient death, the FDA announced guidelines requiring that both donors and their stool be screened for multidrug-resistant organisms, including the one implicated in these two cases. But it’s important to remember that there may be other such organisms out there that aren’t being screened for, Hohmann said. “We can increase the ways we look for this, but we can’t 100 percent eliminate it,” she added.
Dr. Alexander Khoruts, a professor of medicine and the medical director of the Microbiota Therapeutics Program at the University of Minnesota, said that the new report should “set off alarm bells for those who thought that this was risk free.”
The Massachusetts General Hospital researchers “did the right thing” by sharing the details, he said.
Khoruts added that he hopes the report will spur physicians and researchers to proceed with more caution when it comes to FMTs, and to recognize that the field is far more complicated than they might have thought.