Stool containing drug-resistant E. coli bacteria killed 73-year-old man, doctors say after first death from fecal transplant
A 73-year-old man became the first to die from a fecal transplant earlier this year. Doctors from Massachusetts General Hospital (MGH), Boston, have now published a detailed report, which explains that the donor stool contained a type of drug-resistant E. coli bacteria that killed the man.
Following the death, the US Food and Drug Administration (FDA) issued a safety alert in June, informing healthcare providers and patients of the potential risk of serious or life-threatening infections with the use of fecal transplant.
The team of doctors from MGH were part of a clinical trial. The details of what happened have now been reported in the journal The New England Journal of Medicine.
“It’s (this type of drug-resistant bacteria) not that rare anymore. This kind of bacteria is increasingly common worldwide,” Dr. Elizabeth Hohmann - physician director of the Partners Human Research Committees (IRBs) and staff physician in the Infectious Diseases Division at MGH - told MEA WorldWide (MEAWW). She is one of the authors of the report.
According to the report, the two immunocompromised adults, who received the fecal transplant, developed infections from an antibiotic-resistant strain of Escherichia coli (E. coli) following transplants from stool contaminated with the bacteria. The patients - a 69-year-old man and a 73-year-old man - were part of two separate clinical trials, but both got transplants from the same stool donor.
“We describe two patients in whom extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli bacteremia occurred after they had undergone FMT (fecal microbiota transplantation) in two independent clinical trials; both cases were linked to the same stool donor by means of genomic sequencing. One of the patients died. Enhanced donor screening to limit the transmission of microorganisms that could lead to adverse infectious events and continued vigilance to define the benefits and risks of FMT across different patient populations is warranted,” says the report.
What is fecal transplant
Referred to as fecal microbiota transplantation (FMT), this is an emerging therapy to treat a type of infection called Clostridium difficile (C. difficile) in patients who do not respond to traditional treatments, say experts. The therapy is also being actively investigated for other conditions. However, the death during the clinical trial shows that it is not without risks.
“ClinicalTrials.gov currently lists more than 300 studies evaluating FMT for various indications, primarily gastrointestinal, but also for neurologic, behavioral, and metabolic conditions,” says the report.
According to the Centers for Disease Control and Prevention (CDC), C. difficile causes life-threatening diarrhea and colitis (inflammation of the colon), mostly in people who have had both recent medical care and antibiotics. An estimated 500,000 Americans suffer from the infection every year, and about 15,000 die from it, says CDC.
Fecal transplants are performed by doctors by transferring the stool of a healthy donor into the gastrointestinal tract of the patient to treat C. difficile. When antibiotics kill off too many "good" bacteria in the digestive tract, fecal transplants can help replenish “bacterial balance,” say experts.
Fecal transplants have not been officially approved by the FDA, which considers it an investigational treatment currently.
“It’s still an important part of the research and a hot new area scientifically for many gastrointestinal conditions and also others outside the gastrointestinal tract,” Dr. Hohmann told MEAWW.
The report
While the 69-year-old man had cirrhosis of the liver due to hepatitis C virus infection, the 73-year-old man had a rare blood condition. The doctors described the 73-year-old’s condition as therapy-related myelodysplastic syndrome. According to Mayo experts, myelodysplastic syndromes are a group of disorders caused by poorly formed blood cells or ones that do not work properly.
“Despite maximum supportive measures, the patient’s condition worsened, and he died from severe sepsis two days later. The final results of blood cultures showed ESBL-producing E. coli,” says the report.
Potential donors and the donated stool are usually tested for harmful bacteria. However, the donor stool and resulting FMT used in these two individuals were not tested for multi-drug-resistant organisms (MDROs), prior to use.
“Donor screening was performed according to the protocols approved by our local institutionalreview board and the Food and Drug Administration (FDA). Donors were adults 18 to 50 years of age,” says the report.
The FMT capsules that were administered to the two patients were manufactured in November 2018. In January 2019, in response to a regulatory review by the FDA of a separate trial, the donor-stool screening was expanded by MGH experts to include tests for extended-spectrum beta-lactamase (ESBL)-producing organisms.
In their report, the team says, “These serious adverse events were promptly reported to the FDA and supervising institutional review boards. Our trials were halted, and the FDA placed a national alert on its website and mandated additional screening for those conducting FMT research under FDA supervision.”
They further say, “During the donation period, volunteers underwent an interim health query for febrile, systemic, and gastrointestinal symptoms and were deferred for any change in health status. All donations were stored and not used for an additional four weeks to allow retesting for certain infections that have a longer incubation period.”
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.
“We report two cases of bacteremia caused by an organism that was transmitted through FMT, as shown by means of genome sequencing. The stool donor had no risk factors of multidrug-resistant organism carriage and had donated fecal material before we included routine tests for ESBL-producing organisms in our donor-screening protocol. Given that the frozen capsules from all preparations derived from this donor were positive on ESBL screening, it is likely that this donor material would have been disqualified if screened before donation,” says the report.
The FDA, in its alert, stated that patients considering FMT to treat C. difficile infection should speak to their healthcare provider to understand the potential risks associated with the product’s use. The agency also recommended screening donors to check if they are at risk of carrying multi-drug-resistant organisms, as well as testing of donor stool for multi-drug resistant organisms.
Dr. Hohmann told MEAWW that while such screening will “minimize this problem, but probably not all problems.” “Transmission of unwanted organisms and resistance genes is still a concern and risk,” she told MEAWW.
The team states in the report that despite the infectious complications, the benefits of FMT should be balanced with the associated risks when considering treatment options for patients with “recurrent or refractory” C. difficile infection.
“Ongoing assessment of the risks and benefits of FMT research is needed, as are continuing efforts to improve donor screening to limit transmission of microorganisms that could lead to adverse infectious events,” says the report.