Recent patient death calls into question viability of effective treatment for recurrent C diff.
Fecal microbiota transplantation (FMT) has attracted mainstream media attention recently as the health care community ponders its longterm viability.
The treatment approach is important, what with Clostridioides difficile infection (CDI, formerly Clostridium) encompassing such a significant public health threat. Figures from the US Centers of Disease Control and Prevention (CDC) suggest that some 500,000 Americans are diagnosed with CDI annually; more than half of these infections are health care-associated.
FMT has now become part of the standard of care for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments, at least per the most recent guidelines from the Infectious Diseases Society of America (IDSA). Multiple clinical trials evaluating the approach have yielded positive results, and a review of outcomes published in Open Forum Infectious Diseases (OFID) notes that it has “the potential to reduce [antibiotic-resistant organism] colonization through restoring microbial community composition and function,” although the authors emphasize that further research is needed.
Still, not all of the news surrounding FMT has been positive. On June 13, 2019, Contagion® reported that 2 patients who had received FMT were sickened by stools containing E coli bacteria that produced extended-spectrum ß-lactamase, which, of course, is resistant to a number of currently available antibiotics. As of this writing, 1 of the 2 patients died as a result. The 2 patients were treated with stools from the same donor, and both were immunocompromised prior to FMT.
Notably, per The New York Times on June 13th, the US Food and Drug Administration (FDA) has opted to suspend a number of clinical trials involving the use of FMT until further notice. FMT has not been approved by the FDA as a treatment for CDI.
“The [FDA] is informing health care providers and patients of the potential risk of serious or life-threatening infections with the use of [FMT],” the agency wrote in a statement released with the announcement. “The agency is now aware of bacterial infections caused by multidrug-resistant organisms…that have occurred…from use of investigational FMT. Patients considering FMT to treat [CDI] should speak to their health care provider to understand the potential risks associated with the product’s use. Because of these serious adverse reactions that occurred with investigational FMT, FDA has determined that…donor screening…and exclusion of individuals at higher risk of colonization with [multidrug-resistant organisms]…should be implemented.”
Although patient safety is paramount, including for those participating in clinical trials, the FDA’s decision could, in effect, hinder efforts to further understand what previously had been considered a promising treatment for a difficult bug.
Michael Woodworth, MD, MSc, assistant professor of infectious diseases at Emory University School of Medicine, and Jennie H. Kwon, DO, MSCi, associate professor in the Division of Infectious Diseases at the John T. Milliken Department of Internal Medicine, Washington University School of Medicine, St. Louis, are co-authors of the OFID paper and are both ID specialists involved in ongoing clinical trials of FMT. Their trials haven’t been affected by the FDA decision, they said, because they use their own donors and bank their own material after it has been screened for antibiotic resistant bacteria.
Woodworth told Contagion® that FMT has not yet been widely used to date because it “is still only being performed by a small number of providers and billing and logistics of obtaining the material for FMT have not been well-integrated into routine clinical practice.”
He continued, “Awareness of the role of FMT and its importance overall is still limited among patients, the lay press, as well as many providers. On one hand, it is appropriate to not suggest that FMT be a first-line therapy, as it is not FDA approved and long-term safety data are still limited. On the other hand, FMT is a treatment that appears highly effective for some conditions and is now recommended in many treatment guidelines for recurrent [CDI]. In other words, I believe that awareness of FMT is growing but enthusiasm in the lay community is outpacing uptake in clinical practice, which could lead to future complications in effective research of safety and efficacy of microbiome therapies.”
According to Woodworth, there are also lingering questions over how the donor stool “material should be regulated [and] how donors should be routinely selected and screened.”
“Microbiome therapies such as FMT are an exciting next step towards the prevention and treatment of disease, [but] we still have many known unknowns and unknown unknowns,” added Kwon. “First and foremost, we need to establish the safety and efficacy of FMT, including recipient and donor selection. We also need a better understanding of the composition of microbial communities that are most beneficial, and work with the appropriate regulatory bodies to ensure the safe and appropriate use of microbiome therapies.”