Death after cocoa transplant gone wrong, warns FDA

One patient died and another became seriously ill after a fecal transplant that inadvertently seeded their bowels with a multidrug-resistant bacterial infection, warned the Food and Drug Administration.

The cases highlight the serious risks of what some consider a relatively safe procedure. They are also eliminating the malignant problems of federal surveillance for experimental transplants, which the FDA has attempted to regulate. In his warning Thursday, the agency announced new protections for testing and experimental uses of the procedure.

The FDA has shared little details about deadly transplants. His warning only noted that the cases involved two immunocompromised patients prior to experimental transplants who received stool from the same donor. After the transplant, patients developed invasive infections from a E. coli strain resistant to a wide variety of penicillin and cephalosporin antibiotics. the E. coli The strain carried an anti-drug enzyme called extended-spectrum beta-lactamase (ESBL), which usually cleaves a ring common to all the chemical structures of these antibiotics. When the unnamed researchers who administered the transplant examined the stool of the donor, they found that the stool contained an identical product producing ESBL. E. coli.

One of the patients has died and the fate of the other has not been discussed. The agency also did not explain how and why patients were immunocompromised before transplants, or what transplants were trying to accomplish, how they had been performed, who had driven them or when they had occurred.

Pootential

In general, fecal transplants (fecal microbiota for transplantation or FMT) are intended to replace or replenish the microbial communities that develop in the intestinal tract. These microbial communities are thought to influence various health factors, such as food degradation, cyclic hormone function, modulation of the immune response, and protection against hostile invaders. But these microbial communities can be crushed or imbalanced (dysbiosis) by disturbances such as powerful antibiotic treatments or particularly stubborn pathogens.

The researchers hypothesized that the stools of healthy, microbe-laden donors could restore the balance and beneficial functions of the microbiome in some patients, possibly through complete repopulation of the gut microbiota or an increase in microbiota. microbial diversity. Studies have shown that this is the case of people with intractable intestinal infections caused by diarrhea. Clostridium difficile bacteria. Some trials have shown that MSDs can cure 80% to 90% of these infections, although their functioning is not yet clear. FMT-based treatments for other conditions, such as obesity, cancer or immune disorders, remain hypothetical.

Mucky's methods

Also experimental is the way forward for a FMT. The researchers used hand-mixed fresh stools, freeze-dried nuggets, microbe-enriched excrements, and fully synthetic suspensions. Delivery methods included simple enemas, colonoscopies, capsules filled with poop that are swallowed and tubes threaded into the nose up to the stomach.

All of this posed a delicate regulatory problem for the FDA. The agency considers the transplanted feces as a medicine and asserted its regulatory authority as such. But FMTs undermine the rules used to regulate standard medicines, which tend to contain highly controlled and identifiable active ingredients that can be carefully quantified, formulated, standardized and tested.

Leaving aside transplantation methods, how to control, quantify and normalize poo? This is particularly difficult because it is still unclear what characteristics (if any) of feces are or could be therapeutic. Are specific microbial strains essential? Or combinations? Or concentrations? Everything is still undetermined. And unlike conventional pharmaceuticals, purposefully concocted, excreta can contain potentially harmful components, such as pathogens and toxins. How should we filter the poop for those?

In July 2013, the FDA held a public workshop on the intimidating topic, based on input from researchers, physicians, companies and the public. The agency took the heavy decision of regulating the FMTs with a slight touch until more data became available. As the agency says, she decided to exercise a "discretionary power of execution".

With the announcement on Thursday, the role of the agency has strengthened a little. The agency now claims that FMT stool donors and stools themselves should be screened for the presence of MDR-TB and excluded organisms, if they do. An FDA regulator told the New York Times that the agency also suspended clinical trials involving FMTs until it was clear that they had such safety precautions. The regulator has not specified the number of pending clinical trials, but clinicaltrials.gov has identified several dozen active trials of FMTs.