New donor screening protocols for clinical trials involving fecal microbiota transplantation

Back in May, I wrote a blog post about fecal microbiota transplantation (FMT), or stool transplantation. FMT is considered standard-of-care therapy to treat recurrent Clostridium difficile (C. diff) infections. In this procedure, stool from a healthy donor is placed into the gut of a patient, usually via colonoscopy, to restore helpful bacteria that help protect against recurrent C. diff infection (rCDI).

An important event occurred after my initial post. On June 13, 2019, the FDA issued a safety alert concerning the risk of transmission of multi-drug resistant organisms (MDRO) through FMT. MDROs are bacteria that are resistant to one or more antibiotics.

Safety alert leaves many questions unanswered

The safety alert was issued in response to the transmission of a specific MDRO from donor stool into two patients following FMT. Tragically, one of these individuals died. The FDA announcement provides very few details regarding these cases, and it does not provide information on the cause of this patient's death. What is known is that these two patients were given FMT as part of a research protocol and not as part of clinical care to treat rCDI.

As I mentioned in my previous post, FMT is supported by guidelines, but is still considered investigational and is not currently FDA-approved. FMT can be performed for clinical care to treat rCDI. But an FMT for any other indication can only be performed in the setting of a clinical trial.

The FDA has not yet disclosed the indication or reason for the FMT for the two patients mentioned in their safety alert, but the FDA did note that the patients were immunocompromised. FMT has been shown to be safe in immunocompromised patients, but generally these patients are at increased risk for infections. Additionally, it was noted that the donor material used in this research protocol had not been screened for MDROs.

FDA institutes new screening requirement for donor stool

Following this event, the FDA now requires MDRO screening for donor stool for all active and future FMT study protocols. Worldwide, screening is being recommended for clinical protocols as well, and this is expected to be supported by an upcoming guideline.

It is important to note that all major stool banks in the US and around the world had implemented screening protocols to detect MDROs and exclude potential donors who test positive well prior to this event. This includes OpenBiome, a large, non-profit stool bank that is widely used in the US and has provided over 45,000 treatments.

Prior to this there had been no previous transmissions of MDROs reported, highlighting that this procedure still remains very safe overall. That being said, this event highlights the need for adherence to standardized screening protocols, which is key for patient safety.

The FDA has reached out to sites that have ongoing FMT protocols to ensure appropriate screening procedures are being followed. Any protocols not utilizing appropriate screening practices were put on hold. The FDA has not released any further information about how many protocols or sites were affected by this step.

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