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Officials at the Food and Drug Administration have issued a safety alert regarding the use of fecal microbiota for transplantation (FMT) and the risk of serious adverse reactions because of transmission of multidrug-resistant organisms (MDROs).
According to the alert, which was issued on June 13, 2019, the agency became aware of two immunocompromised adult patients who received investigational FMT and developed infections caused by extended-spectrum beta-lactamase (EBSL)–producing Escherichia coli. One of the patients died.
“This is certainly a theoretical risk that we’ve known about,” Lea Ann Chen, MD, a gastroenterologist at New York University, said in an interview. “This announcement is important, because we probably don’t counsel patients specifically about this risk. We say there is a risk for transmission of infectious agents in general, but I think that probably very few counsel patients about a risk for transmission of MDROs.”
The donor stool and FMT used in the two patients were not tested for ESBL-producing gram-negative organisms prior to use. As a result of these serious adverse reactions, the FDA has determined that certain donor screening and stool testing protections are needed for any investigational use of FMT. On June 18, the agency released an additional statement, which stipulated that all Investigational New Drug (IND) holders must implement the following new requirements no later than July 15, 2019:
“1. Donor screening must include questions that specifically address risk factors for colonization with MDROs, and individuals at higher risk of colonization with MDROs must be excluded from donation. Examples of persons at higher risk for colonization with MDROs include:
a. Health care workers
b. Persons who have recently been hospitalized or discharged from long-term care facilities
c. Persons who regularly attend outpatient medical or surgical clinics
d. Persons who have recently engaged in medical tourism
2. FMT donor stool testing must include MDRO testing to exclude use of stool that tests positive for MDRO. The MDRO tests should at minimum include extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Culture of nasal or perirectal swabs is an acceptable alternative to stool testing for MRSA only. Bookend testing (no more than 60 days apart) before and after multiple stool donations is acceptable if stool samples are quarantined until the post-donation MDRO tests are confirmed negative.
3. All FMT products currently in storage for which the donor has not undergone screening and stool testing for MDROs as described above must be placed in quarantine until such time as the donor is confirmed to be not at increased risk of MDRO carriage and the FMT products have been tested and found negative. In the case of FMT products manufactured using pooled donations from a single donor, stored samples of the individual donations prior to pooling must be tested before the FMT products can be administered to subjects.
4.The informed consent process for subjects being treated with FMT product under your IND going forward should describe the risks of MDRO transmission and invasive infection as well as the measures implemented for donor screening and stool testing.”
On June 14, the American Gastroenterological Association sent a communication about the FDA alert to its members, which stated that the AGA “is committed to advancing applications of the gut microbiome. Our top priority is ensuring patient safety from microbiome-based therapeutics, such as FMT. Through the AGA FMT National Registry, AGA is working with physicians and patients to track FMT usage, patient outcomes and adverse events. Associated with the registry is a biorepository of donor and patient stool samples, which will allow further investigation of unexpected events such as those described in FDA’s safety alert.”
Dr. Chen, who received the AGA Research Foundation’s 2016 Research Scholar Award for her work on the gut microbiome and inflammatory bowel disease, pointed out that FMT has also been studied as a way to prevent colonization and infection with certain drug resistant organisms, such as VRE.
“Therefore, it’s not that FMT is ‘bad;’ we just have to be more diligent about optimizing the safety of the procedure by screening for of multidrug-resistant organisms,” she said. “We also need to study the use of FMT more, so that we can fully understand the risks associated with the procedure. It’s an important and potentially lifesaving procedure for some, but it’s important that everyone go into the procedure understanding fully what the risks and benefits are.”
Suspected adverse events related to the administration of FMT products can be reported to the FDA at 1-800-332-1088 or via MedWatch.
Officials at the Food and Drug Administration have issued a safety alert regarding the use of fecal microbiota for transplantation (FMT) and the risk of serious adverse reactions because of transmission of multidrug-resistant organisms (MDROs).
According to the alert, which was issued on June 13, 2019, the agency became aware of two immunocompromised adult patients who received investigational FMT and developed infections caused by extended-spectrum beta-lactamase (EBSL)–producing Escherichia coli. One of the patients died.
“This is certainly a theoretical risk that we’ve known about,” Lea Ann Chen, MD, a gastroenterologist at New York University, said in an interview. “This announcement is important, because we probably don’t counsel patients specifically about this risk. We say there is a risk for transmission of infectious agents in general, but I think that probably very few counsel patients about a risk for transmission of MDROs.”
The donor stool and FMT used in the two patients were not tested for ESBL-producing gram-negative organisms prior to use. As a result of these serious adverse reactions, the FDA has determined that certain donor screening and stool testing protections are needed for any investigational use of FMT. On June 18, the agency released an additional statement, which stipulated that all Investigational New Drug (IND) holders must implement the following new requirements no later than July 15, 2019:
“1. Donor screening must include questions that specifically address risk factors for colonization with MDROs, and individuals at higher risk of colonization with MDROs must be excluded from donation. Examples of persons at higher risk for colonization with MDROs include:
a. Health care workers
b. Persons who have recently been hospitalized or discharged from long-term care facilities
c. Persons who regularly attend outpatient medical or surgical clinics
d. Persons who have recently engaged in medical tourism
2. FMT donor stool testing must include MDRO testing to exclude use of stool that tests positive for MDRO. The MDRO tests should at minimum include extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Culture of nasal or perirectal swabs is an acceptable alternative to stool testing for MRSA only. Bookend testing (no more than 60 days apart) before and after multiple stool donations is acceptable if stool samples are quarantined until the post-donation MDRO tests are confirmed negative.
3. All FMT products currently in storage for which the donor has not undergone screening and stool testing for MDROs as described above must be placed in quarantine until such time as the donor is confirmed to be not at increased risk of MDRO carriage and the FMT products have been tested and found negative. In the case of FMT products manufactured using pooled donations from a single donor, stored samples of the individual donations prior to pooling must be tested before the FMT products can be administered to subjects.
4.The informed consent process for subjects being treated with FMT product under your IND going forward should describe the risks of MDRO transmission and invasive infection as well as the measures implemented for donor screening and stool testing.”
On June 14, the American Gastroenterological Association sent a communication about the FDA alert to its members, which stated that the AGA “is committed to advancing applications of the gut microbiome. Our top priority is ensuring patient safety from microbiome-based therapeutics, such as FMT. Through the AGA FMT National Registry, AGA is working with physicians and patients to track FMT usage, patient outcomes and adverse events. Associated with the registry is a biorepository of donor and patient stool samples, which will allow further investigation of unexpected events such as those described in FDA’s safety alert.”
Dr. Chen, who received the AGA Research Foundation’s 2016 Research Scholar Award for her work on the gut microbiome and inflammatory bowel disease, pointed out that FMT has also been studied as a way to prevent colonization and infection with certain drug resistant organisms, such as VRE.
“Therefore, it’s not that FMT is ‘bad;’ we just have to be more diligent about optimizing the safety of the procedure by screening for of multidrug-resistant organisms,” she said. “We also need to study the use of FMT more, so that we can fully understand the risks associated with the procedure. It’s an important and potentially lifesaving procedure for some, but it’s important that everyone go into the procedure understanding fully what the risks and benefits are.”
Suspected adverse events related to the administration of FMT products can be reported to the FDA at 1-800-332-1088 or via MedWatch.
Officials at the Food and Drug Administration have issued a safety alert regarding the use of fecal microbiota for transplantation (FMT) and the risk of serious adverse reactions because of transmission of multidrug-resistant organisms (MDROs).
According to the alert, which was issued on June 13, 2019, the agency became aware of two immunocompromised adult patients who received investigational FMT and developed infections caused by extended-spectrum beta-lactamase (EBSL)–producing Escherichia coli. One of the patients died.
“This is certainly a theoretical risk that we’ve known about,” Lea Ann Chen, MD, a gastroenterologist at New York University, said in an interview. “This announcement is important, because we probably don’t counsel patients specifically about this risk. We say there is a risk for transmission of infectious agents in general, but I think that probably very few counsel patients about a risk for transmission of MDROs.”
The donor stool and FMT used in the two patients were not tested for ESBL-producing gram-negative organisms prior to use. As a result of these serious adverse reactions, the FDA has determined that certain donor screening and stool testing protections are needed for any investigational use of FMT. On June 18, the agency released an additional statement, which stipulated that all Investigational New Drug (IND) holders must implement the following new requirements no later than July 15, 2019:
“1. Donor screening must include questions that specifically address risk factors for colonization with MDROs, and individuals at higher risk of colonization with MDROs must be excluded from donation. Examples of persons at higher risk for colonization with MDROs include:
a. Health care workers
b. Persons who have recently been hospitalized or discharged from long-term care facilities
c. Persons who regularly attend outpatient medical or surgical clinics
d. Persons who have recently engaged in medical tourism
2. FMT donor stool testing must include MDRO testing to exclude use of stool that tests positive for MDRO. The MDRO tests should at minimum include extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Culture of nasal or perirectal swabs is an acceptable alternative to stool testing for MRSA only. Bookend testing (no more than 60 days apart) before and after multiple stool donations is acceptable if stool samples are quarantined until the post-donation MDRO tests are confirmed negative.
3. All FMT products currently in storage for which the donor has not undergone screening and stool testing for MDROs as described above must be placed in quarantine until such time as the donor is confirmed to be not at increased risk of MDRO carriage and the FMT products have been tested and found negative. In the case of FMT products manufactured using pooled donations from a single donor, stored samples of the individual donations prior to pooling must be tested before the FMT products can be administered to subjects.
4.The informed consent process for subjects being treated with FMT product under your IND going forward should describe the risks of MDRO transmission and invasive infection as well as the measures implemented for donor screening and stool testing.”
On June 14, the American Gastroenterological Association sent a communication about the FDA alert to its members, which stated that the AGA “is committed to advancing applications of the gut microbiome. Our top priority is ensuring patient safety from microbiome-based therapeutics, such as FMT. Through the AGA FMT National Registry, AGA is working with physicians and patients to track FMT usage, patient outcomes and adverse events. Associated with the registry is a biorepository of donor and patient stool samples, which will allow further investigation of unexpected events such as those described in FDA’s safety alert.”
Dr. Chen, who received the AGA Research Foundation’s 2016 Research Scholar Award for her work on the gut microbiome and inflammatory bowel disease, pointed out that FMT has also been studied as a way to prevent colonization and infection with certain drug resistant organisms, such as VRE.
“Therefore, it’s not that FMT is ‘bad;’ we just have to be more diligent about optimizing the safety of the procedure by screening for of multidrug-resistant organisms,” she said. “We also need to study the use of FMT more, so that we can fully understand the risks associated with the procedure. It’s an important and potentially lifesaving procedure for some, but it’s important that everyone go into the procedure understanding fully what the risks and benefits are.”
Suspected adverse events related to the administration of FMT products can be reported to the FDA at 1-800-332-1088 or via MedWatch.