Fecal Microbiota Transplant Offers Hope to Immunocompromised Patients

By: Michael Ferguson
Wednesday, December 10, 2014

There seemed to be no options. After undergoing an organ transplant, the patient was prescribed high-dose immunosuppressants, which facilitated acceptance of the donated organ but also crippled the patient’s infection-fighting mechanisms. The muted immune response allowed Clostridium difficile (C. diff) bacteria to disrupt the patient’s gut bacterial balance.

For one year, the patient suffered multiple recurrences of C. diff infection (CDI), resulting in repeated hospitalizations. Following a six- to eight-week hospital stay due to continuous diarrhea related to CDI, the patient was referred to Colleen R. Kelly, MD, Assistant Professor of Medicine at The Warren Alpert Medical School of Brown University and gastroenterologist at Women’s Medicine Collaborative.

Having performed fecal microbiota transplant (FMT) as a curative therapy for CDI in otherwise healthy patients, Dr. Kelly was prepared to offer the same treatment to this patient. A colleague who specializes in infectious disease cautioned against FMT in this case, citing the presumably increased risk to patients on immunosuppressants. However, the patient would die if the CDI persisted, so Dr. Kelly performed the procedure.

Bacterial Ecology

Repeated cycles of antibiotics can disrupt the balance of native bacterial flora, allowing vicious bacteria to proliferate and cause serious infections, such as CDI. Dr. Kelly’s experience using FMT to treat otherwise healthy patients led her to believe the therapy would be effective and safe for the immunocompromised patient as well.

Bacteria 250

“Your colon has trillions of bacteria in it, and [most] people walking around aren’t infecting themselves from the bacteria they carry,” Dr. Kelly says. “So I hypothesized that doing FMT would restore the gut bacteria to a more normal state and [immunocompromised patients] wouldn’t necessarily be at any increased risk of having those bacteria translocate out of the gut into other parts of the body and cause infection.”

That hypothesis was borne out when the patient enjoyed rapid, significant and lasting improvement. Nor was that an isolated success. A recent multicenter, retrospective study shows FMT effectively treats CDI in immunocompromised patients.

Informing the Decision

While studies suggest FMT is the most effective treatment for recurrent or refractory CDI not effectively treated with standard-of-care antibiotics — such as vancomycin, metronidazole or fidaxomicin — the idea of treating a virulent infection by transplanting bacteria-laden fecal material prevents many physicians from considering FMT a viable option for immunocompromised patients. But the fact that no clinical trials had explored how this patient population tolerates FMT led Dr. Kelly to question that stance.

“When I first started [performing fecal microbiota transplant], nobody was doing it. Now it’s catching on, and people are starting to understand that this really is a way of helping patients. We still have a ways to go. Patients still travel to me because physicians are afraid to do it. They’re afraid of the unknowns — where to start or how to perform it. [Many] still hold back because of safety concerns.”
— Colleen R. Kelly, MD, Assistant Professor of Medicine at The Warren Alpert Medical School of Brown University and gastroenterologist at Women’s Medicine Collaborative

“We didn’t have any data on FMT used on immunocompromised people,” she says. “I started asking physicians who did FMT on these [patients], and I realized there is a lot of experience out there.”

Dr. Kelly and her collaborators at 16 centers reviewed their own case records of 99 patients who underwent FMT, and they published results in The American Journal of Gastroenterology. Eighty patients qualified as immunocompromised because of inflammatory bowel disease, solid organ transplant, oncologic conditions, HIV/AIDS or other conditions.

At issue was the residual strength of their immune systems.

“We are putting a lot of … bacteria into these people who are immunocompromised,” Dr. Kelly says. “The question is: ‘Is their immune system still adequately able to keep those bacteria from going from their colon … into their bloodstream and causing other infections?’”

As the study demonstrated, migratory infections did not occur.

Judicious Application

Despite those outcomes, patient selection remains crucial because severely immunocompromised patients — such as those who have had bone marrow transplant — likely won’t have strong enough immune function to suppress infection.

Additionally, while the study demonstrated FMT is successful even in immunocompromised patients, Dr. Kelly cautions against using the therapy in certain situations, such as when a patient’s life expectancy is limited. Other strategies, such as indefinite vancomycin regimens, may be more suitable.

Caution in the use of FMT is also warranted when patients have a number of comorbidities that contraindicate colonoscopy.

For example, the team reviewed the case of a patient who had an advanced malignancy and severe CDI. The patient was cachectic and near death. Previously, the patient had an unsuccessful FMT, and the physician decided to perform a second to relieve the CDI and improve quality of life. While sedated during the colonoscopy used to perform the FMT, the patient aspirated and later died.

In such cases, hospice may address patient needs better than invasive procedures to alleviate CDI, Dr. Kelly says. Alternatively, less invasive methods for FMT, such as sigmoidoscopy, may prove effective in patients who have significant comorbidities but are not near death.