Fecal transplant found effective, safe in immunocompromised patients

SAN DIEGO – Fecal microbiota transplantation is effective and safe for treating Clostridium difficile infection in immunocompromised patients, according to a retrospective study of 66 patients treated in the United States and Canada.

The final cure rate after one or two fecal microbiota transplantation (FMT) procedures was 89%, first author Dr. Chioma Ihunnah reported at the annual meeting of the American College of Gastroenterology.

There were no infectious complications, but about 10% of patients with inflammatory bowel disease (IBD) had a flare. One patient with severe C. difficile infection died as a result of aspiration during the procedure, but there were no deaths directly related to the fecal microbiota.

"This series demonstrates the effective use of fecal microbiota transplantation for C. diff infection in immunocompromised patients. The rate of cure observed in this study is similar to rates observed in similar studies of immunocompetent patients," said Dr. Ihunnah, a second-year resident in internal medicine at Brown University in Providence, R.I.

"Prospective studies of FMT in immunocompromised patients are needed to confirm efficacy and safety in this population. Additionally, the creation of a national registry for monitoring short- and long-term adverse events after FMT would better provide understanding of patient characteristics that may ultimately correlate with safety and efficacy of FMT," she added.

Session attendee Dr. Samir Shah, also of Brown University, said, "I am curious. There are no guidelines for what we do with our IBD patients with C. diff as far as their medicine. Did you have any protocols to continue medicines or stop medicines, or was it center specific?"

Continuation of antibiotics appeared largely center specific, although analyses are still ongoing, Dr. Ihunnah replied. "The IBD-specific medications were continued, to our knowledge. It was limited to what [data] the centers sent us, but to our knowledge, they were all continued."

In a related press briefing, Dr. Colleen R. Kelly, a study coauthor and a clinical assistant professor at Brown, said that although FMT generally appears to be safe, there have been concerns that complications are underreported.

"We focused on immunocompromised patients because our feeling was that if anybody was going to have a problem with getting an infection or another problem from FMT, that it would be this particular group of patients," she explained, as feces are rich in microorganisms. "There were some worries that some of these very severely immunocompromised patients could get sepsis or could get very ill. And that doesn’t seem to be the case."

The patient who died had a severe C. difficile infection and experienced aspiration during sedation for FMT via colonoscopy. "It maybe brings up the idea that in sicker patients, to just carefully look at the route of administration that you choose to administer FMT and use the least invasive, safest route possible," she said.

The future appears bright for improvements in FMT, such as delivery by pill and tailoring of the material administered, according to Dr. Kelly.

"We won’t be using whole stool a few years from now," she predicted. "There are people who are looking very hard at finding what is the active ingredient, what are the key species, one or more bacteria, that we need to restore this diversity to the flora ... There are companies working on it right now, and with this kind of evidence behind it, to develop a pill that could potentially be used to treat millions of people rather than the 130 people I’ve been able to treat over the last 5 years by conventional means. I really look forward to all of these blends and formulations that are coming around the corner."

Press briefing moderator Dr. Michael E. Cox, of Mercy Medical Center in Baltimore, noted that his center has experienced some failures of FMT that appeared to occur when patients resumed antibiotic therapy. "Do you counsel your patients not to go on antibiotics for a set period of time?" he asked.

Patients receive a lot of counseling tailored at reducing inappropriate use of antibiotics and, when antibiotics are absolutely needed, those that are less likely to trigger a recurrence are selected, Dr. Kelly said. But recurrences of C. difficile infection have been rare in their experience. "I do have them take probiotics during future courses of antibiotics. There is a little bit of data that that can be protective," she noted.

Dr. Kelly cautioned against rushing to use FMT to treat conditions such as IBD, irritable bowel syndrome, and autism. "There are all these diseases where there is thought to be intestinal dysbiosis, and there is this real hope that fecal transplant is going to cure it all. And I just really throw up a big caution that we are not there with any of these other conditions at this point. And to treat those conditions with fecal transplant outside of a clinical trial, really, I don’t think, is right," she maintained.

"That probably bears repeating," commented press briefing discussant Dr. Brian E. Lacy, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. "So if somebody came to you and said, right now, what do you think are the best indications for FMT, what would your answer be?"

"Recurrent C. difficile infection or refractory C. difficile infection – people who aren’t getting better on antibiotics," Dr. Kelly replied.

"Some would say severe C. difficile infection, but that’s another place where I’d probably say there is a yellow light of caution, because in my experience, we have treated very few patients with severe C. diff infection. They don’t appear to do as well," she continued. "They are also much more complicated; they are very sick, patients in the intensive care unit with toxic megacolon. The standard of care in these patients in 2013 is a surgical colectomy."

In the study, the investigators reviewed data collected from 16 centers performing FMT for recurrent, refractory, severe, or complicated C. difficile infection.

Analyses were restricted to immunocompromised patients who underwent the procedure and had at least 12 weeks of follow-up. Overall, 92% of the patients were adults, with a mean age of 53 years (range, 20-82 years). Sixty-two percent of the patients were men.

The reason for immunocompromise was use of immunosuppressive medications for IBD in 48% of patients, receipt of a solid organ transplant in 21%, a chronic medical condition and/or use of other immunosuppressive medication in 18%, cancer or its treatment in 9%, and HIV/AIDS in 3%.

The C. difficile infection was recurrent in 54% of cases, refractory in 12%, and severe or complicated in 34%.

The large majority of the patients (78%) underwent their FMT procedure in the outpatient setting. On average, the mean follow-up was 12 months (range, 3-51 months).

The results showed that 52 patients did not have any recurrence of C. difficile infection within 12 weeks of FMT, reported Dr. Ihunnah. Nine of the patients who had a recurrence underwent a second FMT, and seven of them did not have any additional recurrences. The final cure rate was therefore 89%.

Overall, nine patients (14%) had a serious adverse event within 12 weeks of their FMT: There were seven unplanned hospitalizations (most commonly due to a flare of IBD) and two deaths (one due to worsening of preexisting pneumonia unrelated to FMT and the one due to aspiration).

Nonserious adverse events included two cases of self-limited diarrhea in which no pathogen was identified, four cases of mild abdominal discomfort, one case of minor mucosal tear, and two cases of colectomy among patients with ulcerative colitis performed more than 100 days after FMT.

Dr. Ihunnah and Dr. Kelly disclosed no relevant conflicts of interest.

SAN DIEGO – Fecal microbiota transplantation is effective and safe for treating Clostridium difficile infection in immunocompromised patients, according to a retrospective study of 66 patients treated in the United States and Canada.

The final cure rate after one or two fecal microbiota transplantation (FMT) procedures was 89%, first author Dr. Chioma Ihunnah reported at the annual meeting of the American College of Gastroenterology.

There were no infectious complications, but about 10% of patients with inflammatory bowel disease (IBD) had a flare. One patient with severe C. difficile infection died as a result of aspiration during the procedure, but there were no deaths directly related to the fecal microbiota.

"This series demonstrates the effective use of fecal microbiota transplantation for C. diff infection in immunocompromised patients. The rate of cure observed in this study is similar to rates observed in similar studies of immunocompetent patients," said Dr. Ihunnah, a second-year resident in internal medicine at Brown University in Providence, R.I.

"Prospective studies of FMT in immunocompromised patients are needed to confirm efficacy and safety in this population. Additionally, the creation of a national registry for monitoring short- and long-term adverse events after FMT would better provide understanding of patient characteristics that may ultimately correlate with safety and efficacy of FMT," she added.

Session attendee Dr. Samir Shah, also of Brown University, said, "I am curious. There are no guidelines for what we do with our IBD patients with C. diff as far as their medicine. Did you have any protocols to continue medicines or stop medicines, or was it center specific?"

Continuation of antibiotics appeared largely center specific, although analyses are still ongoing, Dr. Ihunnah replied. "The IBD-specific medications were continued, to our knowledge. It was limited to what [data] the centers sent us, but to our knowledge, they were all continued."

In a related press briefing, Dr. Colleen R. Kelly, a study coauthor and a clinical assistant professor at Brown, said that although FMT generally appears to be safe, there have been concerns that complications are underreported.

"We focused on immunocompromised patients because our feeling was that if anybody was going to have a problem with getting an infection or another problem from FMT, that it would be this particular group of patients," she explained, as feces are rich in microorganisms. "There were some worries that some of these very severely immunocompromised patients could get sepsis or could get very ill. And that doesn’t seem to be the case."

The patient who died had a severe C. difficile infection and experienced aspiration during sedation for FMT via colonoscopy. "It maybe brings up the idea that in sicker patients, to just carefully look at the route of administration that you choose to administer FMT and use the least invasive, safest route possible," she said.

The future appears bright for improvements in FMT, such as delivery by pill and tailoring of the material administered, according to Dr. Kelly.

"We won’t be using whole stool a few years from now," she predicted. "There are people who are looking very hard at finding what is the active ingredient, what are the key species, one or more bacteria, that we need to restore this diversity to the flora ... There are companies working on it right now, and with this kind of evidence behind it, to develop a pill that could potentially be used to treat millions of people rather than the 130 people I’ve been able to treat over the last 5 years by conventional means. I really look forward to all of these blends and formulations that are coming around the corner."

Press briefing moderator Dr. Michael E. Cox, of Mercy Medical Center in Baltimore, noted that his center has experienced some failures of FMT that appeared to occur when patients resumed antibiotic therapy. "Do you counsel your patients not to go on antibiotics for a set period of time?" he asked.

Patients receive a lot of counseling tailored at reducing inappropriate use of antibiotics and, when antibiotics are absolutely needed, those that are less likely to trigger a recurrence are selected, Dr. Kelly said. But recurrences of C. difficile infection have been rare in their experience. "I do have them take probiotics during future courses of antibiotics. There is a little bit of data that that can be protective," she noted.

Dr. Kelly cautioned against rushing to use FMT to treat conditions such as IBD, irritable bowel syndrome, and autism. "There are all these diseases where there is thought to be intestinal dysbiosis, and there is this real hope that fecal transplant is going to cure it all. And I just really throw up a big caution that we are not there with any of these other conditions at this point. And to treat those conditions with fecal transplant outside of a clinical trial, really, I don’t think, is right," she maintained.

"That probably bears repeating," commented press briefing discussant Dr. Brian E. Lacy, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. "So if somebody came to you and said, right now, what do you think are the best indications for FMT, what would your answer be?"

"Recurrent C. difficile infection or refractory C. difficile infection – people who aren’t getting better on antibiotics," Dr. Kelly replied.

"Some would say severe C. difficile infection, but that’s another place where I’d probably say there is a yellow light of caution, because in my experience, we have treated very few patients with severe C. diff infection. They don’t appear to do as well," she continued. "They are also much more complicated; they are very sick, patients in the intensive care unit with toxic megacolon. The standard of care in these patients in 2013 is a surgical colectomy."

In the study, the investigators reviewed data collected from 16 centers performing FMT for recurrent, refractory, severe, or complicated C. difficile infection.

Analyses were restricted to immunocompromised patients who underwent the procedure and had at least 12 weeks of follow-up. Overall, 92% of the patients were adults, with a mean age of 53 years (range, 20-82 years). Sixty-two percent of the patients were men.

The reason for immunocompromise was use of immunosuppressive medications for IBD in 48% of patients, receipt of a solid organ transplant in 21%, a chronic medical condition and/or use of other immunosuppressive medication in 18%, cancer or its treatment in 9%, and HIV/AIDS in 3%.

The C. difficile infection was recurrent in 54% of cases, refractory in 12%, and severe or complicated in 34%.

The large majority of the patients (78%) underwent their FMT procedure in the outpatient setting. On average, the mean follow-up was 12 months (range, 3-51 months).

The results showed that 52 patients did not have any recurrence of C. difficile infection within 12 weeks of FMT, reported Dr. Ihunnah. Nine of the patients who had a recurrence underwent a second FMT, and seven of them did not have any additional recurrences. The final cure rate was therefore 89%.

Overall, nine patients (14%) had a serious adverse event within 12 weeks of their FMT: There were seven unplanned hospitalizations (most commonly due to a flare of IBD) and two deaths (one due to worsening of preexisting pneumonia unrelated to FMT and the one due to aspiration).

Nonserious adverse events included two cases of self-limited diarrhea in which no pathogen was identified, four cases of mild abdominal discomfort, one case of minor mucosal tear, and two cases of colectomy among patients with ulcerative colitis performed more than 100 days after FMT.

Dr. Ihunnah and Dr. Kelly disclosed no relevant conflicts of interest.

SAN DIEGO – Fecal microbiota transplantation is effective and safe for treating Clostridium difficile infection in immunocompromised patients, according to a retrospective study of 66 patients treated in the United States and Canada.

The final cure rate after one or two fecal microbiota transplantation (FMT) procedures was 89%, first author Dr. Chioma Ihunnah reported at the annual meeting of the American College of Gastroenterology.

There were no infectious complications, but about 10% of patients with inflammatory bowel disease (IBD) had a flare. One patient with severe C. difficile infection died as a result of aspiration during the procedure, but there were no deaths directly related to the fecal microbiota.

"This series demonstrates the effective use of fecal microbiota transplantation for C. diff infection in immunocompromised patients. The rate of cure observed in this study is similar to rates observed in similar studies of immunocompetent patients," said Dr. Ihunnah, a second-year resident in internal medicine at Brown University in Providence, R.I.

"Prospective studies of FMT in immunocompromised patients are needed to confirm efficacy and safety in this population. Additionally, the creation of a national registry for monitoring short- and long-term adverse events after FMT would better provide understanding of patient characteristics that may ultimately correlate with safety and efficacy of FMT," she added.

Session attendee Dr. Samir Shah, also of Brown University, said, "I am curious. There are no guidelines for what we do with our IBD patients with C. diff as far as their medicine. Did you have any protocols to continue medicines or stop medicines, or was it center specific?"

Continuation of antibiotics appeared largely center specific, although analyses are still ongoing, Dr. Ihunnah replied. "The IBD-specific medications were continued, to our knowledge. It was limited to what [data] the centers sent us, but to our knowledge, they were all continued."

In a related press briefing, Dr. Colleen R. Kelly, a study coauthor and a clinical assistant professor at Brown, said that although FMT generally appears to be safe, there have been concerns that complications are underreported.

"We focused on immunocompromised patients because our feeling was that if anybody was going to have a problem with getting an infection or another problem from FMT, that it would be this particular group of patients," she explained, as feces are rich in microorganisms. "There were some worries that some of these very severely immunocompromised patients could get sepsis or could get very ill. And that doesn’t seem to be the case."

The patient who died had a severe C. difficile infection and experienced aspiration during sedation for FMT via colonoscopy. "It maybe brings up the idea that in sicker patients, to just carefully look at the route of administration that you choose to administer FMT and use the least invasive, safest route possible," she said.

The future appears bright for improvements in FMT, such as delivery by pill and tailoring of the material administered, according to Dr. Kelly.

"We won’t be using whole stool a few years from now," she predicted. "There are people who are looking very hard at finding what is the active ingredient, what are the key species, one or more bacteria, that we need to restore this diversity to the flora ... There are companies working on it right now, and with this kind of evidence behind it, to develop a pill that could potentially be used to treat millions of people rather than the 130 people I’ve been able to treat over the last 5 years by conventional means. I really look forward to all of these blends and formulations that are coming around the corner."

Press briefing moderator Dr. Michael E. Cox, of Mercy Medical Center in Baltimore, noted that his center has experienced some failures of FMT that appeared to occur when patients resumed antibiotic therapy. "Do you counsel your patients not to go on antibiotics for a set period of time?" he asked.

Patients receive a lot of counseling tailored at reducing inappropriate use of antibiotics and, when antibiotics are absolutely needed, those that are less likely to trigger a recurrence are selected, Dr. Kelly said. But recurrences of C. difficile infection have been rare in their experience. "I do have them take probiotics during future courses of antibiotics. There is a little bit of data that that can be protective," she noted.

Dr. Kelly cautioned against rushing to use FMT to treat conditions such as IBD, irritable bowel syndrome, and autism. "There are all these diseases where there is thought to be intestinal dysbiosis, and there is this real hope that fecal transplant is going to cure it all. And I just really throw up a big caution that we are not there with any of these other conditions at this point. And to treat those conditions with fecal transplant outside of a clinical trial, really, I don’t think, is right," she maintained.

"That probably bears repeating," commented press briefing discussant Dr. Brian E. Lacy, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. "So if somebody came to you and said, right now, what do you think are the best indications for FMT, what would your answer be?"

"Recurrent C. difficile infection or refractory C. difficile infection – people who aren’t getting better on antibiotics," Dr. Kelly replied.

"Some would say severe C. difficile infection, but that’s another place where I’d probably say there is a yellow light of caution, because in my experience, we have treated very few patients with severe C. diff infection. They don’t appear to do as well," she continued. "They are also much more complicated; they are very sick, patients in the intensive care unit with toxic megacolon. The standard of care in these patients in 2013 is a surgical colectomy."

In the study, the investigators reviewed data collected from 16 centers performing FMT for recurrent, refractory, severe, or complicated C. difficile infection.

Analyses were restricted to immunocompromised patients who underwent the procedure and had at least 12 weeks of follow-up. Overall, 92% of the patients were adults, with a mean age of 53 years (range, 20-82 years). Sixty-two percent of the patients were men.

The reason for immunocompromise was use of immunosuppressive medications for IBD in 48% of patients, receipt of a solid organ transplant in 21%, a chronic medical condition and/or use of other immunosuppressive medication in 18%, cancer or its treatment in 9%, and HIV/AIDS in 3%.

The C. difficile infection was recurrent in 54% of cases, refractory in 12%, and severe or complicated in 34%.

The large majority of the patients (78%) underwent their FMT procedure in the outpatient setting. On average, the mean follow-up was 12 months (range, 3-51 months).

The results showed that 52 patients did not have any recurrence of C. difficile infection within 12 weeks of FMT, reported Dr. Ihunnah. Nine of the patients who had a recurrence underwent a second FMT, and seven of them did not have any additional recurrences. The final cure rate was therefore 89%.

Overall, nine patients (14%) had a serious adverse event within 12 weeks of their FMT: There were seven unplanned hospitalizations (most commonly due to a flare of IBD) and two deaths (one due to worsening of preexisting pneumonia unrelated to FMT and the one due to aspiration).

Nonserious adverse events included two cases of self-limited diarrhea in which no pathogen was identified, four cases of mild abdominal discomfort, one case of minor mucosal tear, and two cases of colectomy among patients with ulcerative colitis performed more than 100 days after FMT.

Dr. Ihunnah and Dr. Kelly disclosed no relevant conflicts of interest.