San Diego, CA (October 14, 2013) – Fecal microbiota transplantation (FMT) is effective in resolving Clostridium difficile infection (CDI) in immunocompromised patients with few serious adverse events according to an retrospective series presented at the 78th Annual Scientific Meeting of the American College of Gastroenterology. Two other studies looked at FMT in Inflammatory Bowel Disease (IBD) patients who also suffered from C. difficile infection, as well as the impact of altering gut flora with transplant of fecal bacteria upon symptoms of Irritable Bowel Syndrome.
FMT Effective in Immunocompromised Patients at Higher Risk for C. difficile Infection
According to Colleen R. Kelly, M.D., FACG of Brown University, one of the investigators involved in a multicenter retrospective study of fecal microbiota transplantation, patients who are immunocompromised are at increased risk of C. difficile infection, which has increased to epidemic proportions over the past decade.
“Fecal microbiota transplantation appears effective for the treatment of C. difficile infection, though there is concern that immunocompromised patients may be at increased risk of having adverse events related to FMT,” explained Dr. Kelly.
Investigators analyzed the use of FMT in immunocompromised patients whose C. difficile infection was recurrent, refractory, or severe. The cure rate among immunocompromised patients with C. difficile after a single fecal transplant was 78 percent, with 52 patients experiencing no recurrence at least 12 weeks post-FMT. Nine patients underwent repeat FMT, of which seven had no further C. difficile infection. The overall cure rate was 89 percent.
Cases included adult (61) and pediatric (5) patients treated with FMT for refractory, recurrent, and overlap of recurrent/refractory and severe C. difficile infection. Among the patients in the study, the mean follow-up period between fecal microbiota transplantation and data collection was 12 months. These patients had compromised immune systems because of HIV/AIDS, solid organ transplant, oncologic conditions, immunosuppressive therapy for IBD, or due to medical condition/ medication.
Fifteen percent of patients (n=10), had a serious adverse event within 12 weeks post-FMT, of which eight were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT. Three IBD patients (9 percent) experienced disease flare post-FMT. Two ulcerative colitis (UC) patients underwent colectomy related to course of UC within less than 100 days after FMT. One patient had a superficial mucosal tear caused by the FMT colonoscopy and four patients reported mild, self limited abdominal discomfort post-FMT.
“This series demonstrates effective use of fecal microbiota transplantation for C. difficile in immunocompromised patients with few serious adverse effects or related adverse effects,” concluded Dr. Kelly. Despite these few adverse events related to FMT, Dr. Kelly and her co-investigators found, importantly, that there were no infectious complications in these high-risk patients. Further prospective studies of FMT in immunocompromised patients are needed to confirm safety and efficacy in this population, noted Dr. Kelly.
Fecal Transplant Resolves C. Difficile in Patients with IBD, but IBD Symptoms Remain
Researchers from Mayo Clinic found that FMT in adults with C. difficile infection and Inflammatory Bowel Disease appears to be a safe and effective mode of treatment, and leads to resolution of C. difficile infection in most patients. However, fecal transplantation does not appear to improve the course of IBD in most patients, they observed in a small study of 13 patients.
Inflammatory bowel disease patients often get C. difficile infection, which is associated with poor outcomes. Lead author Sahil Khanna, M.D., who presented this study on behalf of his colleagues from Mayo Clinic, reports “the data is controversial regarding the utility of FMT for management of IBD.”
In the study, adult patients with IBD (Crohn’s disease or ulcerative colitis) and recurrent or non-resolving CDI who had failed oral treatment for CDI were enrolled in the FMT program. Patients in the study had experienced multiple episodes of CDI and had failed a median of 5 CDI therapy regimens, with 77 percent (n=10) failing two or more different drugs, and 77 percent (n=10) failing at least one prolonged vancomycin taper.
After treatment with FMT, 92 percent (n=12) noted some improvement in their symptoms and over all well-being, one had no improvement in diarrhea, tested positive for CDI, and was treated with fidaxomicin. Of the 12 with symptomatic improvement, six patients had complete resolution and six had partial improvement. Of these six with some residual diarrhea, five tested negative for CDI, and one was empirically treated with metronidazole at home without testing for CDI with no improvement.
Overall, 85 percent (n=11) of patients had resolution of CDI either by symptom resolution or by laboratory testing. The median time to resolution in patients with complete symptom resolution was 2 days with a range of 1 day to 14 days. No patient was able to decrease or discontinue IBD therapy after FMT. In fact, 46 percent needed escalation of their IBD therapy after clearance of CDI. There were no adverse events noted with FMT in these patients by the Mayo team.
Small Study of IBS Patients Suggests Symptom Improvement with Fecal Microbiota Transplant In a small study at Montefiore Medical Center in New York City, David M. Pinn, M.D. and colleagues, under the guidance of Lawrence J. Brandt, M.D., MACG followed up on patients treated with fecal microbiota transplantation (FMT) for refractory IBS after interventions of dietary modification, probiotics, antibiotics, and/or anti-depressants had failed.
FMT resolved or improved symptoms in 70 percent of the patients with refractory IBS, including abdominal pain (72 percent), bowel habit (69 percent), dyspepsia (67 percent), bloating (50 percent), and flatus (45 percent). FMT also resulted in improved quality of life (46 percent) as reported by the 13 patients who completed a questionnaire which assessed global well-being and collected other clinical data.
Thirteen patients (54 percent women) completed the study. The average age was 45 years (range: 23-75 years). Patients had IBS for an average of 73 months before FMT (range: 12-180 months). The average time from FMT to data collection was 11 months (range: 6 to 18 months). Before FMT, global well-being was reported as “good” in zero patients, “acceptable” in four patients (30 percent), and “poor” in nine patients (69 percent). After FMT, global well-being was “good” in three patients (23 percent), “acceptable” in six (46 percent) and “poor” in four (30 percent).
"IBS is a disease that has a tremendous effect on the quality of people’s lives and has proven to be very difficult to treat. In our study, we showed that fecal microbiota transplantation can be a safe and effective treatment modality for the symptomatic relief of refractory IBS. Of the participants in the study, 70 percent had symptomatic relief and nearly half reported an improvement in their overall well-being,” commented Dr. Pinn.
He added, “Our data was generated before the FDA regulations on FMT were put into effect and any further studies on this important area would have to be performed under an IND and with IRB approval. FMT is an evolving field in medicine, and, as this study demonstrates, it is proving to be an exciting, groundbreaking, new approach in the treatment of IBS."
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