By Will Boggs MD
NEW YORK (Reuters Health) - 16/1/2019
Fecal-microbiota transplantation (FMT) is superior to 10 days of fidaxomicin or vancomycin for resolving recurrent Clostridium difficile infection (CDI), according to results from a randomized open-label clinical trial.
"Any patient with recurrence of C. diff. should be considered for FMT," Dr. Christian Lodberg Hvas from Aarhus University Hospital, in Denmark told Reuters Health by email. "Some think that long-term vancomycin is the better choice, particularly in the multimorbid patient. We now know that this is not true."
Numerous studies have shown FMT to be superior to vancomycin for treating recurrent CDI, but FMT has not been compared with recently developed, oral, non-absorbable antibiotics like fidaxomicin.
Dr. Hvas' team compared the effects of FMT, fidaxomicin and standard-dose vancomycin in 64 patients with recurrent CDI: 24 were randomized to FMT preceded by four to 10 days of vancomycin 125 mg QID, 24 were randomized to 10 days of fidaxomicin 200 mg BID and 16 were randomized to 10 days of vancomycin 125 mg QID (standard treatment).
Combined clinical resolution and a negative C. difficile test, the primary outcome, were achieved by 17 (71%) FMT patients, eight (33%) fidaxomicin patients, and three (19%) vancomycin patients, with FMT statistically superior to fidaxomicin and vancomycin, the researchers report in Gastroenterology, online January 2.
Clinical resolution rates were also significantly higher with FMT (22/24, 92%) than with fidaxomicin (10/24, 42%) or vancomycin (3/16, 19%).
Overall, 24 patients experienced relapse following their allocated treatment and underwent rescue FMT. Eight weeks later, 20 (83%) of these patients had clinical resolution and a negative C. difficile test.
Among the 56 patients who failed screening, 49 underwent off-protocol FMT, and 39 (80%) of these had clinical resolution and a negative C. difficile test eight weeks later.
Overall, 11 of the 95 patients who had FMT had CDI recurrence at or before week eight. Hemoglobin was the only significant independent predictor of FMT failure, and the presence of anemia was associated with a 6.3-fold increased risk of FMT failure.
During eight weeks of follow-up, there was no difference between the three treatment groups in frequency of adverse events or serious adverse events, with the exception of CDI recurrence, and there were no deaths.
"Recurrent CDI may be life-threatening," Dr. Hvas said. "In patients who are ill and have recurrence, I think FMT should be considered first choice. This also applies to those in intensive care, in nursing homes, and those who are disabled by their disease. Before, we considered some patients 'too sick for FMT.' Now, we know that the sicker the patient, the stronger the argument for FMT."
Dr. Berhanu M. Geme from St. Luke's University Health Network, in Bethlehem, Pennsylvania, who studies FMT and was not involved in the new work, told Reuters Health by email, "FMT is a highly effective and readily available treatment for recurrent CDI. In fact, effectiveness of FMT is better than oral vancomycin. Most of our patient start feeling better the first week after FMT."
Dr. Horace R. D. Williams from Imperial College London, in the UK, who served on the joint British Society of Gastroenterology and Healthcare Infection Society working group that developed guidelines for the use of FMT for recurrent or refractory CDI, told Reuters Health by email, "Based on primary outcome alone, many would raise the question whether FMT should be the first port-of-call for all recurrent CDI (not CDI per se). However, FMT has a number of drawbacks, including its unpalatability, the potential need for invasive administration, the theoretical risk of transmission of infection, and the complex regulation associated with its use."
"Furthermore, this study only included patients with extremely stubborn recurrent CDI, who had failed vancomycin and other therapies up to seven times before in some cases - so this is a selective and extreme population," he said. "As such, this study certainly should not be seen as dismissive of the important role of pharmacotherapy in the treatment of recurrent CDI."
"It may be appropriate to consider FMT earlier in the pathway of treatment for patients with recurrent CDI than is currently the case (which is typically after a least two recurrences)," Dr. Williams said. "However, it should be recognized that vancomycin and fidaxomicin both still have an important role in the treatment of recurrent CDI."
SOURCE: https://bit.ly/2HegtzH Gastroenterology 2019.