Fresh versus frozen fecal microbiota transplantation

Last Updated: 2016-01-12

By Will Boggs MD

NEW YORK (Reuters Health) - Fresh and frozen fecal microbiota transplantation (FMT) offer similar efficacy for patients with recurrent Clostridium difficile infection (CDI), according to results of a randomized, double-blind, noninferiority trial.

"Given that frozen has similar efficacy to fresh FMT, FMT may be accessible to wider facilities and assist more patients," Dr. Christine H. Lee, from St. Joseph's Healthcare-Hamilton, Hamilton, Ontario, Canada, told Reuters Health by email.

Frozen-and-thawed FMT offers several advantages over fresh FMT, including lower cost due to reduced number and frequency of donor screenings, immediate availability, and the possibility of delivering FMT at centers that do not have on-site laboratory facilities.

Dr. Lee's team from six academic medical centers in Canada evaluated the safety and effectiveness of fresh versus frozen FMT in their noninferiority study of 232 patients with recurrent CDI.

Primary clinical resolution rates were similar in the frozen FMT (83.5%) and fresh FMT (85.1%) groups (p=0.01), and frozen FMT was deemed noninferior to fresh FMT, according to the January 12 JAMA report.

Results were similar in the modified intention-to-treat analysis of patients who received at least one FMT but required antibiotic for CDI between the FMTs or who received a type of FMT different from the first FMT, who were lost to follow-up, or who required systemic antibiotic therapy for other infections.

The most common adverse events considered at least possibly related to FMT included transient diarrhea (70%), abdominal cramps (10%), and nausea (<5%) during the 24 hours after FMT and constipation (20%), and excess flatulence (25%) during follow-up. The rates did not differ between FMT groups.

"There were no real surprises in the results given that anaerobic bacteria survive well frozen," Dr. Lee said. "Based on our experience of using both fresh and frozen in over 500 patients with CDI, I don't think there is any advantage to switching from one to another for an individual patient."

"Ongoing research is needed to capture the long-term safety and potential benefits of FMT and we are following FMT patients up to 10 years," she added.

Dr. Preeti N. Malani, from the University of Michigan Health System, Ann Arbor, who coauthored the editorial related to this report, told Reuters Health by email, "Our message to clinicians is that the evidence continues to grow in regards to FMT for recurrent CDI being safe and effective, and that they should not have qualms about using frozen stool, which can be considerably more convenient. In fact, using frozen stool should help provide access to FMT for more patients."

"I'd like to remind clinicians and patients that FMT has not been rigorously studied for indications other than recurrent CDI," she said. "We still do not yet know the long-term consequences, if any. We are just beginning to understand the microbiome -- lots more to learn in coming years."

Dr. Justin MacDonald from Cumming School of Medicine, University of Calgary, Alberta, Canada, who recently reviewed gastrointestinal dysbiosis and the use of fecal microbial transplantation in C difficile infection (http://bit.ly/1W3OgrV), told Reuters Health by email, "FMT is an emergent therapeutic with reasonable potential to address recurrent CDI -- however, there are many potential risks that remain undefined. As the authors of the study indicate, potential risks should be weighed against the significant morbidity and mortality associated with recurrent CDI."

"Other studies have also demonstrated the effectiveness of frozen FMT by oral capsule," he said.

Dr. Samuel P. Costello from Queen Elizabeth Hospital, Woodville, South Australia, has discussed the development of a frozen stool bank of screened donor stool to be used in this setting. He told Reuters Health by email, "This large randomized study confirms what previous smaller case series had suggested: that frozen stool is as effective as fresh stool for the treatment of recurrent CDI."

"Donor recruitment and testing is labor intensive and costly and by using a frozen stool bank with anonymous volunteers, the process becomes more economical," he explained. "Also frozen stool is available on demand and without delay. Also many donors of fresh stool are known to the recipient, and there are ethical as well as confidentiality concerns in screening known donors in the event that disease is found in a donor or transmitted to the recipient."

Several organizations funded this research. Four coauthors reported disclosures. The Claude D. Pepper Older Americans Independence Center partially supported the editorial.

SOURCE: http://bit.ly/1KblPl3 and http://bit.ly/1N59IG1

JAMA 2016.