FMT Tied to Health Improvements Beyond Infection Clearance – MedPage Today

Apart from infection clearance, fecal microbiota transplant (FMT) was associated with a range of positive health outcomes in severely compromised patients with multidrug-resistant infections, preliminary results from a small U.K. pilot study suggested.

The open-label study of 20 patients infected during repeated hospitalizations was presented in an online press program organized by Digestive Disease Week (DDW), which was to have started this weekend but was cancelled because of the COVID-19 pandemic.

The study found FMT to be associated with:

Although only seven of the 17 patients who completed the full follow-up experienced decolonization of resistant bacteria by 6 months post-FMT, eight were able to undergo stem cell transplantation within 6 months and others were able to return to work.

"Many of these patients have had recurrent, prolonged courses of heavy-duty antibiotics, end-of-the-line treatments with high toxicity profiles, and repeated hospital stays," noted Benjamin H. Mullish, MD, of Imperial College London, in a DDW press release. "They had given up work or had family members forced to give up work to care for them -- having a huge impact on quality of life. After this experimental treatment, we saw many in this group being able to go back to work, play with their grandkids, and have an overall much better quality of life."

Last year, researchers in Italy reported that patients with Clostridioides difficile infection given FMT had a lower risk of bloodstream infection, fewer days of hospitalization, and a higher increase in overall survival compared with those treated with antibiotics.

Study Details

The 20 patients had intestinal colonization with multidrug-resistant organisms (MDROs), defined as carbapenemase-producing Enterobacteriaceae (such as Escherichia coli), vancomycin-resistant enterococci, or extended-spectrum beta-lactamase Enterobacteriaceae (ESBL).

Cases included patients with hematologic malignancies whose stem cell transplants were on hold because of fear of sepsis, and kidney transplant patients with urinary and bloodstream infections from MDROs. These patients received FMT as a fecal slurry delivered via nasogastric tube, and were then followed for 6 months with the clinical course compared with 6 months before FMT.

Nine treated patients had a background of recurrent ESBL urinary tract infections, and there was a reduction in these in the 6 months post-FMT compared with 6 months pre-treatment -- 42 episodes pre-FMT versus 12 post-FMT (P=0.008).

Of 11 patients with underlying chronic hematologic disease, eight were able to have stem cell transplants within 6 months of FMT.

In addition, during the 6 months post-FMT, patients had a shorter than usual hospital stay (P=0.002 for hematology patients, P=0.0002) for all patients) and fewer days on carbapenems (P=0.0017 for hematology patients, P=0.0005 for all patients).

Across all cases post-FMT, bloodstream infections were reduced, both for MDROs specifically (P=0.047) and for total bloodstream infections (P=0.028), and no serious FMT-related adverse events occurred, the researchers reported.

"These data led us to conclude that the restoration of colonization resistance occurring in association with FMT may not be by decolonization of a pathobiont alone, but could potentially represent other microbiota-mediated mechanisms too," the team stated. "Future studies should explore the impact of FMT for MDROs upon gut barrier function and/or changes in immune programming."

Presenter Julian Marchesi, PhD, also of Imperial College London, said during the briefing that the results suggest that FMT is safe to use in high-risk patients who are immunocompromised and that the benefits may extend beyond decolonization of MDROs to other microbiota-related outcomes. Marchesi added that the team had planned to roll out the FMT program to a larger number of patients across the U.K., but the COVID-19 pandemic necessitated putting that on hold.

"We have a strong foundation to take this to clinical trials," he said, adding that compared with similar patients who did not have FMT, FMT-treated stem-cell patients had much improved outcomes: "We saw them walking out the door in a couple of days in really good shape. We think that by bolstering their microbiome we're also doing something to their immune system."

Asked for her perspective, Yamini Natarajan, MD, of Baylor College of Medicine in Houston, who was not involved with the research, told MedPage Today: "It is encouraging to see these findings and lack of adverse events in this small pilot study. While the results are promising, further study is needed. These findings will need to be replicated in randomized, controlled trials before broad recommendations can be made."

Also commenting, Purna Kashyap, MBBS, of the Mayo Clinic in Rochester, Minnesota, who was also not involved with the study, pointed to several limitations, including the small size, lack of a control group, and absence of information on the donors, the power calculation, or primary and secondary outcomes. "I would be hesitant to draw any conclusions other than that [the approach] needs to be studied in a blinded randomized controlled study," he told MedPage Today. "Some of the parameters described, such as hospitalizations before and after FMT, can be driven by so many factors, and in this case using the patient as the control is not really appropriate."

The researchers also called the absence of a control group a major limitation.

DDW data are scheduled to be published in the May online supplements to Gastroenterology and GIE: Gastrointestinal Endoscopy.

Disclosures

The research was funded by the National Institute for Health Research, via the Imperial College Biomedical Research Centre, and the Medical Research Council; the authors disclosed no competing interests.

Natarajan reported no conflicts of interest in relation to her comments.

Kashyap reported financial relationships with Otsuka Pharmaceuticals, IP Group, and Novome, also unrelated to her comments.

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FMT Tied to Health Improvements Beyond Infection Clearance - MedPage Today