Tag Archives: FMT treatment for recurrent CDI

Study Investigators Find Combination of Vancomycin and FMT Superior In Treating Recurrent C.difficile Infection (rCDI)

The combination of vancomycin and fecal microbiota transplantation was found to be superior to fidaxomicin or vancomycin in the treatment of patients with recurrent Clostridium difficile infection (rCDI), according to a study published in Gastroenterology.

This randomized, single-center trial was designed to compare the efficacy of fecal microbiota transplantation with that of fidaxomicin and vancomycin.

Sixty-four adults with recurrent CDI seen at a gastroenterology clinic in Denmark between April 5, 2016 and June 10, 2018 were randomly assigned to a group receiving fecal microbiota transplantation applied by colonoscopy or nasojejunal tube after 4 to 10 days of 125 mg vancomycin 4 times daily (n=24), or 10 days of 200 mg fidaxomicin 2 times daily (n=24), or 10 days of 125 mg vancomycin 4 times daily (n=16).

Patients experiencing a CDI recurrence after this course of treatment, and those who could not be randomly assigned were provided rescue fecal microbiota transplantation. The primary study outcome was combined clinical resolution and negative polymerase chain reaction test for C difficile toxin at 8 weeks post-treatment, and secondary end points included week 8 clinical resolution.

The combination of negative C difficile test results and clinical resolution was observed in 71% of the 24 participants who received fecal microbiota transplantation (95% CI, 49-87%; n=17), 33% of the 24 participants who received fidaxomicin (95% CI, 16-55%; n=8), and 19% of the 16 participants (95% CI, 5-46%; n=3) who received vancomycin (fecal microbiota transplantation vs fidaxomicinP=.009; fecal microbiota transplantation vs vancomycin, P=.001; fidaxomicin vs vancomycin, P=.31). Clinical resolution was observed in 92% of participants who received fecal microbiota transplantation (n=22; P=.0002), 42% of participants who were treated with fidaxomicin (n=10; <.0001), and 19% of participants who were treated with vancomycin (n=3; P=.13). No significant differences in results were seen between patients receiving initial fecal microbiota transplantation therapy and those who received rescue treatment with such a transplant.

Of note, adverse events (transient abdominal pain, constipation, bloating and diarrhea) were observed in 10 of the participants who received a fecal microbiota transplant, 1 of which was classified as severe.

Researchers noted limitation of a lack of patients with C difficile ribotype 027, such that results may not be generalizable to settings with a high ribotype 027 frequency. Study interventions were also unblinded, introducing the possibility of observer bias, although the C difficile toxin test was applied to all patients at all time points in an effort to obtain objective outcome measures.

Study investigators concluded, “[fecal microbiota transplantation] was superior to both fidaxomicin and vancomycin monotherapies for [recurrent] CDI, with regard to both combined clinical and microbiological resolution and clinical resolution alone.”

Reference

https://www.infectiousdiseaseadvisor.com/respiratory/new-powder-formulation-tuberculosis-vaccine-candidate-is-in-human-trial/article/829508/

Hvas CL, Jørgensen SMD, Jørgensen SP, et al. Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent Clostridium difficile infection [published online January 2, 2019]. Gastroenterology. doi: 10.1053/j.gastro.2018.12.019

Researchers Utilize Deep Metagenomic Sequencing to Profile FMT ‘s Retracting the Gut Microbiome Features That Coincided With Successful Fecal Transplant Engraftment

A team led by investigators at the Broad Institute have started untangling the bacterial strains that influence successful fecal microbiota transplantation (FMT) engraftment in individuals treated for recurrent Clostridium difficile infection.

As they reported in Cell Host & Microbe today, researchers from the Broad Institute, Massachusetts Institute of Technology, Massachusetts General Hospital, and elsewhere used deep metagenomic sequencing to profile FMT in four FMT donors and 19 recipients with C. difficile infections, retracing the gut microbiome features that coincided with successful fecal transplant engraftment.

The initial gut microbial communities in both the donors and the recipients seemed to influence this process, the team noted, particularly bacterial abundance and strain phylogeny. The final gut microbe composition differed between donors and post-FMT recipients, though, with specific strains that originated in the host either taking hold or falling by the wayside in recipients in an “all-or-nothing” manner.

“This paper provides a context for understanding how to make these live biological therapeutics as an alternative to transferring raw fecal matter,” co-senior author Eric Alm, co-director of MIT’s Center for Microbiome Informatics and Therapeutics, said in a statement.

“We describe a model focused on three elements, including bacterial engraftment, growth, and mechanism of action, that need to be considered when developing these live therapies targeting the gut microorganisms, or microbiome,” added Alm, who is also affiliated with the Broad Institute and Finch Therapeutics.

Along with its use for treating recurrent C. difficile infection, the team noted that FMT has been proposed in other conditions such as inflammatory bowel disease and metabolic syndrome. Even so, there is a ways to go in understanding the factors influencing bacterial engraftment and effectiveness in the recipient gut — information needed to move the approach from a shotgun approach using fecal donor material to microbe-based treatments based on purified collections of specific bacteria.

“Although the success of FMT requires donor bacteria to engraft in the patient’s gut, the forces governing engraftment in humans are unknown,” the authors wrote.

To follow this process, the researchers used the Illumina GAIIx instrument to do deep metagenomic sequencing on seven stool samples from four healthy donors and 67 samples collected over time from 19 individuals treated for C. difficile infection with FMT.

With the help of statistical modeling and a new computational method dubbed Strain Finder, the team looked at the bacterial species that successfully engrafted in FMT recipients and followed strain genotypes over time. It also mapped the metagenomes to Human Microbiome Project reference genomes to take a look at bacterial taxa abundance.

Prior to treatment, for example, FMT recipients had lower-than-usual gut microbiome diversity. And while gut microbial community patterns shifted in recipients after FMT, the resulting gut microbiomes continued to differ from the original donor microbiomes, the researchers reported.

Even so, their analytical methods made it possible predict post-FMR metagenomic operational taxa unit abundance and incidence.

With nearly 1,100 bacterial strains in the 79 samples considered, the team traced transmission of certain strains from FMT donors to recipients, noting that bacterial strains tended to engraft in an “all-or-nothing” manner, “whereby no strains or complete sets of strains colonize the patients.”

“We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient,” Alm and co-authors wrote. “Furthermore, donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonize patients receiving FMT.”

Such patterns were supported by the researchers’ follow-up analyses on 16S ribosomal RNA sequence data for stool samples from 10 more FMT donors and 18 recipients, as well as an analysis of metagenomic sequence data for samples from five individuals treated with FMT for metabolic syndrome.

“Together,” they authors said, “these findings suggest that the principles of engraftment we discovered for recurrent C. difficile infection may generalize to other disease indications, including metabolic syndrome.”

 

To read article in its entirety please click on the following link to be redirected:

https://www.genomeweb.com/sequencing/donor-recipient-strain-analyses-offer-fecal-transplant-engraftment-clues