Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization with a Metagenomic Perspective

Haggai Bar-Yoseph*, Shaqed Carasso, Shlomit Shklar, Alexander Korytny, Razi Even Dar, Haneen Daoud, Roni Nassar, Nitsan Maharshak, Khetam Hussein, Yuval Geffen, Yehuda Chowers, Naama Geva-Zatorsky, Mical Paul

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses. Methods: In this prospective cohort study, all consenting eligible CPE carriers received oral capsulized FMT for 2 days. Primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by polymerase chain reaction. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed. Results: Fifteen CPE carriers received FMT, 13 of whom completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants who achieved CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes. Conclusions: Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication. Clinical Trials Registration: NCT03167398.

Original languageEnglish
Pages (from-to)E166-E175
JournalClinical Infectious Diseases
Volume73
Issue number1
DOIs
StatePublished - 1 Jul 2021
Externally publishedYes

Funding

FundersFunder number
J&J Women in Science, Technology, Engineering, Math, Manufacturing and Design scholar
RHCC
Technion Integrated Cancer Center
Johnson and Johnson1015773
Canadian Institute for Advanced Research
Human Frontier Science ProgramCDA00025/2019-C
Israel Science Foundation1571/17, FL-000969
Ministry of Science and Technology, Israel3-14834
Technion-Israel Institute of Technology

    Keywords

    • carbapenemase-producing Enterobacteriaceae
    • carriers
    • multidrug-resistant bacteria
    • oral capsulized fecal microbiota transplantation
    • resistome

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