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30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection
BACKGROUND: Antimicrobial resistance (AMR) is a challenge in individuals at risk for recurrent Clostrioides difficile infection (rCDI). Recognizing that AMR bacteria colonize the intestinal microbiota, therapeutic approaches that decolonize the gut of AMR bacteria would be valuable. Herein, we asses...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776079/ http://dx.doi.org/10.1093/ofid/ofaa417.029 |
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author | Walsh, Dana Gonzalez, Carlos Shannon, Bill Blount, Ken |
author_facet | Walsh, Dana Gonzalez, Carlos Shannon, Bill Blount, Ken |
author_sort | Walsh, Dana |
collection | PubMed |
description | BACKGROUND: Antimicrobial resistance (AMR) is a challenge in individuals at risk for recurrent Clostrioides difficile infection (rCDI). Recognizing that AMR bacteria colonize the intestinal microbiota, therapeutic approaches that decolonize the gut of AMR bacteria would be valuable. Herein, we assessed the microbial resistome before and after treatment with RBX7455—a room temperature-stable, orally-administered investigational microbiota-based therapeutic—in a Phase 1 trial for reducing CDI recurrence. METHODS: This investigator-sponsored trial enrolled 30 rCDI patients in 3 open-label treatment groups (n=10 per group): 1) Four RBX7455 capsules BID for 4 days, 2) Four RBX7455 capsules BID for 2 days, 3) Two RBX7455 capsules BID for 2 days. RBX7455 administration began 48 hours after finishing CDI antibiotics. Participants were asked to submit stool samples at baseline, 1, 7, 28 and 56 days after treatment. These were extracted and sequenced using a shallow shotgun method. Relative taxonomic abundances at the class level and the presence of AMR genes were determined for 148 participant samples and 11 product samples using 90% K-mer sequence coverage based on the MEGARes database. RESULTS: Ninety percent of participants met the primary endpoint of no CDI recurrence through 8 weeks after treatment, and participant microbiome compositions became more similar to RBX7455 after treatment. The total AMR counts per participant decreased from before to after treatment (p< .05, mixed effects model), with the pattern of AMRs identified (resistome) becoming more like the RBX7455 resistome (Figure 1). Most notably, AMRs associated with multi-drug, fluoroquinolone, and betalactam resistance decreased from before to after treatment. There was no significant difference among the groups with respect to clinical response or changes in microbiome composition and AMR content. Figure 1 Average total and per-class AMR gene counts in participant samples before and after RBX7455 treatment. [Image: see text] CONCLUSION: In a Phase 1 trial of RBX7455 for rCDI, AMR gene content decreased after treatment. This underscores the potential of microbiota-based therapies for decolonizing AMR bacteria from the gut microbiota. Continued clinical evaluation of RBX7455 is underway. DISCLOSURES: Dana Walsh, PhD, Rebiotix Inc. (Employee) Carlos Gonzalez, MS, BioRankings, LLC (Employee) Bill Shannon, PhD MBA, BioRankings, LLC (Employee) Ken Blount, PhD, Rebiotix Inc. (Employee) |
format | Online Article Text |
id | pubmed-7776079 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77760792021-01-07 30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection Walsh, Dana Gonzalez, Carlos Shannon, Bill Blount, Ken Open Forum Infect Dis Oral Abstracts BACKGROUND: Antimicrobial resistance (AMR) is a challenge in individuals at risk for recurrent Clostrioides difficile infection (rCDI). Recognizing that AMR bacteria colonize the intestinal microbiota, therapeutic approaches that decolonize the gut of AMR bacteria would be valuable. Herein, we assessed the microbial resistome before and after treatment with RBX7455—a room temperature-stable, orally-administered investigational microbiota-based therapeutic—in a Phase 1 trial for reducing CDI recurrence. METHODS: This investigator-sponsored trial enrolled 30 rCDI patients in 3 open-label treatment groups (n=10 per group): 1) Four RBX7455 capsules BID for 4 days, 2) Four RBX7455 capsules BID for 2 days, 3) Two RBX7455 capsules BID for 2 days. RBX7455 administration began 48 hours after finishing CDI antibiotics. Participants were asked to submit stool samples at baseline, 1, 7, 28 and 56 days after treatment. These were extracted and sequenced using a shallow shotgun method. Relative taxonomic abundances at the class level and the presence of AMR genes were determined for 148 participant samples and 11 product samples using 90% K-mer sequence coverage based on the MEGARes database. RESULTS: Ninety percent of participants met the primary endpoint of no CDI recurrence through 8 weeks after treatment, and participant microbiome compositions became more similar to RBX7455 after treatment. The total AMR counts per participant decreased from before to after treatment (p< .05, mixed effects model), with the pattern of AMRs identified (resistome) becoming more like the RBX7455 resistome (Figure 1). Most notably, AMRs associated with multi-drug, fluoroquinolone, and betalactam resistance decreased from before to after treatment. There was no significant difference among the groups with respect to clinical response or changes in microbiome composition and AMR content. Figure 1 Average total and per-class AMR gene counts in participant samples before and after RBX7455 treatment. [Image: see text] CONCLUSION: In a Phase 1 trial of RBX7455 for rCDI, AMR gene content decreased after treatment. This underscores the potential of microbiota-based therapies for decolonizing AMR bacteria from the gut microbiota. Continued clinical evaluation of RBX7455 is underway. DISCLOSURES: Dana Walsh, PhD, Rebiotix Inc. (Employee) Carlos Gonzalez, MS, BioRankings, LLC (Employee) Bill Shannon, PhD MBA, BioRankings, LLC (Employee) Ken Blount, PhD, Rebiotix Inc. (Employee) Oxford University Press 2020-12-31 /pmc/articles/PMC7776079/ http://dx.doi.org/10.1093/ofid/ofaa417.029 Text en © The Author 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Oral Abstracts Walsh, Dana Gonzalez, Carlos Shannon, Bill Blount, Ken 30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection |
title | 30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection |
title_full | 30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection |
title_fullStr | 30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection |
title_full_unstemmed | 30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection |
title_short | 30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection |
title_sort | 30. antimicrobial resistance genes are reduced following administration of investigational microbiota-based therapeutic rbx7455 to individuals with recurrent clostrioides difficile infection |
topic | Oral Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776079/ http://dx.doi.org/10.1093/ofid/ofaa417.029 |
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