Cargando…
An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen
A key challenge in antibiotic stewardship is figuring out how to use antibiotics therapeutically without promoting the evolution of antibiotic resistance. Here, we demonstrate proof of concept for an adjunctive therapy that allows intravenous antibiotic treatment without driving the evolution and on...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707840/ https://www.ncbi.nlm.nih.gov/pubmed/33258450 http://dx.doi.org/10.7554/eLife.58147 |
_version_ | 1783617441541128192 |
---|---|
author | Morley, Valerie J Kinnear, Clare L Sim, Derek G Olson, Samantha N Jackson, Lindsey M Hansen, Elsa Usher, Grace A Showalter, Scott A Pai, Manjunath P Woods, Robert J Read, Andrew F |
author_facet | Morley, Valerie J Kinnear, Clare L Sim, Derek G Olson, Samantha N Jackson, Lindsey M Hansen, Elsa Usher, Grace A Showalter, Scott A Pai, Manjunath P Woods, Robert J Read, Andrew F |
author_sort | Morley, Valerie J |
collection | PubMed |
description | A key challenge in antibiotic stewardship is figuring out how to use antibiotics therapeutically without promoting the evolution of antibiotic resistance. Here, we demonstrate proof of concept for an adjunctive therapy that allows intravenous antibiotic treatment without driving the evolution and onward transmission of resistance. We repurposed the FDA-approved bile acid sequestrant cholestyramine, which we show binds the antibiotic daptomycin, as an ‘anti-antibiotic’ to disable systemically-administered daptomycin reaching the gut. We hypothesized that adjunctive cholestyramine could enable therapeutic daptomycin treatment in the bloodstream, while preventing transmissible resistance emergence in opportunistic pathogens colonizing the gastrointestinal tract. We tested this idea in a mouse model of Enterococcus faecium gastrointestinal tract colonization. In mice treated with daptomycin, adjunctive cholestyramine therapy reduced the fecal shedding of daptomycin-resistant E. faecium by up to 80-fold. These results provide proof of concept for an approach that could reduce the spread of antibiotic resistance for important hospital pathogens. |
format | Online Article Text |
id | pubmed-7707840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77078402020-12-02 An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen Morley, Valerie J Kinnear, Clare L Sim, Derek G Olson, Samantha N Jackson, Lindsey M Hansen, Elsa Usher, Grace A Showalter, Scott A Pai, Manjunath P Woods, Robert J Read, Andrew F eLife Evolutionary Biology A key challenge in antibiotic stewardship is figuring out how to use antibiotics therapeutically without promoting the evolution of antibiotic resistance. Here, we demonstrate proof of concept for an adjunctive therapy that allows intravenous antibiotic treatment without driving the evolution and onward transmission of resistance. We repurposed the FDA-approved bile acid sequestrant cholestyramine, which we show binds the antibiotic daptomycin, as an ‘anti-antibiotic’ to disable systemically-administered daptomycin reaching the gut. We hypothesized that adjunctive cholestyramine could enable therapeutic daptomycin treatment in the bloodstream, while preventing transmissible resistance emergence in opportunistic pathogens colonizing the gastrointestinal tract. We tested this idea in a mouse model of Enterococcus faecium gastrointestinal tract colonization. In mice treated with daptomycin, adjunctive cholestyramine therapy reduced the fecal shedding of daptomycin-resistant E. faecium by up to 80-fold. These results provide proof of concept for an approach that could reduce the spread of antibiotic resistance for important hospital pathogens. eLife Sciences Publications, Ltd 2020-12-01 /pmc/articles/PMC7707840/ /pubmed/33258450 http://dx.doi.org/10.7554/eLife.58147 Text en © 2020, Morley et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Evolutionary Biology Morley, Valerie J Kinnear, Clare L Sim, Derek G Olson, Samantha N Jackson, Lindsey M Hansen, Elsa Usher, Grace A Showalter, Scott A Pai, Manjunath P Woods, Robert J Read, Andrew F An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen |
title | An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen |
title_full | An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen |
title_fullStr | An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen |
title_full_unstemmed | An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen |
title_short | An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen |
title_sort | adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen |
topic | Evolutionary Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707840/ https://www.ncbi.nlm.nih.gov/pubmed/33258450 http://dx.doi.org/10.7554/eLife.58147 |
work_keys_str_mv | AT morleyvaleriej anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT kinnearclarel anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT simderekg anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT olsonsamanthan anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT jacksonlindseym anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT hansenelsa anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT ushergracea anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT showalterscotta anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT paimanjunathp anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT woodsrobertj anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT readandrewf anadjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT morleyvaleriej adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT kinnearclarel adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT simderekg adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT olsonsamanthan adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT jacksonlindseym adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT hansenelsa adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT ushergracea adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT showalterscotta adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT paimanjunathp adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT woodsrobertj adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen AT readandrewf adjunctivetherapyadministeredwithanantibioticpreventsenrichmentofantibioticresistantclonesofacolonizingopportunisticpathogen |