Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.

The antimicrobial resistance crisis has persisted despite broad attempts at intervention. It has been proposed that an important driver of resistance is selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. But to date, there has been limited quantitat...

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Autores principales:	Clare L Kinnear, Elsa Hansen, Valerie J Morley, Kevin C Tracy, Meghan Forstchen, Andrew F Read, Robert J Woods
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a5b2d64d14c340cb8fcba4fd5a1497de
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spelling	oai:doaj.org-article:a5b2d64d14c340cb8fcba4fd5a1497de2021-12-02T19:54:43ZDaptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.1544-91731545-788510.1371/journal.pbio.3000987https://doaj.org/article/a5b2d64d14c340cb8fcba4fd5a1497de2020-12-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3000987https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The antimicrobial resistance crisis has persisted despite broad attempts at intervention. It has been proposed that an important driver of resistance is selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. But to date, there has been limited quantitative measure of the mean and variance of resistance following antibiotic exposure. Here we focus on the important nosocomial pathogen Enterococcus faecium in a hospital system where resistance to daptomycin is evolving despite standard interventions. We hypothesized that the intravenous use of daptomycin generates off-target selection for resistance in transmissible gastrointestinal (carriage) populations of E. faecium. We performed a cohort study in which the daptomycin resistance of E. faecium isolated from rectal swabs from daptomycin-exposed patients was compared to a control group of patients exposed to linezolid, a drug with similar indications. In the daptomycin-exposed group, daptomycin resistance of E. faecium from the off-target population was on average 50% higher than resistance in the control group (n = 428 clones from 22 patients). There was also greater phenotypic diversity in daptomycin resistance within daptomycin-exposed patients. In patients where multiple samples over time were available, a wide variability in temporal dynamics were observed, from long-term maintenance of resistance to rapid return to sensitivity after daptomycin treatment stopped. Sequencing of isolates from a subset of patients supports the argument that selection occurs within patients. Our results demonstrate that off-target gastrointestinal populations rapidly respond to intravenous antibiotic exposure. Focusing on the off-target evolutionary dynamics may offer novel avenues to slow the spread of antibiotic resistance.Clare L KinnearElsa HansenValerie J MorleyKevin C TracyMeghan ForstchenAndrew F ReadRobert J WoodsPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 18, Iss 12, p e3000987 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Clare L Kinnear Elsa Hansen Valerie J Morley Kevin C Tracy Meghan Forstchen Andrew F Read Robert J Woods Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.
description	The antimicrobial resistance crisis has persisted despite broad attempts at intervention. It has been proposed that an important driver of resistance is selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. But to date, there has been limited quantitative measure of the mean and variance of resistance following antibiotic exposure. Here we focus on the important nosocomial pathogen Enterococcus faecium in a hospital system where resistance to daptomycin is evolving despite standard interventions. We hypothesized that the intravenous use of daptomycin generates off-target selection for resistance in transmissible gastrointestinal (carriage) populations of E. faecium. We performed a cohort study in which the daptomycin resistance of E. faecium isolated from rectal swabs from daptomycin-exposed patients was compared to a control group of patients exposed to linezolid, a drug with similar indications. In the daptomycin-exposed group, daptomycin resistance of E. faecium from the off-target population was on average 50% higher than resistance in the control group (n = 428 clones from 22 patients). There was also greater phenotypic diversity in daptomycin resistance within daptomycin-exposed patients. In patients where multiple samples over time were available, a wide variability in temporal dynamics were observed, from long-term maintenance of resistance to rapid return to sensitivity after daptomycin treatment stopped. Sequencing of isolates from a subset of patients supports the argument that selection occurs within patients. Our results demonstrate that off-target gastrointestinal populations rapidly respond to intravenous antibiotic exposure. Focusing on the off-target evolutionary dynamics may offer novel avenues to slow the spread of antibiotic resistance.
format	article
author	Clare L Kinnear Elsa Hansen Valerie J Morley Kevin C Tracy Meghan Forstchen Andrew F Read Robert J Woods
author_facet	Clare L Kinnear Elsa Hansen Valerie J Morley Kevin C Tracy Meghan Forstchen Andrew F Read Robert J Woods
author_sort	Clare L Kinnear
title	Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.
title_short	Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.
title_full	Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.
title_fullStr	Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.
title_full_unstemmed	Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.
title_sort	daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant enterococcus faecium.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/a5b2d64d14c340cb8fcba4fd5a1497de
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Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium.

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