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The risk of drug resistance during long-acting antimicrobial therapy

The emergence of drug resistance during antimicrobial therapy is a major global health problem, especially for chronic infections like human immunodeficiency virus, hepatitis B and C, and tuberculosis. Sub-optimal adherence to long-term treatment is an important contributor to resistance risk. New l...

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Detalles Bibliográficos
Autores principales: Nande, Anjalika, Hill, Alison L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653236/
https://www.ncbi.nlm.nih.gov/pubmed/36350211
http://dx.doi.org/10.1098/rspb.2022.1444
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author Nande, Anjalika
Hill, Alison L.
author_facet Nande, Anjalika
Hill, Alison L.
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description The emergence of drug resistance during antimicrobial therapy is a major global health problem, especially for chronic infections like human immunodeficiency virus, hepatitis B and C, and tuberculosis. Sub-optimal adherence to long-term treatment is an important contributor to resistance risk. New long-acting drugs are being developed for weekly, monthly or less frequent dosing to improve adherence, but may lead to long-term exposure to intermediate drug levels. In this study, we analyse the effect of dosing frequency on the risk of resistance evolving during time-varying drug levels. We find that long-acting therapies can increase, decrease or have little effect on resistance, depending on the source (pre-existing or de novo) and degree of resistance, and rates of drug absorption and clearance. Long-acting therapies with rapid drug absorption, slow clearance and strong wild-type inhibition tend to reduce resistance caused by partially resistant strains in the early stages of treatment even if they do not improve adherence. However, if subpopulations of microbes persist and can reactivate during sub-optimal treatment, longer-acting therapies may substantially increase the resistance risk. Our results show that drug kinetics affect selection for resistance in a complicated manner, and that pathogen-specific models are needed to evaluate the benefits of new long-acting therapies.
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spelling pubmed-96532362022-11-22 The risk of drug resistance during long-acting antimicrobial therapy Nande, Anjalika Hill, Alison L. Proc Biol Sci Biological Applications The emergence of drug resistance during antimicrobial therapy is a major global health problem, especially for chronic infections like human immunodeficiency virus, hepatitis B and C, and tuberculosis. Sub-optimal adherence to long-term treatment is an important contributor to resistance risk. New long-acting drugs are being developed for weekly, monthly or less frequent dosing to improve adherence, but may lead to long-term exposure to intermediate drug levels. In this study, we analyse the effect of dosing frequency on the risk of resistance evolving during time-varying drug levels. We find that long-acting therapies can increase, decrease or have little effect on resistance, depending on the source (pre-existing or de novo) and degree of resistance, and rates of drug absorption and clearance. Long-acting therapies with rapid drug absorption, slow clearance and strong wild-type inhibition tend to reduce resistance caused by partially resistant strains in the early stages of treatment even if they do not improve adherence. However, if subpopulations of microbes persist and can reactivate during sub-optimal treatment, longer-acting therapies may substantially increase the resistance risk. Our results show that drug kinetics affect selection for resistance in a complicated manner, and that pathogen-specific models are needed to evaluate the benefits of new long-acting therapies. The Royal Society 2022-11-09 2022-11-09 /pmc/articles/PMC9653236/ /pubmed/36350211 http://dx.doi.org/10.1098/rspb.2022.1444 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Biological Applications
Nande, Anjalika
Hill, Alison L.
The risk of drug resistance during long-acting antimicrobial therapy
title The risk of drug resistance during long-acting antimicrobial therapy
title_full The risk of drug resistance during long-acting antimicrobial therapy
title_fullStr The risk of drug resistance during long-acting antimicrobial therapy
title_full_unstemmed The risk of drug resistance during long-acting antimicrobial therapy
title_short The risk of drug resistance during long-acting antimicrobial therapy
title_sort risk of drug resistance during long-acting antimicrobial therapy
topic Biological Applications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653236/
https://www.ncbi.nlm.nih.gov/pubmed/36350211
http://dx.doi.org/10.1098/rspb.2022.1444
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