Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1784828641985691648 |
---|---|
author | Nande, Anjalika Hill, Alison L. |
author_facet | Nande, Anjalika Hill, Alison L. |
author_sort | Nande, Anjalika |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9653236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT nandeanjalika theriskofdrugresistanceduringlongactingantimicrobialtherapy AT hillalisonl theriskofdrugresistanceduringlongactingantimicrobialtherapy AT nandeanjalika riskofdrugresistanceduringlongactingantimicrobialtherapy AT hillalisonl riskofdrugresistanceduringlongactingantimicrobialtherapy |