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Sequential antibiotic therapy in the laboratory and in the patient

Laboratory experiments suggest that rapid cycling of antibiotics during the course of treatment could successfully counter resistance evolution. Drugs involving collateral sensitivity could be particularly suitable for such therapies. However, the environmental conditions in vivo differ from those i...

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Autores principales: Nyhoegen, Christin, Uecker, Hildegard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9810433/
https://www.ncbi.nlm.nih.gov/pubmed/36596451
http://dx.doi.org/10.1098/rsif.2022.0793
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author Nyhoegen, Christin
Uecker, Hildegard
author_facet Nyhoegen, Christin
Uecker, Hildegard
author_sort Nyhoegen, Christin
collection PubMed
description Laboratory experiments suggest that rapid cycling of antibiotics during the course of treatment could successfully counter resistance evolution. Drugs involving collateral sensitivity could be particularly suitable for such therapies. However, the environmental conditions in vivo differ from those in vitro. One key difference is that drugs can be switched abruptly in the laboratory, while in the patient, pharmacokinetic processes lead to changing antibiotic concentrations including periods of dose overlaps from consecutive administrations. During such overlap phases, drug–drug interactions may affect the evolutionary dynamics. To address the gap between the laboratory and potential clinical applications, we set up two models for comparison—a ‘laboratory model’ and a pharmacokinetic-pharmacodynamic ‘patient model’. The analysis shows that in the laboratory, the most rapid cycling suppresses the bacterial population always at least as well as other regimens. For patient treatment, however, a little slower cycling can sometimes be preferable if the pharmacodynamic curve is steep or if drugs interact antagonistically. When resistance is absent prior to treatment, collateral sensitivity brings no substantial benefit unless the cell division rate is low and drug cycling slow. By contrast, drug–drug interactions strongly influence the treatment efficiency of rapid regimens, demonstrating their importance for the optimal choice of drug pairs.
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spelling pubmed-98104332023-01-11 Sequential antibiotic therapy in the laboratory and in the patient Nyhoegen, Christin Uecker, Hildegard J R Soc Interface Life Sciences–Mathematics interface Laboratory experiments suggest that rapid cycling of antibiotics during the course of treatment could successfully counter resistance evolution. Drugs involving collateral sensitivity could be particularly suitable for such therapies. However, the environmental conditions in vivo differ from those in vitro. One key difference is that drugs can be switched abruptly in the laboratory, while in the patient, pharmacokinetic processes lead to changing antibiotic concentrations including periods of dose overlaps from consecutive administrations. During such overlap phases, drug–drug interactions may affect the evolutionary dynamics. To address the gap between the laboratory and potential clinical applications, we set up two models for comparison—a ‘laboratory model’ and a pharmacokinetic-pharmacodynamic ‘patient model’. The analysis shows that in the laboratory, the most rapid cycling suppresses the bacterial population always at least as well as other regimens. For patient treatment, however, a little slower cycling can sometimes be preferable if the pharmacodynamic curve is steep or if drugs interact antagonistically. When resistance is absent prior to treatment, collateral sensitivity brings no substantial benefit unless the cell division rate is low and drug cycling slow. By contrast, drug–drug interactions strongly influence the treatment efficiency of rapid regimens, demonstrating their importance for the optimal choice of drug pairs. The Royal Society 2023-01-04 /pmc/articles/PMC9810433/ /pubmed/36596451 http://dx.doi.org/10.1098/rsif.2022.0793 Text en © 2023 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 Life Sciences–Mathematics interface
Nyhoegen, Christin
Uecker, Hildegard
Sequential antibiotic therapy in the laboratory and in the patient
title Sequential antibiotic therapy in the laboratory and in the patient
title_full Sequential antibiotic therapy in the laboratory and in the patient
title_fullStr Sequential antibiotic therapy in the laboratory and in the patient
title_full_unstemmed Sequential antibiotic therapy in the laboratory and in the patient
title_short Sequential antibiotic therapy in the laboratory and in the patient
title_sort sequential antibiotic therapy in the laboratory and in the patient
topic Life Sciences–Mathematics interface
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9810433/
https://www.ncbi.nlm.nih.gov/pubmed/36596451
http://dx.doi.org/10.1098/rsif.2022.0793
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