Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections

New oxazolidinones are in clinical development for the treatment of tuberculosis and nontuberculous mycobacterial (NTM) infections, as a replacement for linezolid and tedizolid, which cause mitochondrial toxicity after prolonged treatment. Here, we carried out side-by-side measurements of mitochondr...

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Autores principales: Negatu, Dereje A., Aragaw, Wassihun Wedajo, Cangialosi, Julianna, Dartois, Véronique, Dick, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Clinical Therapeutics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112060/
https://www.ncbi.nlm.nih.gov/pubmed/36920191
http://dx.doi.org/10.1128/aac.01655-22
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author Negatu, Dereje A.
Aragaw, Wassihun Wedajo
Cangialosi, Julianna
Dartois, Véronique
Dick, Thomas
author_facet Negatu, Dereje A.
Aragaw, Wassihun Wedajo
Cangialosi, Julianna
Dartois, Véronique
Dick, Thomas
author_sort Negatu, Dereje A.
collection PubMed
description New oxazolidinones are in clinical development for the treatment of tuberculosis and nontuberculous mycobacterial (NTM) infections, as a replacement for linezolid and tedizolid, which cause mitochondrial toxicity after prolonged treatment. Here, we carried out side-by-side measurements of mitochondrial protein synthesis inhibition and activity against clinically relevant mycobacterial pathogens of approved and novel oxazolidinones. We found a large range of selectivity indices suggesting TBI-223 and sutezolid as promising candidates against tuberculosis and NTM lung disease caused by Mycobacterium kansasii.
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spelling pubmed-101120602023-04-19 Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections Negatu, Dereje A. Aragaw, Wassihun Wedajo Cangialosi, Julianna Dartois, Véronique Dick, Thomas Antimicrob Agents Chemother Clinical Therapeutics New oxazolidinones are in clinical development for the treatment of tuberculosis and nontuberculous mycobacterial (NTM) infections, as a replacement for linezolid and tedizolid, which cause mitochondrial toxicity after prolonged treatment. Here, we carried out side-by-side measurements of mitochondrial protein synthesis inhibition and activity against clinically relevant mycobacterial pathogens of approved and novel oxazolidinones. We found a large range of selectivity indices suggesting TBI-223 and sutezolid as promising candidates against tuberculosis and NTM lung disease caused by Mycobacterium kansasii. American Society for Microbiology 2023-03-15 /pmc/articles/PMC10112060/ /pubmed/36920191 http://dx.doi.org/10.1128/aac.01655-22 Text en Copyright © 2023 Negatu et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Clinical Therapeutics
Negatu, Dereje A.
Aragaw, Wassihun Wedajo
Cangialosi, Julianna
Dartois, Véronique
Dick, Thomas
Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections
title Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections
title_full Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections
title_fullStr Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections
title_full_unstemmed Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections
title_short Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections
title_sort side-by-side profiling of oxazolidinones to estimate the therapeutic window against mycobacterial infections
topic Clinical Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112060/
https://www.ncbi.nlm.nih.gov/pubmed/36920191
http://dx.doi.org/10.1128/aac.01655-22
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