New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon?

Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with severe adverse effects, including myelosuppression and mitochondrial toxicity. As such, it is imperative to identify novel alterna...

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Bibliographic Details
Published in:Pharmaceutics Vol. 16; no. 6; p. 818
Main Authors: Chen, Ricky Hao, Burke, Andrew, Cho, Jin-Gun, Alffenaar, Jan-Willem, Davies Forsman, Lina
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 17.06.2024
MDPI
Subjects:
Clinical trials
delpazolid
Drug dosages
Drug resistance
eperezolid
linezolid
Metabolism
Metabolites
Pharmacokinetics
Protein synthesis
Proteins
Review
sutezolid
tedizolid
Toxicity
Tuberculosis
tuberculosis treatment
United States > US
sutezolid
linezolid
TBI-223
contezolid
tuberculosis treatment
eperezolid
posizolid
delpazolid
tedizolid
radezolid
ISSN:1999-4923, 1999-4923
Online Access:Get full text
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Summary:Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with severe adverse effects, including myelosuppression and mitochondrial toxicity. As such, it is imperative to identify novel alternatives that are better tolerated but equally or more effective. Therefore, this review aims to identify and explore the novel alternative oxazolidinones to potentially replace linezolid in the management of TB. The keywords tuberculosis and oxazolidinones were searched in PubMed to identify eligible compounds. The individual drug compounds were then searched with the term tuberculosis to identify the relevant in vitro, in vivo and clinical studies. The search identified sutezolid, tedizolid, delpazolid, eperezolid, radezolid, contezolid, posizolid and TBI-223, in addition to linezolid. An additional search resulted in 32 preclinical and 21 clinical studies. All novel oxazolidinones except posizolid and eperezolid resulted in positive preclinical outcomes. Sutezolid and delpazolid completed early phase 2 clinical studies with better safety and equal or superior efficacy. Linezolid is expected to continue as the mainstay therapy, with renewed interest in drug monitoring. Sutezolid, tedizolid, delpazolid and TBI-223 displayed promising preliminary results. Further clinical studies would be required to assess the safety profiles and optimize the dosing regimens.
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These authors contributed equally to this work.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics16060818