2. Academic Validation
  3. Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections

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

  • Antimicrob Agents Chemother. 2023 Mar 15;e0165522. doi: 10.1128/aac.01655-22.
Dereje A Negatu 1 2,  Wassihun Wedajo Aragaw 1,  Julianna Cangialosi 1,  Véronique Dartois 1 3,  Thomas Dick 1 3 4
Affiliations

Affiliations

  • 1 Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
  • 2 Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia.
  • 3 Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
  • 4 Department of Microbiology and Immunology, Georgetown University, Washington, DC, USA.
PMID: 36920191 DOI: 10.1128/aac.01655-22
Abstract

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.

Keywords

mitochondrial toxicity; nontuberculous mycobacteria; oxazolidinone; tuberculosis.

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