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
  • 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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