Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections
Dereje A. Negatu, Wassihun Wedajo Aragaw, Julianna Cangialosi, Véronique Dartois, Thomas Dick
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.
Topics & Concepts
LinezolidTuberculosisMycobacterium tuberculosisNontuberculous mycobacteriaMedicineMycobacteriumAntibioticsMicrobiologyBiologyStaphylococcus aureusBacteriaPathologyVancomycinGeneticsMycobacterium research and diagnosisTuberculosis Research and EpidemiologyInfectious Diseases and Tuberculosis