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

Antimicrobial agents and chemotherapy, Volume: 67, Issue: 4
April 18, 2023
Dereje A Negatu DA, Wassihun Wedajo Aragaw WW, Julianna Cangialosi J, VĂ©ronique Dartois V, Thomas Dick T

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.

Courtesy of the U.S. National Library of Medicine