Contezolid can replace linezolid in a novel combination with bedaquiline and pretomanid in a murine model of tuberculosis.

Antimicrobial agents and chemotherapy, Volume: 67, Issue: 12
December 14, 2023
Deepak Almeida D, Si-Yang Li S-Y, Jin Lee J, Barry Hafkin B, Khisimuzi Mdluli K, Nader Fotouhi N, Eric L Nuermberger EL

Contezolid is a new oxazolidinone with and activity against comparable to that of linezolid. Pre-clinical and clinical safety studies suggest it may be less toxic than linezolid, making contezolid a potential candidate to replace linezolid in the treatment of drug-resistant tuberculosis. We evaluated the dose-ranging activity of contezolid, alone and in combination with bedaquiline and pretomanid, and compared it with linezolid at similar doses, in an established BALB/c mouse model of tuberculosis. Contezolid had an MIC of 1 µg/mL, similar to linezolid, and exhibited similar bactericidal activity in mice. Contezolid-resistant mutants selected had 32- to 64-fold increases in contezolid MIC and harbored mutations in the gene. These mutants did not display cross-resistance to linezolid. Our results indicate that contezolid has the potential to replace linezolid in regimens containing bedaquiline and pretomanid and likely other regimens.

Courtesy of the U.S. National Library of Medicine