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. 2023 Dec 14;67(12):e0078923.
doi: 10.1128/aac.00789-23. Epub 2023 Nov 15.

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

Deepak Almeida  1 , Si-Yang Li  1 , Jin Lee  1 , Barry Hafkin  2 , Khisimuzi Mdluli  3 , Nader Fotouhi  3 , Eric L Nuermberger  1
Affiliations

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

Deepak Almeida et al. Antimicrob Agents Chemother. .

Abstract

Contezolid is a new oxazolidinone with in vitro and in vivo activity against Mycobacterium tuberculosis 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 in vitro had 32- to 64-fold increases in contezolid MIC and harbored mutations in the mce3R 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.

Keywords: Mycobacterium tuberculosis; contezolid; oxazolidinones.

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Conflict of interest statement

Barry Hafkin is an employee of MicuRx Pharmaceuticals, Khisimuzi Mdluli is an employee of the Bill & Melinda Gates Medical Research Institute, and Nader Fotouhi is an employee of the Global Alliance for Tuberculosis Drug Development.

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