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

Deepak Almeida, Si Yang Li, Jin Lee, Barry Hafkin, Khisimuzi Mdluli, Nader Fotouhi, Eric L. Nuermberger

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalAntimicrobial agents and chemotherapy
Volume67
Issue number12
DOIs
StatePublished - Dec 2023

Keywords

  • Mycobacterium tuberculosis
  • contezolid
  • oxazolidinones

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases
  • Pharmacology

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