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

Almeida, D. V.; Li, S.-Y.; Lee, J.; Hafkin, B.; Mdluli, K.; Fotouhi, N.; Nuermberger, E.

doi:10.1101/2023.06.18.545492

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bioRxiv · 10.1101/2023.06.18.545492

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

Almeida, D. V.·Li, S.-Y.·Lee, J.·Hafkin, B.·Mdluli, K.·Fotouhi, N.·Nuermberger, E.

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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 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 {micro}g/ml, similar to linezolid, and exhibited similar bactericidal activity in mice. Contezolid-resistant mutants selected in vitro had 10-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 potential to replace linezolid in regimens containing bedaquiline and pretomanid and likely other regimens.

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Almeida, D. V., Li, S.-Y., Lee, J., Hafkin, B., Mdluli, K., Fotouhi, N., Nuermberger, E.. 2023-06-19. Contezolid can replace linezolid in a novel combination with bedaquiline and pretomanid in a murine model of tuberculosis. https://doi.org/10.1101/2023.06.18.545492

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