Contezolid can replace linezolid in a novel combination with bedaquiline and pretomanid in a murine model of tuberculosis.
Deepak AlmeidaSi-Yang LiJin LeeBarry HafkinKhisimuzi MdluliNader FotouhiEric L NuermbergerPublished in: Antimicrobial agents and chemotherapy (2023)
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.
Keyphrases
- drug resistant
- mycobacterium tuberculosis
- methicillin resistant staphylococcus aureus
- multidrug resistant
- acinetobacter baumannii
- pulmonary tuberculosis
- staphylococcus aureus
- risk assessment
- cystic fibrosis
- insulin resistance
- human health
- pseudomonas aeruginosa
- dna methylation
- transcription factor
- adverse drug
- high fat diet induced
- drug induced