Department of Medicine, Johns Hopkins University Center for Tuberculosis Research, Baltimore, Maryland, USA.
MicuRx Pharmaceuticals, Foster City, California, USA.
Antimicrob Agents Chemother. 2023 Dec 14;67(12):e0078923. doi: 10.1128/aac.00789-23. Epub 2023 Nov 15.
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.
康替唑胺是一种新型噁唑烷酮类药物，对 和 具有与利奈唑胺相当的 活性。临床前和临床安全性研究表明，它的毒性可能低于利奈唑胺，使康替唑胺成为治疗耐药性结核病替代利奈唑胺的潜在候选药物。我们评估了康替唑胺单药和与贝达喹啉和普托马尼联合用药的剂量范围活性，并与类似剂量的利奈唑胺进行了比较，在已建立的 BALB/c 小鼠结核病模型中进行了比较。康替唑胺的 MIC 为 1 µg/mL，与利奈唑胺相似，在小鼠中也表现出相似的杀菌活性。康替唑胺耐药突变体的 MIC 增加了 32 至 64 倍，并且携带 基因中的突变。这些突变体对利奈唑胺没有交叉耐药性。我们的研究结果表明，康替唑胺有可能替代包含贝达喹啉和普托马尼的方案以及可能的其他方案中的利奈唑胺。
