National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Department of Respiratory Medicine, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou Province, China.
Antimicrob Agents Chemother. 2018 Jul 27;62(8). doi: 10.1128/AAC.00165-18. Print 2018 Aug.
Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant In this study, we compared the activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, , and genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC values for isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates ( > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group ( = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within that endowed with linezolid, but not delpazolid, resistance was identified.
唑烷酮类药物在治疗分枝杆菌感染方面非常有效，包括由耐药引起的结核病（TB）。在这项研究中，我们比较了新型唑烷酮类药物 delpazolid 与利奈唑胺对中国耐多药结核病（MDR-TB）和广泛耐药结核病（XDR-TB）的活性和 MIC 分布。此外，还分析了 23S rRNA、和 基因中的基因突变，以揭示观察到的唑烷酮类药物耐药的潜在机制。本研究共纳入 240 株分离株，包括 120 株 MDR-TB 分离株和 120 株 XDR-TB 分离株。总体而言，分离株的利奈唑胺和 delpazolid MIC 值分别为 0.25 mg/L 和 0.5 mg/L。基于目视检查，我们暂定将 MIC 测定的流行病学截断值（ECOFF）值设定为利奈唑胺和 delpazolid 分别为 1.0 mg/L 和 2.0 mg/L。尽管在 XDR-TB 分离株中，利奈唑胺和 delpazolid 的耐药率没有显著差异（>0.05），但统计分析显示，在 MDR-TB 组中，利奈唑胺耐药分离株的比例明显高于 delpazolid 耐药分离株（=0.036）。在 13 株利奈唑胺耐药分离株中，有 7 株（53.85%）发现三个靶基因内存在突变。此外，1 株分离株在编码蛋白的 内表现出氨基酸取代（Arg126His），导致对利奈唑胺（MIC>16 mg/L）表现出高水平耐药，而对 delpazolid 的 MIC 为 0.25。总之，药敏试验显示 delpazolid 的抗菌活性与利奈唑胺相当。鉴定出一种新型突变赋予 对利奈唑胺的耐药性，但对 delpazolid 耐药性。
