New Delhi Tuberculosis Centre, Jawaharlal Nehru Marg, Delhi Gate, New Delhi, 110002, India.
New Delhi Tuberculosis Centre, Jawaharlal Nehru Marg, Delhi Gate, New Delhi, 110002, India.
Indian J Tuberc. 2023 Jul;70(3):361-365. doi: 10.1016/j.ijtb.2022.11.004. Epub 2022 Dec 1.
Widespread use of Fluoroquinolones (FQs) has led to the development of its resistance in clinical isolates of Mycobacterium tuberculosis. However, in Mycobacterium tuberculosis, phenotypic resistance to FQs has been shown to be heterogeneous, ranging from low-level resistance to high-level resistance. This stratification in resistance has important implications for the inclusion of moxifloxacin (Mfx) in the treatment regimen. The World Health Organization recommends the use of GenoType MTBDRsl assay as the initial test for detecting resistance conferring mutations (both high and low) to FQs in patients with confirmed MDR-RR TB. The present study was conducted to explore the relationship of MTBDRsl Version 2.0 detected mutations in gyrA gene and genotypic DST of Mfx at WHO defined Clinical Breakpoint (CB).
A total of 200 sputum samples from Confirmed MDR/RR TB patients were included in this study. All of these samples had mutations conferring resistance to FQ confirmed by GenoType MTBDRsl assay. These samples were further subjected to Phenotypic DST against moxifloxacin using the Bactec MGIT-960 system.
All of the 200 representative FQ resistant isolates had mutations in gyrA gene only with no detectable mutation in gyrB gene. 109 (54.5%) of the isolates had mutations associated with high-level increase in MIC while 91 (45.5%) isolates had mutations associated with low-level increase in MIC. Phenotypic DST of these 200 isolates against Mfx at CB (1.0μg/ml) revealed that of the 109 isolates with mutations associated with high-level increase in MIC and expected to be resistant at CB, only 34 (31.2%) were resistant and the remaining 75 (68.8%) were sensitive.
Moxifloxacin is an important drug in the regimen for treating Drug-resistant TB and the decision to exclude this drug from the regimen should not be taken merely on the basis of mutational patterns. It should rather be taken after considering the combined results of mutational analysis and phenotypic DST.
氟喹诺酮类药物（FQs）的广泛使用导致了结核分枝杆菌临床分离株的耐药性发展。然而，在结核分枝杆菌中，对 FQs 的表型耐药性表现出异质性，从低水平耐药到高水平耐药不等。这种耐药性的分层对将莫西沙星（Mfx）纳入治疗方案具有重要意义。世界卫生组织建议使用 GenoType MTBDRsl 检测法作为检测对 FQs 具有高和低耐药性的耐药相关突变（包括高和低）的初始检测方法，用于确诊的耐多药/利福平结核病（MDR-RR TB）患者。本研究旨在探索 MTBDRsl 版本 2.0 检测到的 gyrA 基因突变与 WHO 定义的临床断点（CB）下 Mfx 基因型 DST 之间的关系。
本研究共纳入 200 例确诊的耐多药/利福平结核病患者的痰样本。所有这些样本均通过 GenoType MTBDRsl 检测法证实存在对 FQ 的耐药性相关突变。这些样本进一步使用 Bactec MGIT-960 系统进行针对莫西沙星的表型 DST。
所有 200 株代表性 FQ 耐药分离株的 gyrA 基因均存在突变，而 gyrB 基因无检测到突变。109 株（54.5%）分离株的突变与 MIC 高水平升高相关，91 株（45.5%）分离株的突变与 MIC 低水平升高相关。对 200 株分离株在 CB（1.0μg/ml）下对 Mfx 的表型 DST 显示，在与 MIC 高水平升高相关且预计在 CB 下耐药的 109 株分离株中，只有 34 株（31.2%）耐药，而其余 75 株（68.8%）敏感。
莫西沙星是治疗耐药结核病方案中的重要药物，不应仅仅根据突变模式就决定将该药物从方案中排除。应在考虑突变分析和表型 DST 的综合结果后再做出决定。
