Dixit Ramakant, Mohan Emil, Gupta Ankur, Gupta Priyanka Soni, Patni Tarun, Goyal Mukesh, Meena Roshan Kumar
Department of Respiratory Medicine, J. L. N. Medical College, Ajmer, Rajasthan, India.
Department of Microbiology, J. L. N. Medical College, Ajmer, Rajasthan, India.
Int J Mycobacteriol. 2023 Jul-Sep;12(3):294-298. doi: 10.4103/ijmy.ijmy_116_23.
Fluoroquinolone (FQ) antibiotics are among the most potent second-line antitubercular drugs these days. The aim of the study was to analyze the frequency and pattern of genetic mutation in preextensive (pre-XDR) and extensively drug-resistant Mycobacterium tuberculosis using second-line line probe assay (LPA) and to compare drug-resistant mutations with different treatment outcomes.
Sputum, lymph node aspirate, and cold accesses from patients with rifampicin-resistant Tuberculosis (TB) were subjected to first-line and second-line LPA (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluoroquinolones (levofloxacin and moxifloxacin). Final treatment outcomes as per the National TB Elimination Program were assessed and compared with the mutation profile.
One hundred and fifty subjects were observed to have mutations associated with resistance to FQs and constituted the final study population. The most frequent mutation observed among GyrA drug resistance mutation was D94G (Gyr A MUT3C, 44/150, 66%) corresponding to high-level resistance to levofloxacin and moxifloxacin. The same mutation was associated with poor treatment outcome as died or treatment failure (odds ratio 2.50, relative risk 1.67, P = 0.043). The most common hetero-resistance mutation pattern observed in GyrA gene was wild type plus Asp94Gly mutation in 24.6% of isolates.
GyrA MUT3C hybridization corresponding to single-point mutation of aspartic acid to glycine at codon 94 constitutes the most common mutation in GyrA gene locus in M. tuberculosis with significant association with treatment outcome as died compared to those with treatment outcome as cured.
氟喹诺酮（FQ）类抗生素是目前最有效的二线抗结核药物之一。本研究的目的是使用二线线性探针分析（LPA）来分析广泛耐药前（pre-XDR）和广泛耐药结核分枝杆菌的基因突变频率和模式，并比较耐药突变与不同治疗结果。
对耐利福平结核病（TB）患者的痰液、淋巴结抽吸物和冷穿刺样本进行一线和二线LPA（德国海因生命科学公司的Genotype MTBDRsl），以评估对氟喹诺酮类药物（左氧氟沙星和莫西沙星）的额外耐药性。根据国家结核病消除计划评估最终治疗结果，并与突变谱进行比较。
观察到150名受试者存在与FQ耐药相关的突变，构成了最终研究人群。在GyrA耐药突变中观察到最常见的突变是D94G（Gyr A MUT3C，44/150，66%），对应于对左氧氟沙星和莫西沙星的高水平耐药。相同的突变与不良治疗结果相关，如死亡或治疗失败（比值比2.50，相对风险1.67，P = 0.043）。在GyrA基因中观察到最常见的异质耐药突变模式是野生型加Asp94Gly突变，在24.6%的分离株中出现。
GyrA MUT3C杂交对应于密码子94处天冬氨酸到甘氨酸的单点突变，是结核分枝杆菌GyrA基因位点最常见的突变，与治疗结果为死亡的患者相比，与治疗结果为治愈的患者有显著关联。
