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突变与乙硫异烟胺敏感性的相关性:来自国家结核病参考中心的经验

Correlation of mutations and ethionamide susceptibility: Experience from national reference center for tuberculosis.

作者信息

Sarin Rohit, Bhalla Manpreet, Kumar Gavish, Singh Anjali, Myneedu Vithal Prasad, Singhal Ritu

机构信息

Department of Tuberculosis and Chest, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India.

Department of Microbiology, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India.

出版信息

Lung India. 2021 Nov-Dec;38(6):520-523. doi: 10.4103/lungindia.lungindia_120_21.

DOI:10.4103/lungindia.lungindia_120_21
PMID:34747732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8614619/
Abstract

BACKGROUND

Detection of ethionamide (ETH) resistance is crucial as it is part of antitubercular regime. It is crucial to examine the role of inhA gene mutations as a surrogate marker for the detection of ETH resistance, in the Indian context. The present retrospective study was designed with this objective.

SUBJECTS AND METHODS

The study was conducted in National Reference Laboratory within the tertiary care institute from January 1, 2018, to June 30, 2019, over 18 months duration. A total of 6612 sputum samples from presumptive multidrug-resistant tuberculosis (TB) patients were received from four districts of Delhi, outdoor and inpatients. Line probe assay (LPA) was performed for smear-positive or culture-positive samples for Mycobacterium tuberculosis. All isolates found to be INH resistant by LPA were cultured and phenotypic susceptibility to ETH was conducted for selected isolates as per the guidelines.

RESULTS

A total of 246 isolates were analyzed, for which phenotypic susceptibility to ETH and mutations in inhA were available. ETH resistance was detected among 87/108 (80.5%) isolates with inhA mutation. Sensitivity and specificity of inhA mutation for detection of ETH resistance were 80.5% and 83.8%, respectively. No inhA mutation was detected in 29/116 (25%) ETH-resistant isolates in our study, whereas ETH was found to be phenotypically susceptible in spite of the presence of inhA mutation among 21/130 (16.1%) isolates.

CONCLUSIONS

Mutations in inhA gene in LPA predict ETH resistance with fairly good sensitivity and specificity. However, it is imperative to perform phenotypic detection of ETH resistance at proper concentration, in addition to detecting inhA mutation.

摘要

背景

乙硫异烟胺(ETH)耐药性检测至关重要,因为它是抗结核治疗方案的一部分。在印度的背景下,研究inhA基因突变作为ETH耐药性检测替代标志物的作用至关重要。本回顾性研究就是以此为目的设计的。

受试者与方法

该研究于2018年1月1日至2019年6月30日在三级医疗机构的国家参考实验室进行,为期18个月。从德里四个区的门诊和住院疑似耐多药结核病(TB)患者中总共接收了6612份痰标本。对涂片阳性或培养阳性的结核分枝杆菌样本进行线性探针分析(LPA)。所有通过LPA检测发现对异烟肼(INH)耐药的分离株均进行培养,并根据指南对选定的分离株进行ETH的表型药敏试验。

结果

总共分析了246株分离株,这些分离株有ETH的表型药敏试验结果和inhA基因突变情况。在108株有inhA基因突变的分离株中,检测到87株(80.5%)对ETH耐药。inhA基因突变检测ETH耐药性的敏感性和特异性分别为80.5%和83.8%。在本研究中,116株ETH耐药分离株中有29株(25%)未检测到inhA基因突变,而在130株分离株中有21株(16.1%)尽管存在inhA基因突变,但ETH表型药敏试验结果显示敏感。

结论

LPA中inhA基因的突变对ETH耐药性具有较好的预测敏感性和特异性。然而,除了检测inhA基因突变外,还必须在适当浓度下进行ETH耐药性的表型检测。

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Int J Tuberc Lung Dis. 2016 Aug;20(8):1099-104. doi: 10.5588/ijtld.15.0864.
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Revisiting the susceptibility testing of Mycobacterium tuberculosis to ethionamide in solid culture medium.重新审视结核分枝杆菌在固体培养基中对乙硫异烟胺的药敏试验。
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Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates.结核分枝杆菌临床分离株中与对异烟肼和乙硫异烟胺的独立耐药性及交叉耐药性相关基因的基因型分析
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