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美国结核分枝杆菌复合群乙胺丁醇耐药性的分子与基于生长的药敏试验

Molecular and Growth-Based Drug Susceptibility Testing of Mycobacterium tuberculosis Complex for Ethambutol Resistance in the United States.

作者信息

Yakrus Mitchell A, Driscoll Jeffrey, McAlister Allison, Sikes David, Hartline Denise, Metchock Beverly, Starks Angela M

机构信息

Centers for Disease Control and Prevention, Atlanta, GA 30329-4027, USA.

出版信息

Tuberc Res Treat. 2016;2016:3404860. doi: 10.1155/2016/3404860. Epub 2016 Jun 8.

DOI:10.1155/2016/3404860
PMID:27375902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4916310/
Abstract

Ethambutol (EMB) is used as a part of drug regimens for treatment of tuberculosis (TB). Susceptibility of Mycobacterium tuberculosis complex (MTBC) isolates to EMB can be discerned by DNA sequencing to detect mutations in the embB gene associated with resistance. US Public Health Laboratories (PHL) primarily use growth-based drug susceptibility test (DST) methods to determine EMB resistance. The Centers for Disease Control and Prevention (CDC) provides a service for molecular detection of drug resistance (MDDR) by DNA sequencing and concurrent growth-based DST using agar proportion. PHL and CDC test results were compared for 211 MTBC samples submitted to CDC from September 2009 through February 2011. Concordance between growth-based DST results from PHL and CDC was 88.2%. A growth-based comparison of 39 samples, where an embB mutation associated with EMB resistance was detected, revealed a higher percentage of EMB resistance by CDC (84.6%) than by PHL (59.0%) which was significant (P value = 0.002). Discordance between all growth-based test results from PHL and CDC was also significant (P value = 0.003). Most discordance was linked to false susceptibility using the BACTEC™ MGIT™ 960 (MGIT) growth-based system. Our analysis supports coalescing growth-based and molecular results for an informed interpretation of potential EMB resistance.

摘要

乙胺丁醇(EMB)被用作治疗结核病(TB)药物方案的一部分。结核分枝杆菌复合群(MTBC)分离株对EMB的敏感性可通过DNA测序来检测与耐药相关的embB基因突变来辨别。美国公共卫生实验室(PHL)主要使用基于生长的药敏试验(DST)方法来确定EMB耐药性。疾病控制与预防中心(CDC)提供一项通过DNA测序和使用琼脂比例法的同步基于生长的DST进行耐药性分子检测(MDDR)的服务。对2009年9月至2011年2月提交给CDC的211份MTBC样本的PHL和CDC检测结果进行了比较。PHL和CDC基于生长的DST结果之间的一致性为88.2%。对39份检测到与EMB耐药相关的embB突变的样本进行基于生长的比较,结果显示CDC检测到的EMB耐药百分比(84.6%)高于PHL(59.0%),差异具有统计学意义(P值 = 0.002)。PHL和CDC所有基于生长的检测结果之间的不一致性也具有统计学意义(P值 = 0.003)。大多数不一致性与使用BACTEC™ MGIT™ 960(MGIT)基于生长的系统出现的假敏感性有关。我们的分析支持将基于生长的结果和分子结果结合起来,以便对潜在的EMB耐药性进行明智的解读。

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Molecular Analysis of the embCAB Locus and embR Gene Involved in Ethambutol Resistance in Clinical Isolates of Mycobacterium tuberculosis in France.法国结核分枝杆菌临床分离株中与乙胺丁醇耐药性相关的embCAB基因座和embR基因的分子分析
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Ethambutol resistance as determined by broth dilution method correlates better than sequencing results with embB mutations in multidrug-resistant Mycobacterium tuberculosis isolates.肉汤稀释法测定的乙胺丁醇耐药性与耐多药结核分枝杆菌分离株中 embB 突变的测序结果相关性更好。
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Discordance across several methods for drug susceptibility testing of drug-resistant Mycobacterium tuberculosis isolates in a single laboratory.单实验室中几种耐药结核分枝杆菌分离株药物敏感性检测方法的不一致性。
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