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

Tuberculosis Research and Treatment Pub Date : 2016-01-01 Epub Date: 2016-06-08 DOI:10.1155/2016/3404860
Mitchell A Yakrus, Jeffrey Driscoll, Allison McAlister, David Sikes, Denise Hartline, Beverly Metchock, Angela M Starks
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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.

美国结核分枝杆菌对乙胺丁醇耐药性的分子和基于生长的药物敏感性测试。
乙胺丁醇(EMB)是治疗结核病(TB)的药物方案之一。结核分枝杆菌(MTBC)分离株对 EMB 的敏感性可通过 DNA 测序来鉴别,以检测与耐药性相关的 embB 基因突变。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。美国疾病控制与预防中心(CDC)提供的耐药性分子检测(MDDR)服务是通过DNA测序和同时使用琼脂比例的生长型药敏试验(DST)进行的。我们比较了 PHL 和 CDC 对 2009 年 9 月至 2011 年 2 月期间提交给 CDC 的 211 份 MTBC 样品的检测结果。PHL 和 CDC 基于生长的 DST 检测结果的一致性为 88.2%。对检测到与 EMB 耐药性相关的 embB 突变的 39 份样本进行了基于生长的比较,结果显示 CDC 的 EMB 耐药性比例(84.6%)高于 PHL(59.0%),差异显著(P 值 = 0.002)。PHL 和 CDC 基于生长的所有检测结果之间的不一致性也很显著(P 值 = 0.003)。大多数不一致与使用 BACTEC™ MGIT™ 960 (MGIT) 生长检测系统的错误易感性有关。我们的分析支持将基于生长的结果与分子结果结合起来,以便对潜在的 EMB 耐药性做出明智的解释。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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审稿时长
17 weeks
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