Gardee Y, Dreyer A W, Koornhof H J, Omar S V, da Silva P, Bhyat Z, Ismail N A
Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa
Department of Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
J Clin Microbiol. 2017 Mar;55(3):791-800. doi: 10.1128/JCM.01865-16. Epub 2016 Dec 14.
Early detection of resistance to second-line antituberculosis drugs is important for the management of multidrug-resistant tuberculosis (MDR-TB). The GenoType MTBDR version 2.0 (VER 2.0) line probe assay has been redesigned for molecular detection of resistance-conferring mutations of fluoroquinolones (FLQ) ( and genes) and second-line injectable drugs (SLID) ( and genes). The study evaluated the diagnostic performance of the GenoType MTBDR VER 2.0 assay for the detection of second-line drug resistance compared with phenotypic drug susceptibility testing (DST), using the Bactec MGIT 960 system on complex isolates from South Africa. A total of 268 repository isolates collected between 2012 and 2014, which were rifampin monoresistant or MDR based on DST, were selected. MTBDR VER 2.0 testing was performed on these isolates and the results analyzed. The MTBDR VER 2.0 sensitivity and specificity indices for culture isolates were the following: FLQ, 100% (95% confidence interval [CI] 95.8 to 100%) and 98.9% (95% CI, 96.1 to 99.9%); SLID, 89.2% (95% CI, 79.1 to 95.6%) and 98.5% (95% CI, 95.7 to 99.7%). The sensitivity and specificity observed for individual SLID were the following: amikacin, 93.8% (95% CI, 79.2 to 99.2%) and 98.5% (95% CI, 95.5 to 99.7%); kanamycin, 89.2% (95% CI, 79.1 to 95.6%) and 98.5% (95% CI, 95.5 to 99.7%); and capreomycin, 86.2% (95% CI, 68.3 to 96.1%) and 95.9% (95% CI, 92.2 to 98.2%). An interoperator reproducibility of 100% and an overall interlaboratory performance of 93% to 96% were found. The overall improvement in sensitivity and specificity with excellent reproducibility makes the GenoType MTBDR VER 2.0 a highly suitable tool for rapid screening of clinical isolates for second-line drug resistance for use in high-burden TB/HIV settings.
早期检测对二线抗结核药物的耐药性对于耐多药结核病（MDR-TB）的管理至关重要。GenoType MTBDR版本2.0（VER 2.0）线性探针检测法已重新设计，用于分子检测氟喹诺酮类（FLQ）（ 和 基因）及二线注射用药物（SLID）（ 和 基因）的耐药性突变。本研究使用Bactec MGIT 960系统，评估了GenoType MTBDR VER 2.0检测法与表型药物敏感性试验（DST）相比，对南非复杂分离株二线耐药性检测的诊断性能。共选择了2012年至2014年间收集的268株储存分离株，这些分离株基于DST为单耐利福平或耐多药。对这些分离株进行MTBDR VER 2.0检测并分析结果。培养分离株的MTBDR VER 2.0敏感性和特异性指标如下：FLQ，100%（95%置信区间[CI]95.8至100%）和98.9%（95%CI，96.1至99.9%）；SLID，89.2%（95%CI，79.1至95.6%）和98.5%（95%CI，95.7至99.7%）。各SLID观察到的敏感性和特异性如下：阿米卡星，93.8%（95%CI，79.2至99.2%）和98.5%（95%CI，95.5至99.7%）；卡那霉素，89.2%（95%CI，79.1至95.6%）和98.5%（95%CI，95.5至99.7%）；卷曲霉素，86.2%（95%CI，68.3至96.1%）和95.9%（95%CI，92.2至98.2%）。发现操作者间重复性为100%，实验室间总体性能为93%至96%。敏感性和特异性的总体提高以及出色的重复性使得GenoType MTBDR VER 2.0成为在高负担结核病/艾滋病环境中快速筛查临床分离株二线耐药性的高度适用工具。
