A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical <i>Mycobacterium tuberculosis</i> Isolates in Moscow, Russia

Background The goal of this study was to compare the consistency of three assays for the determination of the drug resistance of Mycobacterium tuberculosis (MTB) strains with various resistance profiles isolated from the Moscow region. Methods A total of 144 MTB clinical isolates with a strong bias toward drug resistance were examined using Bactec MGIT 960, Sensititre MycoTB, and a microarray-based molecular assay TB-TEST to detect substitutions in the rpoB, katG, inhA, ahpC, gyrA, gyrB, rrs, eis, and embB genes that are associated with resistance to rifampin, isoniazid, fluoroquinolones, second-line injectable drugs and ethambutol. Results The average correlation for the identification of resistant and susceptible isolates using the three methods was approximately 94%. An association of mutations detected with variable resistance levels was shown. We propose a change in the breakpoint minimal inhibitory concentration for kanamycin to less than 5 μg/ml in the Sensititre MycoTB system. A pairwise comparison of the minimal inhibitory concentrations (MICs) of two different drugs revealed an increased correlation in the first-line drug group and a partial correlation in the second-line drug group, reflecting the history of the preferential simultaneous use of drugs from these groups. An increased correlation with the MICs was also observed for drugs sharing common resistance mechanisms. Conclusions The quantitative measures of phenotypic drug resistance produced by the Sensititre MycoTB and the timely detection of mutations using the TB-TEST assay provide guidance for clinicians for the choice of the appropriate drug regimen.背景 本研究旨在比对三种检测方法的一致性，以鉴定从莫斯科地区分离的、携带不同耐药谱的结核分枝杆菌（Mycobacterium tuberculosis, MTB）菌株的耐药性。 方法 本研究共纳入144株临床分离的结核分枝杆菌菌株，此类菌株显著偏向耐药表型；采用Bactec MGIT 960、Sensititre MycoTB及基于微阵列的分子检测方法TB-TEST进行检测，以定位与利福平、异烟肼、氟喹诺酮类、二线注射类药物及乙胺丁醇耐药相关的rpoB、katG、inhA、ahpC、gyrA、gyrB、rrs、eis及embB基因的碱基替换突变。 结果 三种方法对耐药菌株与敏感菌株的鉴定平均一致性约为94%。本研究证实了所检测到的突变与不同耐药水平之间存在关联。我们建议调整Sensititre MycoTB系统中卡那霉素的最低抑菌浓度（minimal inhibitory concentration, MIC）折点，将其设定为小于5 μg/ml。对两种不同药物的最低抑菌浓度（MIC）进行两两比较后发现，一线药物组的相关性有所提升，二线药物组则呈现部分相关性，这反映了临床中优先联合使用这两类药物的既往用药史。此外，具有共同耐药机制的药物，其MIC值之间的相关性也有所升高。 结论 Sensititre MycoTB系统所得到的表型耐药定量检测结果，以及TB-TEST检测方法对突变的及时检出，可为临床医师选择合适的用药方案提供指导。