GenoType MTBDRplus Assay for Rapid Detection of Multidrug Resistance in Mycobacterium tuberculosis: A Meta-Analysis

BackgroundThere is an urgent demand for rapid and accurate drug-susceptibility testing for the detection of multidrug-resistant tuberculosis. The GenoType MTBDRplus assay is a promising molecular kit designed for rapid identification of resistance to first-line anti-tuberculosis drugs, isoniazid and rifampicin. The aim of this meta-analysis was to evaluate the diagnostic accuracy of GenoType MTBDRplus in detecting drug resistance to isoniazid and rifampicin in comparison with the conventional drug susceptibility tests.MethodsWe searched PubMed, EMBASE, and Cochrane Library databases to identify studies according to predetermined criteria. A total of 40 studies were included in the meta-analysis. QUADAS-2 was used to assess the quality of included studies with RevMan 5.2. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curves. Heterogeneity in accuracy measures was tested with Spearman correlation coefficient and Chi-square.ResultsPatient selection bias was observed in most studies. The pooled sensitivity (95% confidence intervals were 0.91 (0.88–0.94) for isoniazid, 0.96 (0.95–0.97) for rifampicin, and 0.91(0.86–0.94) for multidrug-resistance. The pooled specificity (95% CI) was 0.99 (0.98–0.99) for isoniazid, 0.98 (0.97–0.99) for rifampicin and 0.99 (0.99–1.00) for multidrug-resistance, respectively. The area under the summary receiver operating characteristic curves ranged from 0.99 to 1.00.ConclusionThis meta-analysis determined that GenoType MTBDRplus had good accuracy for rapid detection of drug resistance to isoniazid and/or rifampicin of M. tuberculosis. MTBDRplus method might be a good alternative to conventional drug susceptibility tests in clinical practice.

研究背景：当前亟需快速且精准的药物敏感性试验（drug-susceptibility testing）以检出耐多药结核病（multidrug-resistant tuberculosis）。GenoType MTBDRplus检测试剂盒（GenoType MTBDRplus assay）是一款极具应用前景的分子检测工具，旨在快速鉴定结核分枝杆菌对一线抗结核药物异烟肼（isoniazid）与利福平（rifampicin）的耐药性。本项荟萃分析旨在评估GenoType MTBDRplus检测试剂盒相较于传统药物敏感性试验，在检出异烟肼与利福平耐药性方面的诊断准确性。
研究方法：我们通过检索PubMed、EMBASE及Cochrane Library数据库，依据预先设定的纳入标准筛选相关研究。最终共有40项研究纳入本次荟萃分析。采用RevMan 5.2软件，通过QUADAS-2工具对纳入研究的质量进行评价。采用STATA 13.0软件分析各项研究的灵敏度（sensitivity）、特异度（specificity）、阳性似然比（positive likelihood ratio）、阴性似然比（negative likelihood ratio）、诊断比值比（diagnostic odds ratio）以及汇总受试者工作特征曲线下面积（area under the summary receiver operating characteristic curves）。采用Spearman相关系数及卡方检验对诊断准确性指标的异质性进行分析。
研究结果：多数研究存在患者选择偏倚。异烟肼的合并灵敏度为0.91（95%置信区间：0.88~0.94），利福平的合并灵敏度为0.96（95%置信区间：0.95~0.97），耐多药状态的合并灵敏度为0.91（95%置信区间：0.86~0.94）。异烟肼的合并特异度为0.99（95%置信区间：0.98~0.99），利福平的合并特异度为0.98（95%置信区间：0.97~0.99），耐多药状态的合并特异度为0.99（95%置信区间：0.99~1.00）。汇总受试者工作特征曲线下面积介于0.99至1.00之间。
研究结论：本次荟萃分析结果显示，GenoType MTBDRplus检测试剂盒在快速检出结核分枝杆菌（Mycobacterium tuberculosis）对异烟肼和/或利福平的耐药性方面具有良好的诊断准确性。在临床实践中，GenoType MTBDRplus检测方法可作为传统药物敏感性试验的理想替代方案。