Huang Wei-Lun, Chen Huang-Yau, Kuo Yuh-Min, Jou Ruwen
Research and Diagnostic Center, Centers for Disease Control, Taipei, Taiwan, Republic of China.
J Clin Microbiol. 2009 Aug;47(8):2520-4. doi: 10.1128/JCM.02499-08. Epub 2009 Jun 3.
To facilitate the management of multidrug-resistant (MDR) tuberculosis, two nucleic acid sequence-based methods, the GenoType MTBDRplus test and DNA sequencing, were assessed for the rapid detection of drug-resistant Mycobacterium tuberculosis for the first time in the Asia-Pacific region. The performances of these two assays in detecting the presence of rifampin (rifampicin) (RIF) and isoniazid (INH) resistance-associated mutations in the rpoB, katG, inhA regulatory region, inhA, and oxyR-ahpC genes were compared to that of a conventional agar proportion drug susceptibility test. A total of 242 MDR and 30 pansusceptible M. tuberculosis isolates were evaluated in this study. The sensitivities obtained for RIF-resistant detection by the GenoType MTBDRplus test and by resistance gene sequencing were 95.5% and 97.9%, respectively. The sensitivities for INH resistance detection by the GenoType MTBDRplus test and by resistance gene sequencing were 81.8% and 93.4%, respectively. Together, the sensitivity for MDR tuberculosis detection was 78.5% with the GenoType MTBDRplus test and 91.3% by resistance gene sequencing. The specificity for RIF resistance, INH resistance, and MDR detection was 100% by both methods. The GenoType MTBDRplus test has the advantage of a short turnaround time for drug-resistant M. tuberculosis detection. Overall, the two assays performed equally well in detecting RIF resistance (P = 0.13). However, DNA sequencing demonstrated superior performance in detecting INH resistance (P < 0.001) and MDR tuberculosis (P < 0.001). We suggest that new alleles of INH resistance genes should be evaluated to improve the sensitivity of the GenoType MTBDRplus test, especially for different geographic areas with genetically diverse M. tuberculosis strains.
为促进耐多药结核病的管理，在亚太地区首次对两种基于核酸序列的方法——GenoType MTBDRplus检测法和DNA测序法——用于快速检测耐药结核分枝杆菌进行了评估。将这两种检测方法在检测rpoB、katG、inhA调控区、inhA以及oxyR-ahpC基因中利福平（rifampicin，RIF）和异烟肼（INH）耐药相关突变方面的性能，与传统的琼脂比例法药物敏感性试验进行了比较。本研究共评估了242株耐多药结核分枝杆菌和30株全敏感结核分枝杆菌分离株。GenoType MTBDRplus检测法和耐药基因测序法检测RIF耐药的敏感性分别为95.5%和97.9%。GenoType MTBDRplus检测法和耐药基因测序法检测INH耐药的敏感性分别为81.8%和93.4%。总体而言，GenoType MTBDRplus检测法检测耐多药结核病的敏感性为78.5%，耐药基因测序法为91.3%。两种方法检测RIF耐药、INH耐药和耐多药的特异性均为100%。GenoType MTBDRplus检测法在检测耐药结核分枝杆菌方面具有周转时间短的优势。总体而言，两种检测方法在检测RIF耐药方面表现相当（P = 0.13）。然而，DNA测序在检测INH耐药（P < 0.001）和耐多药结核病（P < 0.001）方面表现更优。我们建议应评估INH耐药基因的新等位基因，以提高GenoType MTBDRplus检测法的敏感性，特别是对于结核分枝杆菌菌株基因多样的不同地理区域。
