Rapid molecular detection of tuberculosis and rifampin resistance.
Rapid molecular detection of tuberculosis and rifampin resistance.
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DOI：
10.1056/nejmoa0907847
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发表时间：
2010-09-09
期刊：
影响因子：
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通讯作者：
Perkins MD
中科院分区：
文献类型：
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作者：
Boehme CC;Nabeta P;Hillemann D;Nicol MP;Shenai S;Krapp F;Allen J;Tahirli R;Blakemore R;Rustomjee R;Milovic A;Jones M;O'Brien SM;Persing DH;Ruesch-Gerdes S;Gotuzzo E;Rodrigues C;Alland D;Perkins MD
结核病的全球控制受到诊断方法缓慢、不敏感的阻碍，特别是在检测耐药形式和人类免疫缺陷病毒感染患者方面。早期检测对于降低死亡率和阻断传播至关重要，但敏感方法的复杂性和基础设施需求限制了其可获得性和效果。我们在1730例疑似药物敏感或耐多药肺结核患者中评估了Xpert MTB/RIF（结核分枝杆菌（MTB）和利福平耐药性（RIF）的自动化分子检测试剂盒）的性能，该试剂盒具有完全集成的样本处理功能。秘鲁、阿塞拜疆、南非和印度的合格患者各提供3份痰液标本。在显微镜检查、固体和液体培养以及MTB/RIF试验之前，用N-乙酰基-L-半胱氨酸和氢氧化钠处理两个标本，一个标本用于直接用显微镜检查和MTB/RIF试验进行检测。在培养阳性患者中，单次直接MTB/RIF检测确定了561例涂片阳性结核病患者中的551例（98.2%）和171例涂片阴性结核病患者中的124例（72.5%）。在609例非结核病患者中，604例（99.2%）的试验具有特异性。在涂片阴性、培养阳性的结核病患者中，增加第二次MTB/RIF检测使敏感性提高了12.6个百分点，第三次提高了5.1个百分点，总敏感性达到90.2%。与表型药敏试验相比，MTB/RIF试验正确识别了205例患者中的200例（97.6%）利福平耐药菌和514例患者中的504例（98.1%）利福平敏感菌。测序解决了除两例以外的所有病例，有利于MTB/RIF测定。MTB/RIF检测可在不到2小时的时间内直接从未经治疗的痰液中敏感地检测出结核病和利福平耐药性，且操作时间最短。（由创新新诊断基金会资助。
Global control of tuberculosis is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms and in patients with human immunodeficiency virus infection. Early detection is essential to reduce the death rate and interrupt transmission, but the complexity and infrastructure needs of sensitive methods limit their accessibility and effect. We assessed the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), with fully integrated sample processing in 1730 patients with suspected drug-sensitive or multidrug-resistant pulmonary tuberculosis. Eligible patients in Peru, Azerbaijan, South Africa, and India provided three sputum specimens each. Two specimens were processed with N-acetyl-l-cysteine and sodium hydroxide before microscopy, solid and liquid culture, and the MTB/RIF test, and one specimen was used for direct testing with microscopy and the MTB/RIF test. Among culture-positive patients, a single, direct MTB/RIF test identified 551 of 561 patients with smear-positive tuberculosis (98.2%) and 124 of 171 with smear-negative tuberculosis (72.5%). The test was specific in 604 of 609 patients without tuberculosis (99.2%). Among patients with smear-negative, culture-positive tuberculosis, the addition of a second MTB/RIF test increased sensitivity by 12.6 percentage points and a third by 5.1 percentage points, to a total of 90.2%. As compared with phenotypic drug-susceptibility testing, MTB/RIF testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant bacteria and 504 of 514 (98.1%) with rifampin-sensitive bacteria. Sequencing resolved all but two cases in favor of the MTB/RIF assay. The MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2 hours with minimal hands-on time. (Funded by the Foundation for Innovative New Diagnostics.)