Non-actionable Results, Accuracy, and Effect of First- and Second-line Line Probe Assays for Diagnosing Drug-Resistant Tuberculosis, Including on Smear-Negative Specimens, in a High-Volume Laboratory.
Non-actionable Results, Accuracy, and Effect of First- and Second-line Line Probe Assays for Diagnosing Drug-Resistant Tuberculosis, Including on Smear-Negative Specimens, in a High-Volume Laboratory.
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DOI：
10.1093/cid/ciac556
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发表时间：
2023-02-08
期刊：
影响因子：
--
通讯作者：
Theron G
中科院分区：
文献类型：
--
作者：
Pillay S;de Vos M;Derendinger B;Streicher EM;Dolby T;Scott LA;Steinhobel AD;Warren RM;Theron G
快速药敏试验(DST)对于确认新的结核病(TB)方案是否合格至关重要。基因MTBDRsl是世界卫生组织(WHO)认可的一种广泛部署的检测方法，但程序性的性能数据，包括涂片阴性痰的不可操作结果，却很少。在常规实验室用MTBDRplus和MTBDRsl(均为v2)对951例对MTB/RIF-利福平耐药个体的Sputa进行了检测。表型DST为二线药物参考标准。不一致的结果进行了Sanger测序。89%(849/951)为培养阳性[56%(476/849)为涂片阴性]。在19%(92/476)的涂片阴性病例中，MTBDRplus至少有一个不可操作的结果(对照和/或结核检测条带缺失或无效，排除了耐药性报告)，而对于MTBDRs1，40%(171/427)是不可操作的[28%(120/427)假阴性结核，17%(51/427)不确定]。在涂片阴性中，MTBDRs1对氟喹诺酮类药物的敏感度为84%(95%CI 67-93)，对二线注射剂的敏感度为81%(54-95)，对两者的敏感度均为57%(28-82)。特异性分别为93%(89-98)、88%(81-93)和97%(91-99)。23%(172/746)的Xpert利福平耐药标本对MTBDR+异烟肼敏感。随着MTBDRs1方案的出现，天数到二线敏感性报告有所改善[6(5-7)对37(35-46)；p<；0.001]。MTBDRsl在几乎一半的涂片阴性患者中没有产生结果(4/10失败)，导致大量错过耐药。然而，如果MTBDRsl产生一个可操作的结果，则该结果在统治二线阻力方面是准确的。异烟肼药敏试验仍然至关重要。这项研究在世卫组织指南的背景下，提供了关于非可操作结果(如果无法解释，将导致对检测效用的高估)、准确性和护理级联影响的真实世界直接二线药敏检测性能数据。
Rapid drug susceptibility testing (DST) is crucial to confirm eligibility for new tuberculosis (TB) regimens. Genotype MTBDRsl is a widely-deployed World Health Organization (WHO)-endorsed assay yet programmatic performance data, including non-actionable results from smear-negative sputum, are scarce. Sputa from Xpert MTB/RIF-rifampicin resistant individuals (n=951) were tested by Genotype MTBDRplus and MTBDRsl (both v2) in a routine laboratory. Phenotypic DST was the second-line drug reference standard. Discrepant results underwent Sanger sequencing. 89% (849/951) individuals were culture-positive [56% (476/849) smear-negative]. MTBDRplus had at least one non-actionable result (control and/or TB-detection bands absent or invalid, precluding resistance reporting) in 19% (92/476) of smear-negatives and, for MTBDRsl, 40% (171/427) were non-actionable [28% (120/427) false-negative TB, 17% (51/427) indeterminate]. In smear-negatives, MTBDRsl sensitivity for fluoroquinolones was 84% (95% CI 67-93), 81% (54-95) for second-line injectables, and 57% (28-82) for both. Specificities were 93% (89-98), 88% (81-93), and 97% (91-99), respectively. 23% (172/746) of Xpert rifampicin-resistant specimens were MTBDRplus isoniazid-susceptible. Days-to-second-line-susceptibility reporting with the programmatic advent of MTBDRsl improved [6 (5-7) vs. 37 (35-46); p<0.001]. MTBDRsl did not generate a result in almost half of smear-negative individuals (4/10 failed), resulting in substantial missed resistance. However, if MTBDRsl generates an actionable result, that result is accurate in ruling-in second-line resistance. Isoniazid susceptibility testing remains crucial. This study provides, in the context of WHO guidance, real-world direct second-line susceptibility testing performance data on non-actionable results (which, if unaccounted for, result in an overestimation of test utility), accuracy, and care cascade impact.
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影响因子：
5.2
作者：
Van Rie, Annelies;Whitfield, Michael G.;Warren, Robin M.
通讯作者：
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影响因子：
6.4
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影响因子：
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作者：
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通讯作者：
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