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Diagnostic Accuracy of LiquidArray MTB-XDR VER 1.0 for the Detection of Mycobacterium tuberculosis Complex, Fluoroquinolone, Amikacin, Ethambutol, and Linezolid Susceptibility
Clinical Infectious Diseases ( IF 8.2 ) Pub Date : 2024-12-12 , DOI: 10.1093/cid/ciae614
Erick Auma 1 , Rencia Alberts 1 , Brigitta Derendinger 1 , Rouxjeane Venter 1 , Elizabeth M Streicher 1 , Samantha Pillay 1 , Yonas T Ghebrekristos 1, 2 , Moses Mburu 3 , Morten Ruhwald 3 , Robin Warren 1 , Adam Penn-Nicholson 3 , Grant Theron 1 , Margaretha de Vos 4
Affiliation  

Background Drug susceptibility testing (DST) is essential for starting people on effective tuberculosis (TB) regimens. No published data exist for the high-throughput LiquidArray MTB-XDR (LA-XDR) test, which detects Mycobacterium tuberculosis complex (MTBC) and fluoroquinolone, amikacin, ethambutol, and linezolid susceptibility (the latter 2 have no rapid DSTs available). Methods We enrolled people (N = 720) with presumptive TB who provided 2 sputum samples for an Xpert MTB/RIF Ultra assay and a culture (MTBC reference standard). Phenotypic DST and Sanger sequencing were the composite reference standards. LA-XDR on the manual FluoroLyse and automated GenoXtract fleXT (fleXT) DNA extraction methods were compared. Results For MTBC, LA-XDR had similar sensitivities (85%–87%) and specificities (99%) using each extraction method. Drug susceptibility sensitivities (95% confidence interval) varied: 94% (86%–98%) for fluoroquinolones, 64% (45%–80%) for amikacin, and 88% (79%–93%) for ethambutol (specificities of 97%–100%). Six of 7 (86%) resistant linezolid isolates were detected. LA-XDR with fleXT had indeterminate proportions of 21/251 (8%), 2/251 (1%), 63/251 (25%), and 93/251 (37%) for fluoroquinolones, ethambutol, amikacin, and linezolid, respectively (amikacin and linezolid indeterminates were higher with FluoroLyse-extracted DNA). In a hypothetical population of 100 smear-negative people with fluoroquinolone-resistant TB undergoing fleXT DNA extraction, 25 (25%) would be missed (1 extraction error, 2 invalid results, 15 MTBC-negative, 6 fluoroquinolone-indeterminate, and 1 false-susceptible). Conclusions LA-XDR met the minimum World Health Organization target product profile for a next-generation, sputum-based, moderate-complexity DST with high fluoroquinolone and ethambutol resistance sensitivity, moderate amikacin resistance sensitivity, and promise for linezolid resistance, for which more data are needed. Improved LA-XDR MTBC detection would reduce missed resistance.

中文翻译:


LiquidArray MTB-XDR VER 1.0 检测结核分枝杆菌复合物、氟喹诺酮类、阿米卡星、乙胺丁醇和利奈唑胺敏感性的诊断准确性



背景 药物敏感性测试 (DST) 对于开始接受有效的结核病 (TB) 方案至关重要。高通量 LiquidArray MTB-XDR (LA-XDR) 检测可检测结核分枝杆菌复合体 (MTBC) 和氟喹诺酮类药物、阿米卡星、乙胺丁醇和利奈唑胺敏感性(后 2 种没有可用的快速 DST),目前尚无已发表的数据。方法 我们招募了疑似结核病患者 (N = 720),他们提供 2 份痰液样本用于 Xpert MTB/RIF Ultra 检测和培养 (MTBC 参考标准)。表型 DST 和 Sanger 测序是复合参考标准。比较了手动 FluoroLyse 和自动 GenoXtract fleXT (fleXT) DNA 提取方法上的 LA-XDR。结果 对于 MTBC,使用每种提取方法的 LA-XDR 具有相似的敏感性 (85%-87%) 和特异性 (99%)。药物敏感性(95% 置信区间)各不相同:氟喹诺酮类药物为 94% (86%-98%),阿米卡星为 64% (45%-80%),乙胺丁醇为 88% (79%-93%)(特异性为 97%-100%)。检测到 7 种耐药利奈唑胺分离株中的 6 种 (86%)。氟喹诺酮类药物、乙胺丁醇、阿米卡星和利奈唑胺的不确定比例分别为 21/251 (8%) 、 2/251 (1%) 、 63/251 (25%) 和 93/251 (37%) (阿米卡星和利奈唑胺不确定物与 FluoroLyse 提取的 DNA 相比更高)。假设 100 名涂片阴性的氟喹诺酮类耐药结核病患者接受 fleXT DNA 提取,其中 25 人将被遗漏(1 名提取错误、2 名无效结果、15 名 MTBC 阴性、6 名氟喹诺酮类药物不确定和 1 名假敏感)。 结论 LA-XDR 符合世界卫生组织关于下一代、基于痰液、中等复杂性 DST 的最低目标产品概况,具有高氟喹诺酮类和乙胺丁醇耐药敏感性、中等阿米卡星耐药敏感性,并有望实现利奈唑胺耐药,需要更多数据。改进的 LA-XDR MTBC 检测将减少漏报的阻力。
更新日期:2024-12-12
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