基于线探针检测的分子检测对利福平耐药结核病患者个体化治疗的影响：来自乌克兰前瞻性 INNOVA4TB 队列研究的数据。
Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.
机构信息
Department of Tuberculosis, Clinical Immunology and Allergy, National Pirogov Memorial Medical University, 56 Pyrogova St., Vinnytsia 21018, Ukraine.
Institut d'Investigació Germans Trias i Pujol (IGTP), Mar Building, P1-18, Carretera de Can Ruti, Camí de les Escoles s/n, Badalona 08916, Barcelona, Spain.
出版信息
Ther Adv Respir Dis. 2024 Jan-Dec;18:17534666241249841. doi: 10.1177/17534666241249841.
BACKGROUND
Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together.
OBJECTIVES
The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens.
DESIGN
A prospective observational cohort study.
METHODS
From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine.
RESULTS
A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens ( < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine.
CONCLUSION
Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.
背景
乌克兰仍然是世界卫生组织对抗耐药结核病（TB）的高度优先国家。利福平耐药结核病（RR-TB）的治疗时间更长、更复杂且费用更高。2021 年，乌克兰报告了 4025 例 RR-TB 病例，比所有 30 个欧盟/欧洲经济区国家加起来的病例（751 例）多 5.4 倍。
目的
本研究旨在确定线探针分析（LPA）对检测抗结核药物耐药性的诊断准确性，并评估其在选择治疗方案中的临床应用。
设计
前瞻性观察队列研究。
方法
2019 年 5 月至 2020 年 6 月，我们连续纳入了在乌克兰文尼察地区肺病和胸部外科中心住院的活动性结核病患者（年龄 18 至 82 岁）。LPA 在乌克兰文尼察国家皮罗戈夫纪念医学大学的遗传研究实验室进行。
结果
在研究期间，共对 126 例结核病患者的 84 份临床标本和 97 份培养分离物进行了检测。与表型药物敏感性试验（DST）相比，LPA 对临床标本的准确性（95%置信区间）为异烟肼（H）80.1（68.5-89.0）、利福平（R）74.7（62.4-84.6）、乙胺丁醇 74.4（62.5-84.1）、链霉素 71.4（41.9-91.6）、丙硫异烟胺/乙硫异烟胺 84.6（62.4-96.5）和左氧氟沙星（Lfx）84.6（73.6-92.3）。我们发现 LPA 对培养分离物中 H、R 和 Lfx 的检测灵敏度明显高于临床标本（<0.05）。LPA 在 17 例对 R 敏感的患者中发现了 6 例（35.5%）Xpert 检测未发现的突变。在乌克兰 RR-TB 患者队列中，注射用药物的较短治疗方案的适宜率仅为 5%（8/156）。
结论
初步 LPA 检测可准确识别抗结核药物耐药性，并有助于选择合适的治疗方案，最大限度减少经验性治疗的暴露。
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