Rapid identification of a Mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum
Rapid identification of a Mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum
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DOI：
10.1016/j.ijid.2017.07.007
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发表时间：
2017-09-01
影响因子：
8.4
通讯作者：
Breuer, Judith
中科院分区：
文献类型：
--
作者：
Nimmo, Camus;Doyle, Ronan;Breuer, Judith
简介：对二线结核病药物的耐药性很常见，但通过表型药物敏感性测试诊断缓慢。快速分子检测可以加快诊断速度，但只能检测有限的突变。培养分离株的全基因组测序 (WGS) 可以生成完整的遗传耐药谱，但会因初始培养步骤而延迟。在此介绍的案例中，通过定向浓缩成功实现了直接从痰液中进行全基因组测序。案例报告：一名 29 岁的尼日利亚妇女被诊断患有肺结核。 Xpert MTB/RIF 和 Hain 线探针检测鉴定出 rpoB 和 inhA 突变与利福平和中间异烟肼耐药一致，以及进一步可能的突变赋予氟喹诺酮耐药。直接从痰中进行的全基因组测序鉴定出与高水平异烟肼耐药性一致的进一步 inhA 突变，并证实不存在氟喹诺酮耐药性。停用异烟肼，患者完成了 18 个月的氟喹诺酮类治疗方案，未出现复发。讨论：与快速分子检测（只能检查有限数量的突变）和培养分离物的全基因组测序（需要培养步骤）相比，直接从痰液中进行全基因组测序可以快速生成完整的遗传耐药谱。在这种情况下，全基因组测序改变了耐药结核病的临床管理，并证明了在二线耐药性常见的情况下指导个体化药物治疗的潜力。 (C) 2017 年作者。由爱思唯尔有限公司代表国际传染病学会出版。
Introduction: Resistance to second-line tuberculosis drugs is common, but slow to diagnose with phenotypic drug sensitivity testing. Rapid molecular tests speed up diagnosis, but can only detect limited mutations. Whole genome sequencing (WGS) of culture isolates can generate a complete genetic drug resistance profile, but is delayed by the initial culture step. In the case presented here, successful WGS directly from sputum was achieved using targeted enrichment.Case report: A 29-year-old Nigerian woman was diagnosed with tuberculosis. Xpert MTB/RIF and Hain line probe assays identified rpoB and inhA mutations consistent with rifampicin and intermediate isoniazid resistance, and a further possible mutation conferring fluoroquinolone resistance. WGS directly from sputum identified a further inhA mutation consistent with high-level isoniazid resistance and confirmed the absence of fluoroquinolone resistance. Isoniazid was stopped, and the patient has completed 18 months of a fluoroquinolone-based regimen without relapse.Discussion: Compared to rapid molecular tests (which can only examine a limited number of mutations) and WGS of culture isolates (which requires a culture step), WGS directly from sputum can quickly generate a complete genetic drug resistance profile. In this case, WGS altered the clinical management of drug-resistant tuberculosis and demonstrated potential for guiding individualized drug treatment where second-line drug resistance is common. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.