从脑脊液中进行有针对性的测序,以快速识别耐药结核性脑膜炎
Trinh Thi Bich Tram1, Le Pham Tien Trieu1, Le Thanh Hoang Nhat1
1Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Journal of clinical microbiology
|March 11, 2024
概括
在结核性脑膜炎 (TBM) 中早期检测耐药性至关重要. 针对脑脊液 (CSF) 的下一代测序 (tNGS) 显示出迅速检测TBM耐药性的前景,特别是在细菌负载较高的患者中.
科学领域:
- 传染性疾病 传染性疾病
- 基因组学就是基因组学.
- 微生物学 微生物学
背景情况:
- 结核性脑膜炎 (TBM) 的死亡率很高,由耐药菌株加剧.
- 药物耐药性 (DR) 的早期检测对于改善TBM患者的结果至关重要.
- 目标下一代测序 (tNGS) 提供了高读取深度,用于检测低频DR相关的等位基因.
研究的目的:
- 评估Deeplex Myc-TB tNGS测定用于检测TBM患者药物耐药性的性能.
- 将tNGS基因组药物易感性预测与表型测试和全基因组测序进行比较.
- 评估tNGS结果与TBM临床结果之间的相关性.
主要方法:
- 将Deeplex Myc-TB tNGS测定方法应用于72名已确认TBM的成年人脑脊液 (CSF) 样本.
- 将tNGS基因组药物敏感性预测与复合参考标准 (表型敏感性测试和全基因组测序) 进行比较.
- 分析了与细菌负载,读取深度和临床结果相关的tNGS性能.
主要成果:
- 在33.3%的脊髓样本中,Deeplex检测到Mycobacterium tuberculosis复杂DNA,并为91.7%的阳性样本提供了完整的DR报告.
- 在不考虑低频代基因 (<20%) 时,tNGS与大多数药物的参考标准显示了100%的一致性,除了皮拉津胺和链杆菌素.
- 迪普莱克斯在治疗后具有阳性CSF培养的患者中发现了耐药性,并在一个病例中检测到低频的里法抗性.
结论:
- 在CSF上的tNGS可以快速准确地检测耐药性TBM.
- 目前,tNGS的实用性仅限于脑脊液中细菌负载较高的TBM患者.
- 需要进一步的研究来开发替代的诊断和抗药性检测方法,用于具有较低细菌负担的TBM患者.
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