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Development of novel rapid diagnostics for sepsis using the latest nanopore sequencing technologies

使用最新的纳米孔测序技术开发新型脓毒症快速诊断方法

基本信息

批准号：
2283459
负责人：
金额：
--
依托单位：
University of East Anglia
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2283459
关键词：
Development novel rapid diagnostics sepsis

项目摘要

Rapid diagnosis is critical for the effective clinical management of life-threatening infections, especially bloodstream infections (BSI). This is because every hour delay in effective antimicrobial therapy increases risk of mortality by 10%. The gold standard for the diagnosis of BSI is blood culture. However, culture has low sensitivity and a long turnaround time, with results only available 2-5 days after sample collection. Slow diagnostics lead to: 1) poor patient outcomes, 2) the overuse of broad-spectrum antibiotics, which promotes the emergence of antimicrobial resistance (AMR) and 3) increased hospital costs. Nanopore sequencing based clinical metagenomics could replace culture, as it is rapid and can detect any pathogen and AMR gene in a sample.The PhD project aims:1. to develop a metagenomics sequencing-based BSI diagnostic pipeline combining novel pathogen enrichment and host depletion technologies with nanopore sequencing and analysis2. to optimise, evaluate and validate the method on spiked blood samples3. to clinically evaluate the pipeline on blood samples from patients with suspected sepsis/BSI.4. to develop and apply bioinformatic analysis tools that utilise the diagnostic metagenomic data for public health applications, such as hospital infection control and pathogen molecular epidemiology

快速诊断对于危及生命的感染（尤其是血流感染（BSI））的有效临床管理至关重要。这是因为有效抗菌治疗每延迟一小时，死亡风险就会增加 10%。诊断 BSI 的金标准是血培养。然而，培养的灵敏度低，周转时间长，样品采集后 2-5 天才能得出结果。诊断缓慢会导致：1) 患者预后不佳，2) 广谱抗生素的过度使用，从而促进抗菌素耐药性 (AMR) 的出现，3) 医院费用增加。基于纳米孔测序的临床宏基因组学可以取代培养，因为它速度快，可以检测样本中的任何病原体和 AMR 基因。该博士项目的目标：1。开发基于宏基因组测序的 BSI 诊断流程，将新型病原体富集和宿主去除技术与纳米孔测序和分析相结合2。优化、评估和验证加标血液样本的方法3。对疑似脓毒症/BSI患者的血液样本进行管道评估。4。开发和应用生物信息分析工具，利用诊断宏基因组数据进行公共卫生应用，例如医院感染控制和病原体分子流行病学