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

快速诊断对于威胁生命的感染，特别是血液感染的有效临床治疗至关重要。这是因为有效的抗菌治疗每延误一小时，死亡风险就会增加10%。血培养是诊断BSI的金标准。然而，培养法灵敏度低，周转时间长，只有在样本采集后2-5天才能得到结果。诊断缓慢会导致：1)患者预后不佳，2)过度使用广谱抗生素，从而促进抗菌素耐药性(AMR)的出现，3)增加医院费用。基于纳米孔测序的临床元基因组学可以取代培养，因为它快速，可以检测到样本中的任何病原体和AMR基因。博士项目的目标是：1.发展一种基于元基因组测序的BSI诊断流水线，将新的病原体浓缩和宿主枯竭技术与纳米孔测序和分析相结合。对加标血样进行优化、评估和验证。对疑似脓毒症/BSI.3患者的血液样本进行临床评估。开发和应用生物信息学分析工具，将诊断元基因组数据用于公共卫生应用，如医院感染控制和病原体分子流行病学

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