Development of a Novel Whole Genome Sequencing-based Platform for Rapid Identification and Antimicrobial Profiling of Uropathogens

开发基于全基因组测序的新型平台，用于尿路病原体的快速识别和抗菌谱分析

• 批准号: 10382740
• 负责人: Amanda Nicole Billings
• 金额: $ 30.39万
• 依托单位: DAY ZERO DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382740
• 关键词: Address; Advanced Development; Algorithms; Antibiotic Resistance; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Antimicrobial susceptibility; Bacteria; Bacterial DNA; Blood; Blood specimen; Caring; Cells; Cessation of life; Characteristics; Clinical; Collection; Communicable Diseases; Coupled; Cytolysis; DNA; Data; Data Analyses; Data Compromising; Detergents; Development; Diagnosis; Diagnostic; Diagnostic Sensitivity; Economic Burden; Emergency department visit; Ensure; Evidence based treatment; Genomics; Goals; Health; Hospitalization; Hospitals; Hour; Human; Infection; Infective cystitis; Inpatients; Intervention; Length of Stay; Life; Machine Learning; Medical; Membrane; Microbiology; Modification; Molecular; Morbidity - disease rate; Morphology; Multi-Drug Resistance; Nucleotides; Patient Care; Patients; Performance; Phase; Physicians; Preparation; Process; Property; Protocols documentation; Quality of Care; Re 80; Reaction Time; Recovery; Research; Resistance profile; Resolution; Risk; Sampling; Source; Technology; Testing; Time; Urinary tract infection; Urine; Uropathogen; Viscosity; antimicrobial; base; care outcomes; clinically actionable; clinically relevant; cost; cost effective; data quality; design; diagnostic platform; diagnostic tool; diagnostic value; experience; genome sequencing; high risk; human DNA; improved; in-vitro diagnostics; infection management; mortality; nanopore; novel; novel diagnostics; pathogen; pathogenic bacteria; process optimization; research clinical testing; sample collection; standard of care; targeted treatment; validation studies; whole genome

Complicated urinary tract infections are severe or life-threatening infections that extend beyond a simple bladder infection and occur most frequently in hospitalized patients. There are over 2.8 million cases of complicated urinary tract infections in the U.S. each year, with 20% of cases progressing to urosepsis, leading to nearly 150,000 deaths each year. Effective management of complicated urinary tract infections requires the rapid identification of the causative bacterial pathogen(s) and the associated antibiotic resistance profile. The current standard of care, however, is urine culture, which requires 2-3 days from specimen collection until actionable information to guide patient treatment is generated. Hence, there is an urgent need for diagnostic tools that will allow for the rapid identification of uropathogens and their antimicrobial resistance/sensitivity profile(s). To address this unmet need, Day Zero Diagnostics (DZD) is developing a diagnostic workflow that leverages whole genome sequencing and machine learning to deliver high resolution species identification and antimicrobial resistance and susceptibility profiling from a patient sample without the need for urine culture. These data will guide evidence-based treatment decisions to improve patient care. The aims of this proposal are to (1) demonstrate ultra-high enrichment of bacterial DNA from a diverse range of species from urine samples and (2) optimize a sample preparation pipeline to deliver an actionable result in six hours or less, a clinically relevant timeframe for complicated urinary tract infection. The proposed Specific Aims, with quantifiable target metrics, are designed to demonstrate proof-of-concept in advance of the development of a commercial in vitro diagnostic. Upon Phase I completion, Phase II will focus on optimizing the workflow, expanding test capabilities, and analytical and clinical validation studies.

复杂的尿路感染是严重或威胁生命的感染，超出了简单的膀胱 感染，最常发生在住院的患者中。有超过280万例复杂的病例 每年在美国，尿路感染，有20％的病例发展为尿道，几乎导致 每年150,000人死亡。有效管理复杂的尿路感染需要快速 鉴定细菌病原体（S）和相关的抗生素耐药性谱。电流 但是，护理标准是尿培养 产生了指导患者治疗的信息。因此，迫切需要诊断工具 允许快速鉴定尿道病及其抗菌素耐药性/敏感性。到 满足了这个未满足的需求，零天诊断（DZD）正在开发一个利用整体的诊断工作流程 基因组测序和机器学习以提供高分辨率物种鉴定和抗菌剂 不需要尿培养的患者样本的耐药性和敏感性分析。这些数据将 指导基于证据的治疗决策，以改善患者护理。该提议的目的是（1） 展示了来自尿液样品各种物种的细菌DNA的超高富集，（2） 优化样品制备管道以在六个小时或更短时间内提供可操作的结果，临床相关 复杂尿路感染的时间范围。提出的特定目标，具有可量化的目标指标 旨在在商业体外诊断的开发之前证明概念概念。 第一阶段完成后，第二阶段将专注于优化工作流程，扩展测试功能以及 分析和临床验证研究。