Bloodstream infection detection directly on whole blood

直接对全血进行血流感染检测

• 批准号: 9908875
• 负责人: Alfredo Andres Celedon
• 金额: $ 100万
• 依托单位: SCANOGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908875
• 关键词: Affect; Anti-Bacterial Agents; Antifungal Agents; Antifungal Therapy; Bacteria; Biological Assay; Blood; Blood Circulation; Blood specimen; Candida; Clinical; Clinical Research; Conserved Sequence; Cryptococcus; Detection; Development; Device or Instrument Development; Diagnosis; Diagnostic; Diagnostic Procedure; Engineering; Fungemia; Goals; Gold; Hospitals; Hour; Laboratories; Life; Methods; Microbiology; Molecular; Mycoses; Nucleic Acid Hybridization; Patients; Performance; Phase; Physicians; Pilot Projects; Predisposition; Preparation; Price; Protocols documentation; Resources; Ribosomal RNA; Sampling; Scanning; Sepsis; System; Techniques; Technology; Testing; Time; Tuberculosis; United States; United States Food and Drug Administration; Universities; Validation; Whole Blood; Work; antimicrobial; assay development; base; candidemia; clinical Diagnosis; cost effective; experience; fungus; improved; instrument; manufacturability; microorganism; mortality; multidisciplinary; novel; pathogen; point of care; protocol development; prototype; rapid detection; single molecule; usability; validation studies

Bloodstream infection detection directly on whole blood Summary Sepsis is a life-threatening condition triggered by the presence of fungi or bacteria in the bloodstream that affects 1.3 million people each year in the United States.1 Rapid antimicrobial administration is critical for sepsis treatment.2-4 However, the current gold standard for bloodstream infection diagnosis is blood culture (BC), which takes one to five days.5 In order to provide physicians with the needed diagnostic information to properly treat patients, we propose the development of an automated platform for rapid, broad and cost-effective identification of microorganisms in whole-blood without BC. In this proposal, we will focus on the development of the instrument and the first assay which will detect fungi directly on whole-blood. The new platform will be based on Single Molecule Scanning (SMS), a novel sample preparation and molecular detection method developed at Scanogen. The fungi assay (SMS-Fungi) will detect and identify the five most common Candida species that cause bloodstream infections as well as the Cryptococcus genus. The assay will also utilize probes that target broadly conserved sequences to detect the presence of any fungi in the whole- blood specimen. The goal is to develop a 1-hour, accurate, broad, multiplexed, fully-automated and cost-effective assay, that will aid physicians to start proper antifungal therapy without delay. In phase I, we developed an assay protocol capable of detecting fungi directly in whole-blood. We tested both specific and broad-range probes with four species of fungi commonly found in bloodstream infections. We found that the assay is highly specific and has the high sensitivity required for the diagnosis of clinical cases with a limit of detection (LOD) as low as 1 CFU/ml. In this project, we will complete the development of the assay protocol by including new probes and optimizing the overall assay (Aim 1), develop a beta-prototype system consisting of an automated instrument and disposable cartridge (Aim 2) and evaluate the new system in pilot analytical and clinical validation studies (Aim 3). We will leverage the experience attained in the development of a rapid assay for point of care detection of Tuberculosis currently under development at Scanogen, and work with a multidisciplinary team that includes experts in assay development and instrument development including the former Vice President of Engineering at Becton Dickinson, experts in fungal infection diagnosis and treatment from Johns Hopkins University and engineers from Key Technologies. Our goal is to develop and validate an automated molecular platform for rapid analysis of microorganisms in whole-blood and develop its first assay for fungi detection. If successful, the new assay will dramatically improve the management of patients with fungemia by reducing diagnostic delay and enabling timely initiation of proper antifungal treatment.

直接对全血进行血流感染检测 概括 败血症是一种危及生命的疾病，由血液中存在真菌或细菌引发，影响 美国每年有 130 万人。1 快速抗菌药物治疗对于脓毒症至关重要 治疗。2-4 然而，目前血流感染诊断的金标准是血培养（BC）， 需要一到五天。5为了向医生提供正确治疗所需的诊断信息 对于患者，我们建议开发一个自动化平台，以实现快速、广泛且经济高效的识别 不含 BC 的全血中微生物的数量。在本提案中，我们将重点关注 仪器和第一个直接检测全血真菌的检测方法。 新平台将基于单分子扫描（SMS），这是一种新颖的样品制备和分子扫描技术 Scanogen 开发的检测方法。真菌检测（SMS-Fungi）将检测并识别最常见的五种真菌。 引起血液感染的常见念珠菌属以及隐球菌属。该测定将 还利用针对广泛保守序列的探针来检测整个过程中是否存在任何真菌 血液标本。目标是开发一个1小时、准确、广泛、多路复用、全自动且具有成本效益的 检测，这将帮助医生立即开始适当的抗真菌治疗。 在第一阶段，我们开发了一种能够直接检测全血中真菌的检测方案。我们测试了两者 对血液感染中常见的四种真菌进行特异性和广泛的探针。我们发现 该检测具有高度特异性，并且具有诊断临床病例所需的高灵敏度 检测限 (LOD) 低至 1 CFU/ml。在这个项目中，我们将完成检测方法的开发 通过包含新探针和优化整体测定（目标 1）的方案，开发 beta 原型系统 由自动化仪器和一次性试剂盒组成（目标 2），并在试点中评估新系统 分析和临床验证研究（目标 3）。我们将利用在开发过程中获得的经验 Scanogen 目前正在开发一种快速床边检测结核病的方法，并正在开展工作 拥有一支多学科团队，其中包括分析开发和仪器开发方面的专家，包括 前碧迪公司工程副总裁，真菌感染诊断和治疗专家 来自约翰霍普金斯大学和关键技术公司的工程师。 我们的目标是开发和验证一个自动化分子平台，用于快速分析微生物 全血并开发出第一个真菌检测方法。如果成功，新的检测方法将显着改善 通过减少诊断延迟和及时启动适当的治疗来管理真菌血症患者 抗真菌治疗。