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.

直接在全血上进行血流感染检测 总结 脓毒症是一种危及生命的疾病，由血液中存在的真菌或细菌引起， 1.3在美国，每年有100万人感染败血症。1快速抗菌药物给药对败血症至关重要 然而，目前血流感染诊断的金标准是血培养（BC）， 需要一到五天的时间。5为了向医生提供正确治疗所需的诊断信息， 患者，我们建议开发一个自动化平台，用于快速，广泛和具有成本效益的识别 在没有BC的全血中的微生物。在本建议书中，我们将重点介绍 仪器和第一个检测将直接检测全血真菌。 新平台将基于单分子扫描（SMS），这是一种新型的样品制备和分子检测技术。 在Scanogen开发的检测方法。真菌检测（SMS-Fungi）将检测和识别五种最常见的 引起血液感染的常见念珠菌属以及隐球菌属。证明试剂盒 还利用靶向广泛保守序列的探针来检测整个系统中任何真菌的存在， 血液样本我们的目标是开发一个1小时，准确，广泛，多路复用，全自动化和成本效益 这将有助于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。我们对两者都进行了测试 特异性和广泛的探针与四种常见于血流感染的真菌。我们发现 该测定是高度特异性的，并且具有诊断具有以下症状的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，我们将完成检测的开发 通过包括新的探针和优化整个检测方案（目标1），开发一个beta原型系统 包括自动化仪器和一次性检测盒（Aim 2），并在试验中评价新系统 分析和临床验证研究（目标3）。我们将利用在发展中取得的经验， 目前正在Scanogen开发一种用于结核病护理点检测的快速检测方法， 拥有多学科团队，包括检测开发和仪器开发方面的专家， Becton Dickinson的前工程副总裁，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的分子平台，用于快速分析微生物， 全血，并开发其第一个用于真菌检测的检测方法。如果成功，新的检测方法将大大改善 通过减少诊断延迟和及时开始适当的治疗来管理真菌血症患者 抗真菌治疗