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液感染检测 概括 败血症是一种威胁生命的疾病，该疾病是由影响的血液中的真菌或细菌触发的 1美国每年有130万人。1快速抗菌剂对败血症至关重要 2-4然而，当前的血液感染诊断金标准是血液培养（BC），它 花一到五天。5为了向医生提供所需的诊断信息以正确治疗 患者，我们建议开发一个自动化平台，以快速，广泛和成本效益 没有卑诗省的全血中的微生物。在此提案中，我们将专注于 仪器和第一个将直接在全血上检测真菌的测定法。 新平台将基于单分子扫描（SMS），这是一种新型样品制备和分子 在扫描原开发的检测方法。真菌分析（SMS-fungi）将检测并确定五个 引起血液感染以及加密型属的常见念珠菌物种。测定法 还利用靶向广泛保守序列的探针来检测整个真菌的存在 血标本。目的是开发1小时，准确，宽，多路复用，完全自动化和成本效益 测定，这将有助于医生立即开始适当的抗真菌疗法。 在第一阶段，我们开发了一种能够直接在全血中检测真菌的测定方案。我们两者都测试了 特定且宽范围的探针在血液感染中常见于四种真菌。我们发现 该测定具有很高的特异性，并且具有诊断为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，我们将完成测定的开发 通过包括新的探针并优化整体测定（AIM 1），开发Beta-Prototype系统来协议 由自动仪器和一次性弹药筒组成（AIM 2）并评估飞行员的新系统 分析和临床验证研究（AIM 3）。我们将利用在开发中获得的经验 用于目前正在扫描原开发的结核病的护理点检测的快速测定，并起作用 与包括分析开发和仪器开发专家在内的多学科团队，包括 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的工程师。 我们的目标是开发和验证自动分子平台，以快速分析微生物中的微生物 全血，并开发出第一个用于真菌检测的测定法。如果成功，新测定将显着改善 通过减少诊断延迟并及时启动适当的真菌患者的管理 抗真菌治疗。