A sample-to-answer diagnostic for neonatal bloodstream infections

新生儿血流感染的样本到答案诊断

• 批准号: 9340504
• 负责人: Alon Singer
• 金额: $ 100.31万
• 依托单位: HELIXBIND, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-18 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9340504
• 关键词: Accounting; Address; Adoption; Affect; Antibiotics; Automation; Bacteria; Birth; Blood; Blood Circulation; Blood Volume; Blood specimen; Chemistry; Clinical; Clinical Microbiology; Clinical Trials; Clinical assessments; Decision Making; Detection; Development; Device Designs; Devices; Diagnosis; Diagnostic; Discrimination; Disease; Evaluation; Freeze Drying; Funding; Hand; High Prevalence; Hospitals; Hour; Human; Infection; Inflammatory Response; Intervention; Lethargies; Life; Liquid substance; Live Birth; Medical center; Microbiology; Modernization; Molecular; Morbidity - disease rate; Neonatal; Neonatal Mortality; Newborn Infant; Nucleic Acids; Onset of illness; Outcome; Pathologist; Pathology; Patients; Performance; Phase; Preparation; Process; Reagent; Sampling; Sensitivity and Specificity; Sepsis; Septicemia; Series; Small Business Innovation Research Grant; Specimen; Speed; Stress; Surface; Symptoms; Testing; Time; Validation; Venous blood sampling; Whole Blood; Work; antimicrobial; assay development; base; combat; commercialization; cost; design; evidence base; experience; fungus; improved outcome; innovation; instrumentation; internal control; microbial; mortality; neonatal sepsis; notch protein; novel; novel strategies; operation; pathogen; prevent

PROJECT SUMMARY Neonatal septicemia is a life-threatening disease that affects roughly 2 out of every 1,000 live births in the US, where 25-30% do not survive. Caused by an infection of the newborn bloodstream either at the time of birth or soon after, the disease’s initial clinical manifestations are often non-specific, variable, at times subtle, and often common to signs of stress. Thus a core requirement to both to rule-in a bloodstream infection (BSI) and to rule- out a BSI is microbiological evidence; which is currently only possible through blood-cultures. Cultures, however, display two major weaknesses which, crucial to outcome, delay the administration of the proper antimicrobials: (1) Long turnaround time of days and (2) high prevalence of false-negative results due to maternal antibiotics and a reduced input blood volume. As time is of essence for optimal outcomes, treatment is generally initiated prior to microbial diagnosis with a cocktail of broad spectrum (i.e. not personalized) antimicrobials, leaving the majority of patients treated inappropriately and those without the disease treated unnecessarily. It is therefore critical to advance innovative diagnostic approaches which do not rely on culturing in order to facilitate a transition to an evidence-based decision making process as soon as feasible. Having met our and exceeded our Phase I Specific Aims, this Phase II proposal focuses on development of a fully-automated neonatal pathogen identification (Neo/PID) platform enabling the ‘hands-free’ identification of the most clinically prevalent pathogens directly from phlebotomy specimens, in roughly 2 hours, without the need to culture. The Phase II proposed diagnostic device is expected to have profound impact, both by improving outcomes by providing a means to develop an evidence driven first-line intervention, and likewise by reducing the use of excessive and unnecessary antimicrobials. In order to succeed in this endeavor, we have assembled a top-notch team including experts in assay development, artificial nucleic acids, and the implementation of automated diagnostics. Additionally, we have enlisted key advisors in clinical microbiology, surface chemistry, and pathology as well as successful entrepreneurs experienced in the commercialization of diagnostic devices. Together, we will build upon our impressive Phase I results and develop an automated platform, dedicated to neonatal BSIs, culminating in a performance assessment study with clinical specimens. Having achieved our Specific Aims, we will develop deployable instrumentation/consumables and validate our diagnostic in preparation for the pivotal clinical trial.

项目摘要 新生儿败血病是一种威胁生命的疾病，在美国每1000名活产中约有2个 其中25-30％无法生存。由新生儿血液感染在出生时或 不久之后，该疾病的最初临床表现通常是非特异性的，可变的，有时是微妙的，而且通常是 压力迹象共有。既要统治血液感染（BSI）和统治的核心要求 BSI是微生物学证据。目前只有通过血液培养才有可能。文化， 但是，显示两个主要弱点，对于结果至关重要，延迟了适当的管理 抗微生物：（1）几天的漫长周转时间和（2）由于假阴性结果的高流行率 母体抗生素和输入血容量减少。由于时间是最佳结果的本质，因此治疗 通常在微生物诊断之前开始使用广阔的鸡尾酒（即未个性化）启动 抗菌药物，使大多数患者不适当地治疗患者，没有疾病治疗的患者 不必要。因此，进步不依赖的创新诊断方法至关重要 培养以促进可行的过渡到基于证据的决策过程。 达到了我们的并超过了我们的I阶段特定目标，该第二阶段提案着重于开发 完全自动的新生儿病原体鉴定（NEO/PID）平台实现“免提”识别 在大约2小时内，直接来自静脉切开术标本中最普遍的病原体，没有 需要文化。 II期提议的诊断装置有望产生深远的影响，既可以 通过提供一种开发证据推动一线干预的手段来改善结果，同样 通过减少过量和不必要的抗菌药物的使用。 为了在这项工作中取得成功，我们组建了一支顶级团队，包括分析专家 开发，人造核酸以及自动诊断的实施。另外，我们还有 临床微生物学，表面化学和病理学以及成功的关键顾问 企业家在诊断设备的商业化方面经验丰富。一起，我们将建立在我们的基础上 令人印象深刻的第一阶段结果并开发了一个专门用于新生儿BSI的自动化平台，最终达到 绩效评估研究具有临床规格。达到了我们的具体目标后，我们将发展 可部署的仪器/消耗品，并验证我们的诊断以准备关键临床 审判。