Direct from blood identification of bloodstream infections in newborns

直接从血液中鉴定新生儿血流感染

• 批准号: 10477151
• 负责人: Alon Singer
• 金额: $ 99.46万
• 依托单位: HELIXBIND, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10477151
• 关键词: Accounting; Address; Adopted; Adult; Affect; Antibiotics; Antimicrobial Resistance; Biological Assay; Birth; Blood; Blood Volume; Blood specimen; Budgets; Chicago; Childhood; Clinic; Clinical; Clinical Microbiology; Clinical Research; Clinical assessments; Communicable Diseases; DNA sequencing; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Equipment; Diagnostic tests; Disease; Early Diagnosis; Ensure; Etiology; Evidence based treatment; Exhibits; Feedback; Hospitals; Hour; Infection; Intervention; Laboratories; Life; Live Birth; Medical center; Methods; Molecular; Morbidity - disease rate; Neonatal Mortality; Newborn Infant; Outcome; Patients; Pediatric Hospitals; Performance; Phase; Population; Positioning Attribute; Preparation; Process; Regulatory Pathway; Resistance; Risk; Sampling; Sensitivity and Specificity; Sepsis; Specificity; Stress; System; Technology; Temperature; Testing; Time; TimeLine; University Hospitals; Whole Blood; Work; accurate diagnosis; antimicrobial; assay development; base; cost; cross reactivity; design; diagnostic assay; diagnostic platform; diagnostic strategy; experience; in-vitro diagnostics; innovation; instrument; instrumentation; intrapartum; manufacturing scale-up; meetings; member; microbial; microbiome; mortality; neonatal sepsis; neonate; outcome prediction; pathogen; pathogenic bacteria; pathogenic fungus; patient population; performance tests; product development; programs; resistance gene; side effect; success; systemic inflammatory response

PROJECT SUMMARY Neonatal sepsis is a life-threatening disease that affects 2 out of every 1,000 live births in the US. Caused by an invasive bloodstream infection (BSI) occurring either at the time of birth or soon thereafter, the disease’s initial clinical manifestations are often non-specific, variable, at times subtle, and often common to signs of stress. Early diagnosis followed by appropriate antimicrobial intervention is a key predictor of outcomes. Selection of appropriate antimicrobials is limited by the current diagnostic process for detection and identification of BSIs which all rely on primary blood cultures. Cultures are slow, often requiring days to yield a result, and prone to false-negatives due to maternal antibiotics. In the absence of diagnostic confirmation, treatment is initiated upon suspicion of sepsis with broad spectrum antibiotics. Unfortunately, this strategy often misses the target and is associated with side effects, including damage to developing microbiomes. It is therefore critical to advance innovative diagnostic approaches which do not rely on culturing in order to facilitate accurate diagnosis and timely transition to evidence-based treatments. To address this unmet need, HelixBind developed RaPID/neo, a fully automated, sample-to-answer test for identifying BSIs directly from newborn blood within ~3 hours, without cultures. The test incorporates a broad test menu of 18 bacterial and fungal pathogens that make up the vast majority of neonatal sepsis cases. RaPID/neo is implemented on the RaPID (Resistance and Pathogen IDentification) platform, incorporating single-use test cassettes and a bench top Analyzer. RaPID/neo provides single CFUs/ml sensitivity across its test menu and is not confounded by polymicrobial infections nor prior antimicrobial treatment. In a preliminary clinical assessment, RaPID/neo demonstrated >92% sensitivity and 99% specificity across the assay. In this proposed Direct-to-Phase II project, HelixBind will build on its preliminary data to further product development by addressing analytical challenges associated with developing a test targeting this vulnerable patient population. We will review our findings and proposed studies for regulatory clearance with the FDA during a Pre-Submission process with the agency. Leveraging agency feedback, we will design an in-hospital study aimed at challenging our clinical studies plan in preparation for the pivotal trials for FDA clearance. To succeed in this endeavor, we have assembled an accomplished team with expertise in assay development, instrumentation, consumables manufacturing, clinical microbiology, and infectious disease as well as a successful track record of commercializing IVD platforms and assays. Together, we will build upon our preliminary work to complete product development, finalize a regulatory pathway, and challenge the system with an in-hospital study. Upon completion of this project, we will be well placed to initiate formal Analytical and Clinical studies for FDA clearance of RaPID/neo.

项目摘要 新生儿败血症是一种威胁生命的疾病，在美国每1000名活产中有2个。由An引起 侵入性血液感染（BSI）发生在出生时或此后不久，该疾病的初始 临床表现通常是非特异性的，可变的，有时是微妙的，并且通常是压力迹象。早期的 诊断和适当的抗菌干预是结果的关键预测指标。选择 适当的抗微生物受到当前检测和鉴定的诊断过程的限制 所有这些都依赖原发性血液培养。培养很慢，通常需要几天才能产生结果，并且容易 由于母体抗生素而导致的假阴性。在没有诊断确认的情况下，开始治疗 具有广谱抗生素的败血症的可疑。不幸的是，这种策略通常会错过目标，并且是 与副作用相关，包括损害发育中的微生物组。因此，进步至关重要 为了促进准确的诊断和 及时过渡到基于证据的治疗。 为了满足这种未满足的需求，HelixBind开发了快速/NEO，这是一种全自动的样本到答案测试 在〜3小时内直接从新生儿识别BSI，而无需培养。该测试包含广泛的测试 构成绝大多数新生儿败血症病例的18种细菌和真菌病原体的菜单。快速/neo 在快速（电阻和病原体识别）平台上实现，并包含一次性测试 录音带和台式分析仪。 Rapid/Neo在其测试菜单上提供单个CFU/ML灵敏度，IS 多数菌感染或先前的抗菌治疗不会混淆。在初步临床中 评估，快速/NEO在整个测定中表现出> 92％的敏感性和99％的特异性。 在此拟议的直接到相之间II项目中，HelixBind将基于其初步数据以进一步的产品 通过应对与针对这种脆弱的测试相关的分析挑战来开发 患者人数。我们将回顾我们的发现和提议的研究，以通过FDA进行监管清除 在与该机构进行的提交过程中。利用代理商的反馈，我们将设计住院 旨在挑战我们的临床研究计划的研究，为FDA清除的关键试验做准备。 为了在这项努力中取得成功，我们组建了一支成就卓著的团队，具有分析开发方面的专业知识， 仪器，消耗品制造，临床微生物学和传染病以及 商业化IVD平台和测定的成功记录。一起，我们将建立在我们的基础上 初步工作以完成产品开发，确定监管途径并挑战系统 进行院内研究。该项目完成后，我们将很适合发起正式的分析 和FDA清除快速/NEO的临床研究。