Direct from blood identification of bloodstream infections in newborns

项目摘要 新生儿败血症是一种危及生命的疾病，在美国每1,000名活产婴儿中就有2名受到影响。造成 侵入性血流感染（BSI）发生在出生时或出生后不久，疾病的初始阶段 临床表现通常是非特异性的、可变的，有时是微妙的，并且通常是压力的共同迹象。早期 诊断后进行适当的抗菌干预是预后的关键预测因素。选择 适当的抗菌剂受到当前检测和识别BS的诊断过程的限制 都依赖于初级血培养培养是缓慢的，通常需要几天才能产生结果， 由于母体抗生素导致的假阴性在没有诊断确认的情况下，治疗开始于 疑似败血症，使用广谱抗生素。不幸的是，这种策略往往会错过目标， 与副作用有关，包括对发育中的微生物组的损害。因此，至关重要的是 创新的诊断方法，不依赖于培养，以促进准确的诊断， 及时过渡到循证治疗。 为了满足这一未满足的需求，HelixBind开发了RaPID/neo，这是一种全自动的样本到答案测试， 在约3小时内直接从新生儿血液中识别BSI，无需培养。该测试包括一个广泛的测试 18种细菌和真菌病原体构成了新生儿败血症病例的绝大多数。RaPID/neo 在RaPID（耐药性和病原体鉴定）平台上实施，包括一次性测试 试剂卡和台式分析仪。RaPID/neo在其测试菜单中提供单个CFU/ml灵敏度， 未受到多种微生物感染或既往抗菌治疗的混淆。在初步临床试验中， 在评估中，RaPID/neo在整个测定中表现出>92%的灵敏度和99%的特异性。 在这个拟议的直接到第二阶段的项目中，HelixBind将建立在其初步数据的基础上， 通过解决与开发针对这一脆弱群体的测试相关的分析挑战， 患者人群。我们将审查我们的发现和拟议的研究，以获得FDA的监管许可。 在与该机构的预提交过程中。利用机构的反馈，我们将设计一个住院 该研究旨在挑战我们的临床研究计划，为FDA批准的关键试验做准备。 为了在这一奋进中取得成功，我们组建了一个在检测开发方面具有专业知识的成功团队， 仪器仪表、耗材制造、临床微生物学和传染病以及 IVD平台和检测试剂商业化的成功记录。我们将共同努力， 完成产品开发、最终确定监管途径和挑战系统的初步工作 进行了一项住院研究。在这个项目完成后，我们将很好地启动正式的分析 以及FDA批准RaPID/neo的临床研究。

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.