Direct from blood identification of bloodstream infections in newborns

项目总结 新生儿败血症是一种威胁生命的疾病，在美国每1000名活产中就有2名受到影响。由一种 侵袭性血流感染(BSI)发生在出生时或出生后不久，疾病的初始 临床表现通常是非特异性的，多变的，有时微妙的，通常是应激的迹象。早些时候 诊断后进行适当的抗微生物干预是预测结果的关键因素。精选 适当的抗菌剂受到目前检测和鉴定细菌感染的诊断程序的限制 它们都依赖于初级血液培养。培养是缓慢的，通常需要几天才能产生结果，而且容易 假阴性--由母体抗生素引起。在没有诊断确认的情况下，开始治疗 怀疑败血症使用广谱抗生素。不幸的是，这一战略经常没有达到目标，而且 与副作用有关，包括对发育中的微生物的损害。因此，前进是至关重要的 创新的诊断方法，不依赖培养，以促进准确的诊断和 及时过渡到循证治疗。 为了解决这一未得到满足的需求，HelixBind开发了Rapid/neo，这是一种完全自动化的、样本到答案的测试 在~3小时内直接从新生儿血液中鉴定细菌感染，无需培养。这项测试包含了一项广泛的测试 名单上的18种细菌和真菌病原体构成了新生儿败血症的绝大多数。快速/近地天体 是在快速(抗性和病原体鉴定)平台上实施的，包含一次性测试 盒式磁带和一台台式分析仪。Rapid/neo在其测试菜单中提供单CFU/ml灵敏度，并且 没有受到多菌感染的困扰，也没有接受过抗菌治疗。在初步的临床试验中 评估，快速/NEO在整个检测中显示了92%的敏感性和99%的特异性。 在这个提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，以进一步生产 通过解决与开发针对此漏洞的测试相关的分析挑战来进行开发 病人群体。我们将审查我们的发现和拟议的研究，以获得FDA的监管批准 在与该机构的提交前过程中。利用机构的反馈，我们将设计一种住院 这项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。 为了在这项工作中取得成功，我们组建了一支在分析开发方面具有专业知识的成熟团队， 仪器仪表、耗材制造、临床微生物学和传染病以及 IVD平台和化验商业化的成功记录。共同努力，我们将在我们的 完成产品开发的前期工作，最终确定监管途径，并挑战系统 有一项住院研究。在这个项目完成后，我们将处于有利地位，启动正式的分析 和FDA清除快速/近视的临床研究。

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.