An Integrated Device for Rapid Bacteremia Diagnosis Direct from Whole Blood

项目摘要 败血症每年在美国导致超过270，000人死亡，败血症是对急性炎症的全身性炎症反应。 血液感染（BSI）。BSI的早期诊断和治疗已证明患者 结果和减少住院时间。然而，目前公认的诊断方法还没有 自自动化血液培养系统出现以来，因此，今天的金本位制， 不仅缓慢，需要约1-3天，而且在抗菌剂存在下显示出降低的敏感性。 治疗因此，推进不依赖于培养的新诊断方法至关重要。 为了解决这一未满足的需求，HelixBind开发了RaPID/BSI，这是一种全自动的样本到答案测试， 在约3小时内直接从血液中识别和表征BSI，无需培养。在RaPID上实施 （耐药性和病原体鉴定）平台，并适合在整个医院放置， RaPID/BSI包含了21种细菌和真菌病原体的广泛测试菜单，并且不会受到先前测试的影响。 抗菌处理提供了单个CFU/ml灵敏度的种属级别详细信息， 适当的抗菌剂。RaPID/BSI的商业化将提供BSI的及时表征， 使干预与有针对性的抗菌治疗。这将改善患者的预后， 减少不必要的抗菌药物的使用，减缓抗菌药物耐药性的上升。反映 RaPID/BSI相对于现有替代品的显著优势以及改善护理和质量的潜力 FDA在2020年将RaPID/BSI指定为突破性技术。 HelixBind已经达到并超过了第二阶段SBIR中定义的所有具体目标。这包括含量测定 优化，自动化到由台式仪器操作的一次性塑料上，并测试 临床标本临床结果表明，整个检测试剂盒的灵敏度>94%，特异性> 99.8%， 超过了我们90%灵敏度和90%特异性的里程碑此外，根据潜在客户的反馈， 客户，测试菜单从16个扩大到21个病原体和检测耐药性的能力 机制得到证实。 鉴于第二阶段的成功，HelixBind在第二B阶段建议将RaPID/BSI推向准备就绪， 监管许可。具体目标，每个目标都有可量化的可交付成果，用于解决FDA的反馈 提交前会议期间收到的信息，并对产品的制造和可用性方面进行风险消除。 这项拟议的IIB期研究将以一项设盲、多中心院内研究为高潮，挑战我们拟议的FDA 关键研究设计。在这个项目完成后，我们将很好地启动正式的分析和 FDA批准RaPID/BSI的临床研究和产品上市的规模生产。

PROJECT SUMMARY Leading to over 270,000 deaths in the US annually, septicemia is the systemic inflammatory response to a bloodstream infection (BSI). Early diagnosis and treatment of BSIs have demonstrated improved patient outcomes and reduced hospitalization time. However, currently accepted diagnostic approaches have not advanced substantially since the advent of automated blood culturing systems. As such, today’s gold-standard, is not only slow, requiring ~1-3 days, but also demonstrates reduced sensitivity in the presence of antimicrobial treatment. It is therefore critical to advance new diagnostic approaches, which do not rely on culturing. To address this unmet need, HelixBind developed RaPID/BSI, a fully automated sample-to-answer test which identifies and characterizes BSIs directly from blood in ~3 hours, without cultures. Implemented on the RaPID (Resistance and Pathogen IDentification) platform and appropriate for placement throughout the hospital, RaPID/BSI incorporates a broad test menu of 21 bacterial and fungal pathogens and is not compromised by prior antimicrobial treatment. Species level detail is provided with single CFUs/ml sensitivity, enabling selection of appropriate antimicrobials. Commercialization of RaPID/BSI would provide timely characterization of BSIs and enable intervention with targeted antimicrobial treatment. This would result in improved patient outcomes and a reduction in the use of unnecessary antimicrobials, slowing the rise of antimicrobial resistance. Reflecting RaPID/BSI’s significant advantages over exiting alternatives and the potential to improve care and quality of life, the FDA designated RaPID/BSI a Breakthrough Technology in 2020. HelixBind has met and exceeded all of the Specific Aims defined in the Phase II SBIR. This included assay optimization, automation onto a single-use plastic disposable operated by a benchtop instrument, and testing of clinical specimens. Clinical results demonstrating >94% sensitivity and 99.8% specificity across the assay far surpassed our milestone of 90% sensitivity and 90% specificity. In addition, based on feedback from potential customers, the test menu was expanded from 16 to 21 pathogens and the capability to detect resistance mechanisms was demonstrated. Given the success of Phase II, HelixBind proposes in Phase IIB to advance RaPID/BSI toward readiness for regulatory clearance. Specific Aims, each with quantifiable deliverables, serve to address feedback form FDA received during a Pre-Submission meeting and to de-risk manufacturing and usability aspects of the product. This proposed Phase IIB will culminate in a blinded, multi-site in-hospital study, challenging our proposed FDA pivotal study design. Upon completion of this project, we will be well placed to initiate formal Analytical and Clinical studies for FDA clearance of RaPID/BSI and scale manufacturing for product launch.