An Integrated Device for Rapid Bacteremia Diagnosis Direct from Whole Blood

项目总结 败血症在美国每年导致超过27万人死亡，败血症是对 血流感染(BSI)。BSI的早期诊断和治疗显示患者病情有所改善 结果和减少住院时间。然而，目前被接受的诊断方法还没有 自从自动化血液培养系统问世以来，这一技术有了很大的进步。因此，今天的黄金标准， 不仅反应缓慢，需要大约1-3天，而且在存在抗菌剂的情况下也表现出敏感性降低 治疗。因此，关键是要发展不依赖培养的新诊断方法。 为了解决这一未得到满足的需求，HelixBind开发了RAPID/BSI，这是一种完全自动化的样本到答案测试， 直接从血液中鉴定和鉴定BSI只需约3小时，无需培养。以快速的速度实施 (抗药性和病原体鉴定)平台，适合在医院内放置， RAPID/BSI包含21种细菌和真菌病原体的广泛测试菜单，不会受到之前 抗菌治疗。物种级别的详细信息具有单一CFU/ml的灵敏度，使您能够选择 适当的抗菌剂。RAPID/BSI的商业化将及时提供BSI的特征和 通过有针对性的抗菌治疗进行干预。这将改善患者的预后，并 减少不必要的抗菌剂的使用，减缓抗菌素耐药性的上升。反思 与现有替代方案相比，Rapid/BSI的显著优势以及改善护理和质量的潜力 LIFE，FDA在2020年将RAPID/BSI指定为突破技术。 HelixBind已经达到并超过了第二阶段SBIR中定义的所有具体目标。这包括化验 由台式仪器操作的一次性塑料一次性设备的优化、自动化和测试 临床标本。到目前为止，临床结果显示&gt；94%的灵敏度和99.8%的特异度 超过了我们90%的敏感性和90%的特异性的里程碑。此外，根据潜在客户的反馈， 客户，测试菜单从16种病原体扩大到21种，并具有检测耐药性的能力 对其作用机理进行了论证。 鉴于第二阶段的成功，HelixBind建议在第二阶段B中推动快速/BSI朝着以下目标做好准备 监管许可。具体目标，每个目标都有可量化的交付成果，用于处理FDA的反馈 在提交前会议期间收到，并降低产品制造和可用性方面的风险。 这一拟议的IIB阶段将以一项盲目的、多地点的医院内研究而告终，挑战我们拟议的FDA 重点研究设计。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批准快速/BSI和规模化生产以推出产品的临床研究。

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.