Direct detection and identification of antimicrobial resistance genes in bloodstream infections

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）。已证明及时诊断和治疗BSI可改善患者 结果，减少住院时间。然而，目前公认的诊断方法仍然需要 原代血培养，不仅速度慢，需要约1-3天，而且灵敏度降低 在抗菌处理的存在下。因此，非常需要新的诊断方法， 不需要培养，并提供更快，更准确的结果。 为了解决这一未满足的需求，HelixBind开发了RaPID（抗性和病原体鉴定），这是一个完全的 自动化的样品到答案平台，适合在整个医院放置。RaPID由一个 台式分析仪操作一次性试剂卡，能够识别和表征复杂的侵入性 直接从患者标本中感染，无需培养。由于无培养物，RaPID检测不受 多种微生物感染，也没有接受过抗菌治疗。在这个平台上实施的第一个测试， RaPID/BSI包含21种细菌和真菌病原体的广泛检测菜单，具有单一CFU/ml灵敏度 大约3小时内。在多项临床研究中，该测试已证明>94%的灵敏度和>99%的敏感性。 在整个测试菜单中相对于文化的特异性。由于该产品优于现有替代品， 鉴于其改善护理的潜力，FDA在2020年将RaPID/BSI指定为突破性技术。 HelixBind最近完成了反射测试的概念验证研究，以补充RaPID/BSI， 靶向BSI中发现的最常见和临床相关的抗菌素耐药基因。这个测试，RaPID/R， 不仅证明了在抗性基因组中的单个CFU/ml敏感性，而且还证明了 正确表征多重耐药（MDR）微生物。的手动版本已用于 成功检测临床样本中的耐药性。在这个拟议的第二阶段项目中，HelixBind将翻译 测试自动化RaPID平台。将开展证明分析灵敏度和特异性的研究， 完成RaPID/R的盲态临床评估。这些研究将确保产品性能 符合规范和临床要求。同时，研究产品验证设计， 将完成验证并作为预提交流程的一部分提交给FDA。 为了在这个项目中取得成功，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、耗材制造、法规合规性、临床微生物学和感染性 疾病该团队在FDA批准的IVD平台和检测试剂盒的商业化方面有着成功的记录。 我们将在前期工作的基础上共同完成产品开发。在完成此 项目，我们将很好地启动FDA批准所需的正式分析和临床研究。

PROJECT SUMMARY Leading to over 270,000 deaths in the US annually, septicemia is the systemic inflammatory response to a bloodstream infection (BSI). Timely diagnosis and treatment of BSIs has been demonstrated to improve patient outcomes and reduce hospitalization time. However, currently accepted diagnostic approaches still require primary blood cultures, which are not only slow, requiring ~1-3 days, but also demonstrate reduced sensitivity in the presence of antimicrobial treatment. There is thus a significant need for new diagnostic approaches that do not require cultures and provide faster, more accurate results. To address this unmet need, HelixBind developed RaPID (Resistance and Pathogen IDentification), a fully automated, sample-to-answer platform appropriate for placement throughout the hospital. RaPID consists of a bench-top Analyzer operating single-use cassettes capable of identifying and characterizing complex invasive infections directly from patient specimens, without cultures. Being culture-free, RaPID tests are not inhibited by polymicrobial infections nor prior antimicrobial treatment. The first test implemented on this platform, RaPID/BSI, incorporates a broad test menu of 21 bacterial and fungal pathogens with single CFUs/ml sensitivity within roughly 3 hours. Over multiple clinical studies the test has demonstrated >94% sensitivity and >99% specificity relative to culture across the test menu. Owing to the product’s advantages over exiting alternatives and its potential to improve care, the FDA designated RaPID/BSI a Breakthrough Technology in 2020. HelixBind has recently completed proof-of-concept studies of a reflex test to complement RaPID/BSI which targets the most common and clinically relevant antimicrobial resistance genes found in BSIs. This test, RaPID/R, has not only demonstrated single CFUs/ml sensitivity across the panel of resistance genes, but also the ability to properly characterize multiple drug resistant (MDR) microorganisms. A manual version of the has been used to successfully detect resistance in clinical samples. In this proposed Phase II project, HelixBind will translate the test to the automated RaPID platform. Studies demonstrating analytical sensitivity and specificity will be completed as will a blinded clinical assessment of RaPID/R. These studies will ensure that product performance matches specifications and clinical requirements. In parallel, study designs for product verification and validation will be completed and submitted to the FDA as part of a Pre-Submission process. To succeed in this project, we have assembled an accomplished team with expertise in assay development, instrumentation, consumables manufacturing, regulatory compliance, clinical microbiology, and infectious disease. This team has a successful track record of commercializing FDA-cleared IVD platforms and assays. Together, we will build upon our preliminary work to complete product development. Upon completion of this project, we will be well placed to initiate formal Analytical and Clinical studies required for FDA clearance.