Direct detection and identification of antimicrobial resistance genes in bloodstream infections

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的及时诊断和治疗已被证明有助于改善患者 结果和减少住院时间。然而，目前公认的诊断方法仍然需要 初级血液培养，不仅速度慢，需要大约1-3天，而且还表现出敏感性降低 在进行抗菌治疗的情况下。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。 为了解决这一未得到满足的需求，HelixBind开发了快速(抗药性和病原体鉴定)，一种完全 自动化的样本到答案平台，适合放置在整个医院。RAPID由一个 台式分析仪操作一次性盒式磁带，能够识别和表征复杂的侵袭性 直接来自患者样本的感染，不需要培养。由于没有培养，快速检测不会受到 多菌感染或之前的抗菌治疗。在该平台上实现的第一个测试， RAPID/BSI，结合了21种细菌和真菌病原体的广泛测试菜单，每毫升对单个CFU的敏感性 在大约3个小时内。在多项临床研究中，该测试显示&gt；94%的敏感性和&gt；99%的敏感性。 整个测试菜单中与培养相关的特异性。由于该产品相对于现有替代品的优势 由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 针对在细菌感染中发现的最常见和临床相关的抗菌素耐药性基因。这个测试，RAPID/R， 不仅在抗性基因面板上显示出单一CFU/ml的敏感性，而且还具有 正确描述多重耐药(MDR)微生物的特征。的手动版本已用于 在临床样本中成功检测到耐药性。在这个提议的第二阶段项目中，HelixBind将把 对自动化快速平台进行测试。证明分析敏感性和特异性的研究将是 将完成对快速/R的盲目临床评估。这些研究将确保产品性能 符合规格和临床要求。同时，研究产品验证的设计和 作为提交前流程的一部分，验证将完成并提交给FDA。 为了在这个项目中取得成功，我们组建了一支在化验开发方面具有专业知识的成熟团队， 仪器、耗材制造、法规遵从性、临床微生物学和感染性 疾病。该团队在将FDA批准的IVD平台和检测商业化方面有着成功的记录。 我们将共同努力，在前期工作的基础上完成产品开发。在完成此操作后 通过该项目，我们将能够很好地启动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.