Direct detection and identification of antimicrobial resistance genes in bloodstream infections

血流感染中抗菌药物耐药基因的直接检测和鉴定

• 批准号: 10680500
• 负责人: Alon Singer
• 金额: $ 100万
• 依托单位: HELIXBIND, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-09 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680500
• 关键词: Address; Adopted; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Bacteremia; Biological Assay; Blinded; Blood; Blood specimen; Breakthrough device; Budgets; Caring; Cessation of life; Clinic; Clinical; Clinical Microbiology; Clinical Research; Clinical assessments; Communicable Diseases; Complement; Complex; Detection; Deterioration; Development; Diagnosis; Diagnostic; Diagnostic Equipment; Engineering; Ensure; Health system; Hospitalization; Hospitals; Hour; Infection; Laboratories; Lead; Life; Manuals; Marketing; Medical center; Methods; Molecular; Multi-Drug Resistance; Patient-Focused Outcomes; Patients; Performance; Phase; Physicians; Play; Preparation; Process; Reflex action; Research Design; Resistance; Resistance development; Risk; Role; Sampling; Sensitivity and Specificity; Sepsis; Septicemia; Specific qualifier value; Specificity; Specimen; Technology; Temperature; Testing; Time; Translating; University Hospitals; Whole Blood; Work; antimicrobial; assay development; clinically relevant; commercialization; cost; cross reactivity; design; diagnostic strategy; drug resistant microorganism; experience; improved; instrument; instrumentation; manufacture; member; microbial; mortality; novel; novel diagnostics; pathogen; pathogenic bacteria; pathogenic fungus; patient prognosis; product development; programs; resistance gene; resistance mechanism; response; service utilization; success; systemic inflammatory response; timeline; verification and validation

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.

项目概要 败血症是一种全身炎症反应，每年在美国导致超过 270,000 人死亡 血流感染（BSI）。事实证明，及时诊断和治疗 BSI 可以改善患者的病情 结果并减少住院时间。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，而且敏感性降低 在抗菌治疗的情况下。因此，迫切需要新的诊断方法 不需要培养物并提供更快、更准确的结果。 为了解决这一未满足的需求，HelixBind 开发了 RaPID（耐药性和病原体识别），这是一种完全 自动化的样本到答案平台，适合放置在整个医院。 RaPID 包括 台式分析仪操作一次性盒，能够识别和表征复杂的侵入性 直接从患者标本中进行感染，无需培养。由于无需培养，RaPID 测试不会受到以下因素的抑制 多种微生物感染或既往抗菌治疗。在此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测试菜单，具有单一 CFU/ml 灵敏度 大约3小时内。经过多项临床研究，该测试已证明灵敏度 >94% 且 >99% 测试菜单中与文化相关的特异性。由于该产品相对于现有替代品的优势 及其改善护理的潜力，FDA 于 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 BSI 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， 不仅证明了对抗性基因组的单 CFU/ml 敏感性，而且还能够 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。证明分析敏感性和特异性的研究将 完成了 RaPID/R 的盲法临床评估。这些研究将确保产品性能 符合规格和临床要求。同时，研究产品验证和设计 作为预提交流程的一部分，验证将完成并提交给 FDA。 为了在这个项目中取得成功，我们组建了一支在检测开发方面具有专业知识的优秀团队， 仪器仪表、消耗品制造、法规遵从性、临床微生物学和传染性 疾病。该团队在 FDA 批准的 IVD 平台和检测商业化方面拥有成功的记录。 我们将共同在前期工作的基础上完成产品开发。完成此操作后 项目完成后，我们将能够启动 FDA 批准所需的正式分析和临床研究。