Rapid Low Cost Phenotypic Antibiotic Susceptibility Testing

快速低成本表型抗生素敏感性测试

• 批准号: 10009754
• 负责人: PAUL RHODES
• 金额: $ 99.87万
• 依托单位: SPECIFIC DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-07 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10009754
• 关键词: Acute; Adopted; Adoption; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Antimicrobial susceptibility; Biological Assay; Blood; Case Study; Cause of Death; Cerebrospinal Fluid; Certification; Cessation of life; Childhood; Clinical; Clinical Research; Communities; Computer software; Data Collection; Data Reporting; Detection; Development; Diagnostic; Elderly; Engineering; Evolution; Goals; Gold; Grant; Growth; Healthcare; Healthcare Systems; Hospital Costs; Hospitals; Hour; Individual; Laboratories; Marketing; Medical; Methods; Microbiology; Minimum Inhibitory Concentration measurement; Modification; Molecular; National Institute of Allergy and Infectious Disease; Organism; Patient Care; Patient-Focused Outcomes; Patients; Performance; Phase; Phenotype; Predisposition; Preparation; Process; Protocols documentation; Readiness; Reporting; Research; Resistance; Sampling; Sepsis; Site; Small Business Innovation Research Grant; Societies; Specimen; Speed; System; Systems Development; Test Result; Testing; Therapeutic Agents; Time; Treatment Efficacy; United States; Urinary tract infection; antimicrobial; antimicrobial resistant infection; base; clinical research site; comparative; cost; design; effective therapy; hospital laboratories; instrument; manufacturing process; meetings; microorganism; mortality; preclinical study; prototype; sensor; sensor technology; small molecule; tool

Project Summary The rise and spread of antimicrobial-resistant (AMR) infection now makes it increasingly vital to speed the availability of phenotypic susceptibility test results. In the case of AMR organisms, the broad- spectrum antimicrobial therapy used to protect patients during the 2 day period required for growth of colonies and performance of overnight automated susceptibility testing (AST) methods is, increasingly, too long to wait to identify an effective therapeutic agent, especially in the case of fast moving and deadly blood infection, or other time-sensitive clinical samples, such as elderly ICU UTI’s, pediatric, and cerebrospinal fluid samples. Specific Diagnostics Reveal™ AST system delivers phenotypic AST results in ≈5 hours, both directly from positive blood culture samples as well as from time-sensitive isolate dilutions, allowing same-shift modification of antibiotic therapy. The system is based on the use of proprietary, disposable, low cost small molecular sensor (SMS) array highly sensitive to the volatiles emitted by microorganisms during their growth. By attaching a sheet of such sensor arrays to a multi-well dried antibiotic plates, the system detects growth and calls MIC with the same robust accuracy as the turbidity-based broth microdilution gold standard, but directly from a diluted positive blood culture sample, and in 5 hours. The Reveal system’s inherent simplicity enables a comparatively low-cost instrument and disposable, enabling plausibly broad adoption and consequently significant impact on both patient outcome and health care system cost and performance. Specific Diagnostics has met or exceeded all the objectives defined in the Phase 2 NIAID SBIR grant, which included characterization of the system, development of a prototype RUO version, and the engineering and manufacture of the alpha version of the commercial instrument. In October of 2018, Specific attended a pre-sub meeting at FDA, receiving guidance defining the protocols required for clinical studies to demonstrate the accuracy and reliability of the Reveal assay with both positive blood culture and isolate dilution samples. Under the requested Phase IIB, the proposal’s 9 objectives include completion of a quality system, ISO- 13485:2016 certification for our development and manufacturing processes, the conduct of clinical studies at 3 sites, along with the analytical studies and reference lab confirmatory reference method assays to enable confirmation of Reveal performance per FDA requirements, followed by successful 510(k) submittal and clearance, allowing the clinical use of the Reveal system during the last year of the grant.

项目概要 抗菌素耐药性 (AMR) 感染的兴起和蔓延使得加快速度变得越来越重要 就 AMR 生物体而言，表型敏感性测试结果的可用性。 用于在细菌生长所需的 2 天内保护患者的谱抗菌疗法 隔夜自动药敏试验 (AST) 方法的菌落和性能日益受到关注 等待确定有效治疗剂的时间太长，尤其是在快速移动和快速发展的情况下 致命的血液感染或其他时间敏感的临床样本，例如老年 ICU 尿路感染、儿科样本和 脑脊液样本。 Specific Diagnostics Reveal™ AST 系统可在约 5 小时内提供表型 AST 结果，均直接来自 阳性血培养样本以及时间敏感的分离稀释液，允许同班 该系统基于使用专有的、一次性的、低成本的抗生素疗法。 小分子传感器 (SMS) 阵列对微生物在生产过程中释放的挥发物高度敏感 通过将一片这样的传感器阵列附着到多孔干燥的抗生素板上， 系统检测生长并调用 MIC，其准确度与基于浊度的肉汤相同 微量稀释金标准，但直接来自稀释的阳性血培养样本，并在 5 小时内进行。 Reveal 系统固有的简单性使得仪器成本相对较低并且是一次性的， 实现合理的广泛采用，从而对患者的治疗结果和治疗效果产生重大影响 医疗保健系统的成本和绩效。 Specific Diagnostics 已达到或超过 NIAID SBIR 第 2 阶段拨款中定义的所有目标， 其中包括系统的表征、原型 RUO 版本的开发以及 2018 年 10 月，商业仪器 alpha 版本的设计和制造。 Specific 参加了 FDA 的预分会议，接受了定义所需方案的指导 临床研究证明 Reveal 检测对阳性血液的准确性和可靠性 培养并分离稀释样品。 根据所要求的第 IIB 阶段，该提案的 9 个目标包括完成质量体系、ISO- 13485:2016 认证我们的开发和制造流程、临床试验的开展 在 3 个地点进行的研究，以及分析研究和参考实验室验证参考方法 根据 FDA 要求进行测定，以确认 Reveal 性能，然后成功 510(k) 提交和批准，允许 Reveal 系统在最后一年进行临床使用 授予。