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.

项目摘要 现在，抗菌（AMR）感染的兴起和扩散使其对速度越来越重要 表型敏感性测试的可用性结果。对于AMR生物，广泛的 光谱抗菌疗法用于保护患者在生长所需的2天期间 越来越多的自动化敏感性测试（AST）方法的菌落和性能越来越多 太长等待确定有效的治疗剂，尤其是在快速移动的情况下 致命的血液感染或其他时间敏感的临床样本，例如古老的ICU UTI，儿科和 脑脊液样品。 特定诊断揭示™AST系统提供表型AST在≈5小时内导致表型，直接来自 阳性血液培养样品以及时间敏感的分离株稀释稀释液，允许相同的转移 修饰抗生素疗法。该系统基于专有，一次性，低成本的使用 小分子传感器（SMS）阵列对在微生物中发出的挥发物高度敏感 他们的成长。通过将此类传感器阵列片附加到多孔干抗生素板上， 系统检测到生长并以与基于浊度的肉汤相同的稳健精度调用MIC 微稀释金标准，但直接来自稀释的阳性血液培养样品，并在5小时内。 揭示系统继承的简单性使得具有相对低成本的仪器和处置， 实现合理的广泛采用，因此对患者结果和 医疗保健系统成本和性能。 特定的诊断已经达到或超过第2阶段NIAID SBIR赠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 商业仪器的Alpha版本的工程和制造。 2018年10月， 具体参加了在FDA举行的预选会议，并收到定义协议的指导 临床研究以证明两种阳性血液的揭示测定的准确性和可靠性 培养和分离稀释样品。 根据要求的IIB期，该提案的9个目标包括完成质量系统，ISO- 13485：2016年我们开发和制造过程的认证，临床的行为 在3个站点的研究以及分析研究和参考实验室确认参考方法 测定可以确认每个FDA要求的揭示性能，然后成功 510（k）提交和清理，允许在临床上使用显示系统 授予。