Rapid Low Cost Phenotypic Antibiotic Susceptibility Testing

项目摘要 抗菌素耐药(AMR)感染的上升和蔓延现在使得速度变得越来越重要 表型药敏试验结果的可用性。就AMR生物而言，广泛的- 光谱抗菌治疗用于在患者生长所需的2天期间保护患者 过夜自动药敏试验(AST)方法的菌落和性能日益增加， 等待太长时间才能确定有效的治疗剂，特别是在快速移动和 致命的血液感染或其他对时间敏感的临床样本，如老年ICU尿路感染、儿科和 脑脊液样本。 特定诊断显示™AST系统在≈5小时内提供表型AST结果，这两种结果都是直接从 阳性血液培养样本以及时间敏感的分离稀释液，允许相同的转移 抗生素治疗的改进。该系统是基于使用专有、一次性、低成本的 小分子传感器阵列对微生物释放的挥发物高度敏感 他们的成长。通过将这种传感器阵列的薄片连接到多个干燥的抗生素平板上， 系统检测生长并调用MIC，具有与基于浊度的肉汤相同的强大准确性 微量稀释金标准，但直接从稀释的阳性血培养样本，并在5小时内。 该显示系统固有简单性使得能够以相对较低的成本使用和一次性使用， 实现看似广泛的采用，从而对患者结局和 医疗保健系统的成本和性能。 特定诊断已达到或超过第二阶段NIAID SBIR拨款中定义的所有目标， 其中包括系统的特性，原型RO版本的开发，以及 商业仪器的阿尔法版本的设计和制造。2018年10月， 特约人员在FDA参加了一次小组会议，收到了关于以下要求的指导 临床研究证实两种阳性血的REVIEW分析的准确性和可靠性 培养并分离稀释样品。 根据要求的第二阶段B，该提案的9个目标包括完成质量体系、ISO- 13485：2016年对我们的开发和制造流程、临床行为的认证 3个地点的研究，以及分析研究和参考实验室验证性参考方法 根据FDA的要求进行检测，以确认披露性能，然后成功 510(K)提交和批准，允许在#年的最后一年内临床使用揭示系统 格兰特。

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.