Rapid Low Cost Phenotypic Antibiotic Susceptibility Testing

项目摘要 抗生素耐药性（AMR）感染的上升和蔓延现在使得加快速度变得越来越重要 表型药敏试验结果的可用性。在AMR微生物的情况下，广泛的- 用于在生长所需的2天期间保护患者的广谱抗菌治疗 菌落和过夜自动化敏感性测试（AST）方法的性能，越来越多地， 太长的等待，以确定有效的治疗剂，特别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，如老年ICU UTI，儿科， 脑脊液样本 Specific Diagnostics Reveal™ AST系统可在15小时内提供表型AST结果， 阳性血培养样本以及来自时间敏感分离株稀释液的样本，允许相同偏移 修改抗生素治疗。该系统是基于专有使用，一次性使用，成本低 小分子传感器（SMS）阵列对微生物释放的挥发物高度敏感， 他们的成长。通过将这样的传感器阵列的片附着到多孔干燥的抗生素板， 系统检测生长并以与基于浊度的肉汤相同的稳健准确度调用MIC 微量稀释金标准，但直接来自稀释的阳性血培养样品，并在5小时内。 Reveal系统固有的简单性使其成为一种相对低成本的仪器和一次性用品， 能够合理地广泛采用，并因此对患者结局和 医疗保健系统成本和性能。 特定诊断已达到或超过第2阶段NIAID SBIR补助金中定义的所有目标， 其中包括系统的特性，原型RUO版本的开发， 商业仪器的alpha版本的工程和制造。2018年10月， Specific参加了FDA的预提交会议，接受了定义以下内容所需方案的指南： 证明Reveal检测试剂盒在两种阳性血液中的准确性和可靠性的临床研究 培养并分离稀释样品。 根据要求的第二B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过程，临床试验的进行 在3个研究中心进行的研究，沿着分析研究和参考实验室确证性参考方法 根据FDA要求进行检测，以确认Reveal性能，然后成功 510（k）提交和批准，允许Reveal系统在最后一年的临床使用 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.