UroLogic: Rapid, Near-to-Care Identification and Antimicrobial Susceptibility Testing of Microbes in Urine Specimens from Outpatients with Suspected Urinary Tract Infection

抗生素耐药性是一场全球医疗危机，迫使医生治疗常见的 用更有效的抗生素感染传染病。迫切需要新的诊断策略 病原体快速鉴定/定量(IDQ)和抗菌药敏感性所需 试验(AST)指导尿路感染(UTI)患者选择抗生素。 MicrobeDx将设计和测试尿路系统，这是一种高度自动化的仪器和药盒 快速、准确地执行病原体IDQ和AST的系统，周转时间从 样品至读数分别为30分钟和150分钟。 虽然经过验证，但我们目前的检测都是手动的，需要单独的阅读器。手册 检测具有很高的敏感性和特异性。我们正在开发一种全自动、 诊所和传统初级保健办公室负担得起的临终关怀化验系统。 在第一阶段，我们的具体目标是验证IDQ和AST分析可以 集成到符合诊断里程碑的阿尔法原型泌尿系统中 尿液标本需要用于指导尿路感染的治疗。 目的1：对IDQ综合测定法进行评价。我们将对流体和分析进行评估 α-原型泌尿系IDQ检测技术在尿路感染诊断和定量中的应用 细菌和真菌作为分离物和尿样。结果将会被比较 采用标准的微生物、生化和电镀方法。 目的2：对AST综合测定法进行评价。我们将对流体和分析进行评估 α-原型泌尿系AST法在药敏试验中的应用 革兰氏阴性杆菌作为分离株和尿样。表型方法，如 我们的是最好的革兰氏阴性敏感度预测因子。 可行性测试：阿尔法原型系统必须证明具有临床意义 LOD(104CFU/ml)和分析IDQ及AST准确度均符合FDA标准。此外，该项目的成本 商品设备必须达到一个价格点(4美元IDQ墨盒、5美元AST墨盒、10,000美元 工具)低到足以广泛传播。 在未来的SBIR第二阶段研究中，将进行额外的工程修改，使其成为 临床可用的测试原型，如来自阶段I的反馈所告知的，并测试整个 系统在临床环境中的应用。在稍后的第IIb期基金的支持下，我们会评估 该装置在随机对照试验(RCT)中用于确定分析准确性、临床实用性、 和医疗保健经济影响。

Antibiotic resistance is a global healthcare crisis that is forcing physicians to treat common infectious diseases with ever more potent antibiotics. New diagnostic strategies are urgently needed for rapid pathogen identification/quantification (IDQ) and antimicrobial susceptibility testing (AST) to guide antibiotic selection for patients with urinary tract infection (UTI). MicrobeDx will design and test UroLogic, a highly automated, instrument and cartridge system that performs rapid, accurate pathogen IDQ and AST with turnaround times from sample to readout of 30 and 150 minutes, respectively. While validated, our current assays are manual and require a separate reader. The manual assays have delivered high sensitivity and specificity. We are developing a fully automated, near-to-care assay system that is affordable for clinics and conventional primary care offices. In Phase I, our Specific Aims are proof-of-concept validation that the IDQ and AST assays can be integrated into an alpha-prototype UroLogic system that meets the diagnostic milestones required for urine specimens to guide therapy for UTI. Aim 1: Evaluation of the Integrated IDQ Assay. We will evaluate the fluidic and analytic performance of the alpha-prototype UroLogic IDQ assay for identification and quantification of bacterial and fungal organisms as isolates and in urine specimens. Results will be compared with standard microbiological biochemical and plating methods. Aim 2: Evaluation of the Integrated AST Assay. We will evaluate the fluidic and analytic performance of the alpha-prototype UroLogic AST assay for antimicrobial susceptibility testing of Gram-negative bacteria as isolates and in urine specimens. Phenotypic methods such as ours are the best predictors of Gram-negative susceptibility. Tests of Feasibility: The alpha prototype system must demonstrate a clinically meaningful LOD (104 cfu/ml) and analytic IDQ and AST accuracy to FDA standards. In addition, the cost of goods device must achieve a price point ($4 IDQ cartridge, $5 AST cartridge, $10,000 instrument) low enough to allow broad dissemination. In future SBIR Phase II studies, additional engineering modifications will be to make this a clinically usable beta-prototype, as informed by feedback from Phase I, and test the entire system in clinical settings. Supported by later Phase IIb funds, we will then evaluate the use of the device in a randomized controlled trial (RCT) to determine analytic accuracy, clinical utility, and healthcare economic impacts.