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

抗生素耐药性是一个全球性的医疗危机，迫使医生治疗常见的 感染性疾病的抗生素。新的诊断策略迫切需要 需要快速病原体鉴定/定量（IDQ）和抗菌药物敏感性 检测（AST），以指导尿路感染（UTI）患者的抗生素选择。 MicrobeDx将设计和测试UroLogic，这是一种高度自动化的仪器和检测盒。 该系统执行快速、准确的病原体IDQ和AST，周转时间从 样品至读数的时间分别为30和150分钟。 虽然经过验证，但我们目前的分析是手动的，需要单独的阅读器。手动 测定已经提供了高灵敏度和特异性。我们正在开发一种全自动， 近护理检测系统，是负担得起的诊所和传统的初级保健办公室。 在第一阶段，我们的具体目标是验证IDQ和AST检测的概念， 集成到满足诊断里程碑的alpha原型UroLogic系统中 需要尿液样本来指导UTI治疗。 目的1：评价集成IDQ测定。我们将评估流体和分析 α原型UroLogic IDQ检测试剂盒用于鉴别和定量 细菌和真菌微生物作为分离株和尿液标本。将比较结果 用标准的微生物生化和平板培养方法。 目的2：评价AST综合测定。我们将评估流体和分析 用于抗菌药物敏感性试验的α原型UroLogic AST检测试剂盒的性能 革兰氏阴性菌作为分离株和尿液标本。表型方法，如 我们是革兰氏阴性菌易感性的最佳预测者 可行性测试：alpha原型系统必须证明具有临床意义 LOD（104 cfu/ml）和分析IDQ和AST准确度符合FDA标准。此外， 商品设备必须达到价格点（4美元IDQ墨盒，5美元AST墨盒，10，000美元 #24453;，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， 临床上可用的beta原型，从第一阶段的反馈中得知，并测试整个 临床环境中的系统。在后期IIb期资金的支持下，我们将评估 随机对照试验（RCT）中的器械，以确定分析准确性、临床实用性 医疗保健的经济影响。

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.