Rapid phage-amplified immunoassay for phenotypic UTI diagnosis and antimicrobial susceptibility testing

摘要/概要 泌尿道感染（UTI）是美国最常见的感染类型之一， 10.5 100万次UTI相关门诊就诊，200 - 300万次急诊就诊，以及超过10万次 美国每年的住院费用至少为35亿美元。60%的女性会经历 至少有一次急性尿路感染25-50%的妇女有多次复发性感染，需要反复治疗。 抗生素UTI和不断增加的高水平抗生素耐药性严重威胁着人类健康。证据 在过去十年中获得的研究结果有力地表明，这些感染的高发病率和复发性 广谱抗菌药物的频繁使用正在促进新的 多药耐药（MDR）UTI菌株。三分之一的UTI现在对磺胺甲恶唑/甲氧苄啶耐药 (once标准治疗）。五分之一的人对五种或五种以上的抗生素有抗药性，有些人现在已经有抗药性了。 所有可用的药物。 快速识别和评估抗生素耐药性的能力对于最大限度地减少 新的MDR UTI，并最大限度地提高目前可用治疗方案的疗效。当前UTI诊断 这些方法需要耗时的分析前微生物分离和富集， 提供应对这一挑战所需的全面AST和MIC数据。事实上， 临床诊断实验室的组成部分花费在处理和诊断UTI上。新 我们需要一些方法来提高我们进行快速ID、AST和MIC的能力，以满足诊断要求。 要求。理想地，这样的系统将允许可操作的、同一天的、直接从样本测试多种微生物。 药物，而不需要细菌分离或培养。 Cobio的PhAAST-MIC在SBIR第一阶段成功开发，用于E。大肠杆菌，使同时 表型ID、AST和MIC检测直接从尿液标本在5小时内。目前没有可用的 诊断平台允许所有三种数据类型的同时同日结果的这种组合。 按照设想，第二阶段将扩大PhAAST-MIC能力，以包括其他最普遍的MDR 泌尿病原体-特别是粪肠球菌，肺炎克雷伯氏菌，金黄色葡萄球菌， 铜绿假单胞菌和奇异变形杆菌，并制定FDA 510（k）许可的监管途径。 测试产生的数据将提供定制的抗菌治疗，旨在减少测试时间， 改善抗生素管理和患者结果。Cobio的专业研发人员将继续与 科罗拉多大学和科罗拉多儿童医院的医生和抗生素耐药性专家。

Abstract/ Summary Urinary tract infections (UTIs) are among the most common infection type in the U.S resulting in an estimated 10.5 million UTI-related office visits, 2-3 million emergency department visits, and over 100,000 hospitalizations in the U.S. annually at a cost of at least $3.5 billion. Sixty percent of women will experience at least one acute UTI in their lifetime. 25-50% of women have multiple recurrent infections requiring repeated antibiotics. UTIs and increasing high-level antibiotic resistance are a serious threat to human health. Evidence gained over the past decade strongly suggests that the high incidence and recurrent nature of these infections and the frequent use of broad-spectrum antimicrobials to treat them is promoting the emergence of new multidrug resistant (MDR) UTI strains. One in three UTIs are now sulfamethoxazole/trimethoprim resistant (once the standard treatment). One in five are resistant to five or more antibiotics and some are now resistant to all available drugs. The ability to ID and assess antibiotic resistance rapidly is critically important to minimize the emergence of new MDR UTIs and to maximize the efficacy of currently available treatment options. Current UTI diagnostic approaches require time-consuming pre-analysis organism isolation and enrichment and do not provide the comprehensive AST and MIC data needed to meet this challenge. Indeed, the largest labor component of the clinical diagnostic laboratory is spent processing and diagnosing UTIs. New approaches are needed to improve our ability to perform rapid ID, AST and MIC in order meet diagnostic demands. Ideally, such a system would allow actionable, same-day, direct-from-specimen testing of multiple drugs without the need for bacterial isolation or cultivation. Cobio’s PhAAST-MIC, successfully developed in SBIR Phase I for E. coli in urine, enables simultaneous phenotypic ID, AST, and MIC testing directly from urine specimens within 5 hours. No currently available diagnostic platform allows for this combination of simultaneous same-day results for all three data types. As envisioned, Phase II will expand PhAAST-MIC capabilities to include the other most prevalent MDR uropathogens—specifically Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus saprophyticus, Pseudomonas aeruginosa and Proteus mirabilis and develop a regulatory pathway for FDA 510(k) clearance. Data generated by the test will provide tailored antimicrobial therapy designed to reduce testing times and improve antibiotic stewardship and patient outcomes. Cobio’s expert R&D staff will continue to team with physicians and antibiotic resistance experts at the University of Colorado and Children’s Hospital Colorado.