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

摘要/摘要 尿路感染(UTI)是美国最常见的感染类型之一，据估计 1050万次与UTI相关的办公室访问，200-300万次急诊科访问，以及100,000多次 在美国，每年的住院费用至少为35亿美元。60%的女性将在 一生中至少有一次急性尿路感染。25%-50%的女性有多次反复感染需要反复 抗生素。尿路感染和不断增加的高水平抗生素耐药性是对人类健康的严重威胁。证据 过去十年的增长有力地表明，这些感染的高发病率和反复发作的性质 而广谱抗菌药的频繁使用正在推动新的 多药耐药(MDR)UTI菌株。现在每三个尿路感染中就有一个对磺胺甲恶唑/甲氧苄啶耐药 (曾经是标准治疗)。五分之一的人对五种或五种以上的抗生素有抗药性，有些现在是抗药性的。 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城疫的出现至关重要 新的MDR尿路感染，并最大限度地发挥目前可用的治疗方案的疗效。当前UTI诊断 方法需要耗时的分析前生物体分离和浓缩，而不是 提供应对这一挑战所需的全面AST和MIC数据。事实上，最大的劳动力 临床诊断实验室的组成部分用于处理和诊断尿路感染。新的 需要各种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。理想情况下，这样的系统将允许可操作的、当天的、直接从样本中检测多个 无需细菌分离或培养的药物。 Cobio的PhAAST-MIC在SBIR第一阶段成功开发，用于尿液中的大肠杆菌，使同步 在5小时内直接从尿样中检测表型ID、AST和MIC。目前没有可用的 诊断平台允许所有三种数据类型的同步当天结果的这种组合。 正如设想的那样，第二阶段将扩展PhAAST-MIC功能，以包括其他最流行的MDR 尿路病原体-特别是粪肠球菌、肺炎克雷伯菌、腐生葡萄球菌、 铜绿假单胞菌和奇异变形杆菌，并为FDA 510(K)清除开发一条调控途径。 测试产生的数据将提供量身定制的抗菌治疗，旨在减少测试时间和 改善抗生素管理和患者预后。科比奥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.