SBIR Phase I: Development of point-of-care diagnostics to direct the appropriate use of antibiotics for the treatment of high-risk urinary tract infections

这个小企业创新研究第一阶段项目将提供一种快速诊断测试的关键开发，该测试能够提供从疑似尿路感染(UTIs)患者身上收集的样本的抗生素耐药性概况。在美国，大约有800万例尿路感染，而且越来越多的尿路感染是由耐药细菌引起的，这些细菌使这些感染的治疗大大复杂化。一般来说，患有抗药性尿路感染的患者需要更长的时间才能接受适当的治疗，从而导致疾病进展和继发合并症的风险更大。能够快速识别抗药性尿路感染的诊断测试将对这些感染的治疗产生强大和积极的影响。这项拟议的工作旨在优化和扩展第一代诊断试验的诊断能力，以创建一种全面的检测方法，可以在几分钟内检测到耐药的UTI。拟议的SBIR第一阶段项目将推动双酶触发级联技术(DETECT)的开发，该技术旨在检测尿路病原体产生的低丰度β-内酰胺酶，以水解β-内酰胺酶抗生素，使其无效。产生β-内酰胺酶的尿路病原体的存在可能会极大地复杂化临床决策，因为这些病原体通常对用于治疗尿路感染(UTIs)的一线抗生素具有耐药性。作为一种诊断系统，检测具有显著改善尿路感染护理的潜力，因为它能够直接从尿样中快速识别产生β-内酰胺酶的尿路病原体。这项技术的临床可行性之前已经在临床尿样中得到了证明，首先针对的是一种名为CTX-MS的β-内酰胺酶亚群。这项拟议的工作旨在调整和优化第一代系统，以提供一种全面的诊断测试，可以准确地识别所有临床上重要的β-内酰胺酶。这项技术提供了一种简单、低技术和成本效益高的方式，无需处理、尿液沉淀或离心或复杂的仪器即可告知患者治疗情况。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This Small Business Innovation Research Phase I project will provide critical development of a rapid diagnostic test capable of delivering the antibiotic resistance profile of a sample collected from patients suspected of suffering from urinary tract infections (UTIs). In the US there are approximately 8 million UTIs, and an increasing number of are caused by drug-resistant bacteria that significantly complicate the treatment of these infections. In general, patients suffering from a drug resistant UTI take longer to receive appropriate treatment, resulting in a greater risk of disease progression and onset of secondary comorbidities. Diagnostic tests that can rapidly identify drug-resistant UTIs will have a strong and positive impact on the treatment of these infections. The proposed work aims to optimize and expand the diagnostic capacity of a first-generation diagnostic assay to create a fully comprehensive test that can detect a drug-resistant UTI in minutes.The proposed SBIR Phase I project will advance the development of a dual-enzyme trigger-enabled cascade technology (DETECT), developed to detect low-abundant beta-lactamases produced by uropathogens to hydrolyze beta-lactamase antibiotics, rendering them ineffective. The presence of beta-lactamase-producing uropathogens can greatly complicate clinical decision-making because these pathogens are regularly resistant to the first-line antibiotics considered for treatment of urinary tract infections (UTIs). DETECT, applied as a diagnostic system, holds the potential to significantly improve the care of UTIs because it enables rapid identification of beta-lactamase-producing uropathogens directly from urine samples. The clinical feasibility of the technology has been demonstrated previously using clinical urine samples, first targeting a subset of beta-lactamases known as CTX-Ms. The proposed work aims to tune and optimize the first-generation system to offer a comprehensive diagnostic test that can accurately identify all of the clinically important beta-lactamases. This technology provides a simple, low-tech, and cost-effective way to inform patient treatment without the need of processing, urine sedimentation or centrifugation, or sophisticated instrumentation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.