SBIR Phase II: Development of a urine dipstick test that can guide immediate and appropriate antibiotic therapy for treatment of complicated urinary tract infections

该小型企业创新研究（SBIR）II期项目的更广泛影响/商业潜力是改善复杂性尿路感染（cUTI）患者的临床结局和生活质量。今天，cUTI在美国每年有40万例住院治疗。不幸的是，多重耐药病原体是cUTI的常见原因。许多人对一线抗生素（头孢曲松）具有耐药性，该抗生素被用作这种情况的经验性治疗。然而，导致cUTI的多药耐药病原体的高发生率延迟了患者接受更适当治疗的时间。cUTI患者接受适当治疗的时间延迟归因于住院时间延长以及发病率和死亡率风险增加。目前用于诊断耐药cUTI的标准测试从获得患者样本开始需要2-3天。因此，迫切需要能够快速告知UTIs初始治疗的诊断测试，以改善患者护理。该小型企业创新研究（SBIR）II期项目旨在开发一种快速泌尿诊断测试，以检测头孢曲松耐药的尿路病原体。早期检测一线治疗的耐药性将使抗生素处方能够得到通知，从而降低患者疾病进展的风险。在UTI的情况下，疾病进展可导致严重的侵袭性感染，主要是败血症。因此，能够检测一线抗生素耐药性的诊断能够实现早期治疗干预，减少适当治疗的时间并降低疾病进展的风险。减少治疗时间也降低了与耐药cUTI相关的医疗保健成本，因为与易感感染相比，疾病进展与住院时间增加相关。第二阶段项目的完成将开发出一种原型测试，可以在不到5分钟的时间内提供有关头孢曲松敏感性的可操作信息。该项目的成功将为临床医生提供cUTI的诊断解决方案，可以立即采取行动，以改善患者的治疗效果，并通过防止不必要地使用不适当的抗生素来帮助抗生素管理。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to improve the clinical outcomes and quality of life for patients suffering from complicated urinary tract infections (cUTI). Today, cUTIs account for 400,000 hospitalizations annually in the United States. Unfortunately, multidrug resistant pathogens are a common cause of cUTI. Many are resistant to the first-line antibiotic (Ceftriaxone), which is used as the empiric treatment of this condition. However, the high incidence of multidrug resistant pathogens causing cUTI delays the time until patients receive more appropriate treatment. Delayed time to appropriate therapy in cUTI has been attributed to extended hospital stays and an increased risk of morbidity and mortality. The current standard test for diagnosing a drug-resistant cUTI takes 2-3 days from obtaining a patient sample. Therefore, diagnostic tests that can rapidly inform the initial treatment of UTIs are urgently needed to improve patient care.This Small Business Innovation Research (SBIR) Phase II project aims to develop a rapid urinary diagnostic test that will enable the detection of ceftriaxone-resistant uropathogens. Early detection of resistance to first-line therapies would enable antibiotic prescribing to be informed, reducing the risk of disease progression in patients. In the case of UTIs, disease progression can lead to severely invasive infections, predominately sepsis. Therefore, diagnostics that can detect resistance to first-line antibiotics enable early treatment interventions, reducing the time to appropriate treatment and reducing the risk of disease progression. Decreased treatment time also lowers the healthcare costs associated with drug-resistant cUTI, as disease progression is associated with increased lengths of hospital stays compared to susceptible infections. The completion of the Phase II project will yield the development of a prototype test that can provide actionable information regarding ceftriaxone susceptibility in less than 5 minutes. This project’s success will provide clinicians with a diagnostic solution for cUTIs that can be acted on immediately to improve patient outcomes and aid antibiotic stewardship by preventing the unnecessary use of inappropriate antibiotics.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.