I-Corps: Antibiotic susceptibility test kits

I-Corps项目更广泛的影响/商业潜力是开发一种能够快速检测细菌和抗生素敏感性测试的工具。对检测细菌性败血症和确定适当抗生素的更快、灵敏和负担得起的诊断工具的需求尚未得到满足。在治疗败血症时，在数小时内定制抗生素治疗的能力尤为重要。每年，败血症会影响100万至300万美国患者，导致27万人死亡，造成的损失超过600亿美元。通过快速诊断和早期有效治疗，大多数败血症相关死亡是可以预防的。目前的护理标准涉及平均3天的周转时间。缩短诊断和开始有效治疗的时间有可能显著改善患者的预后，降低医院费用，并促进抗菌素管理。竞争技术需要病原体识别和培养细菌到可检测的密度，两者都增加了总体诊断时间。此外，竞争对手是基于仪器的，这使得许多医院在经济上无法获得它们。提出的技术不需要预测试步骤，并依赖于标准的临床实验室设备。此外，低收入地区败血症死亡率较高，所提出的技术可能改善所有败血症患者的预后，包括最脆弱的患者。这个I-Corps项目是基于开发一种用于细菌生长检测和抗生素敏感性分析的新工具。提出的技术对探针模拟细菌细胞表面构建块与放大比色测定创建一个溶液，以检测细菌败血症和识别适当的抗生素。概念验证数据表明，所提出的检测方法可以在不到4.5小时内快速检测细菌生长并区分生长细菌和非生长细菌，包括抗生素敏感性分析。此外，数据还表明，检测是剂量、细菌密度和时间相关的，并且与常见的脓毒症引起的细菌兼容，而不管它们的细胞表面结构如何。此外，该分析可以使用标准临床实验室中的设备进行。虽然目前的重点是开发一种试剂盒，用于血液传播致病菌的快速检测和药物敏感性分析，但该技术可能适用于检测食品和生物医学生产设施等各种环境中的细菌生长。该奖项反映了美国国家科学基金会的法定使命，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 I-Corps project is the development of a tool that enables rapid bacterial detection and antibiotic susceptibility testing. There is a critical unmet need for faster, sensitive, and affordable diagnostic tools to detect bacterial sepsis and identify appropriate antibiotics. The ability to customize antibiotic treatment within hours is particularly critical when treating sepsis. Each year, sepsis impacts 1-3 million U.S. patients, leads to 270,000 deaths, and costs over $60 billion. Most sepsis associated deaths are preventable with rapid diagnosis and early, effective treatment. Current standard of care involves an average 3-day turnaround. Shortening the time to diagnosis and initiation of effective treatment has the potential to dramatically improve patient outcomes, reduce hospital costs, and promote antimicrobial stewardship. Competing technologies require pathogen identification and growing bacteria to a detectable density, both adding to the overall diagnostic timeline. Furthermore, competitors are instrument-based, making them financially inaccessible to many hospitals. The proposed technology does not require pre-test steps and relies on standard clinical lab equipment. In addition, sepsis mortality is higher in low-income areas, and the proposed technology may improve outcomes for all sepsis patients, including the most vulnerable.This I-Corps project is based on the development of a novel tool for bacterial growth detection and antibiotic susceptibility profiling. The proposed technology pairs probes that mimic bacterial cell surface building blocks with an amplifiable colorimetric assay to create a solution to detect bacterial sepsis and identify appropriate antibiotics. The proof-of-concept data suggest that the proposed assay may rapidly detect bacterial growth and distinguish growing from nongrowing bacteria, including antibiotic susceptibility profiling, in less than 4.5 hours. In addition, the data also show that detection is dose-, bacterial density-, and time-dependent, and compatible with common sepsis-causing bacteria regardless of their cell surface architecture. Further, the assay may be performed using equipment found in standard clinical labs. While the current focus is on developing a kit for rapid detection and drug susceptibility profiling of blood-borne pathogenic bacteria, the technology may be adapted to detect the growth of bacteria in a variety of settings such as food and biomedical manufacturing facilities.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.