I-Corps: Antibiotic susceptibility test kits

这个I-Corps项目的更广泛的影响/商业潜力是开发一种工具，能够快速进行细菌检测和抗生素敏感性测试。对于检测细菌性败血症和鉴定适当的抗生素的更快、灵敏和负担得起的诊断工具存在关键的未满足的需求。在治疗脓毒症时，在数小时内定制抗生素治疗的能力尤其重要。每年，败血症影响1-3百万美国患者，导致270，000人死亡，花费超过600亿美元。大多数脓毒症相关死亡是可以通过快速诊断和早期有效治疗来预防的。目前的护理标准涉及平均3天的周转。缩短诊断和启动有效治疗的时间有可能大大改善患者的预后，降低医院成本，并促进抗菌药物的管理。相互竞争的技术需要病原体识别和细菌生长到可检测的密度，这两者都增加了整体诊断时间轴。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。所提出的技术不需要预测试步骤，并且依赖于标准临床实验室设备。此外，脓毒症死亡率在低收入地区较高，拟议的技术可能会改善所有脓毒症患者的结果，包括最脆弱的I-Corps项目是基于细菌生长检测和抗生素敏感性分析的新工具的开发。所提出的技术将模拟细菌细胞表面构建块的探针与可重复的比色测定配对，以创建检测细菌败血症和鉴定适当抗生素的解决方案。概念验证数据表明，拟议的检测方法可以在不到4.5小时的时间内快速检测细菌生长并区分生长的细菌和非生长的细菌，包括抗生素敏感性分析。此外，数据还表明，检测是剂量，细菌密度和时间依赖性的，并与常见的败血症引起的细菌，无论其细胞表面结构兼容。此外，可以使用标准临床实验室中发现的设备进行测定。虽然目前的重点是开发一个试剂盒快速检测和药物敏感性分析的血液传播的病原菌，该技术可能适用于检测细菌的生长在各种设置，如食品和生物医学制造设施。这一奖项反映了NSF的法定使命，并已被认为是值得的支持，通过评估使用基金会的知识价值和更广泛的影响审查标准。

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.