SBIR Phase II: A Rapid, Sensitive Pathogen Typing and Antibiotic Sensitivity Test for Bloodstream Infections (COVID-19)

这个小型企业创新研究（SBIR）第二阶段项目的更广泛影响旨在开发一个更好的传染病管理时代，允许快速干预抗生素治疗，以阻止败血症30%的死亡率和相关的成本影响。全世界约有4900万病例，死亡率为25-30%，败血症每年夺去1100万人的生命。败血症病例每年增加8.7%。为了应对各种传染病，创新必须提供简单且负担得起的检测能力，类似于常规的入院血液分析。拟议的用于检测和治疗血流感染的抗真菌和抗菌药物敏感性测试可以通过改善患者管理和医院后勤来使患者受益。败血症是最昂贵的医疗保健挑战，估计每年的财务影响超过620亿美元。这种血流感染筛查检测可以影响整个护理过程-从最初的医院互动到患者护理和出院-通过早期识别感染，优化治疗和提高生存率。基于直接客户调查的估计和独立信息来源预测，美国每年有2.26亿次检测的商业机会（3600万次住院，4000万次重症监护患者，1.3亿次急诊就诊和2000万次术前评估）。拟议的项目可能会导致开发一种用户友好和负担得起的分析工具，用于早期检测血流感染，区分与脓毒症相关的细菌和真菌病原体，并在数小时内确定其抗生素敏感性。败血症是一个主要的公共卫生和经济问题，每2.8秒就有一人死亡。如果血流感染未被发现或未经治疗，患者可能会迅速升级为败血症或脓毒性休克，在没有适当抗生素治疗的情况下，死亡率每小时增加8%。在败血症发作之前快速准确地检测血流感染对于限制组织和器官损伤的程度、死亡率和相关的医院费用至关重要。拟议的创新包括使用FDA批准的称为Limulus Amebocyte Lysate的试剂进行临床血流感染和抗真菌抗菌药物敏感性测试，以指导治疗干预，以及对高风险患者人群进行常规监测。第二阶段的技术方法包括能力研究，这些研究将验证病原体的高通量检测，以及它们在临床血液标本中的抗菌药物敏感性和耐药性。此外，将进行测定的小型化和自动化，并被认为是未来体外诊断伙伴关系采用的关键。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The broader impact of this Small Business Innovation Research (SBIR) Phase II project seeks to develop an improved era of infectious disease management, allowing rapid intervention for antibiotic therapy to stem the 30% mortality rate and associated cost impact of sepsis. With some 49 million cases worldwide and a 25-30% mortality rate, sepsis claims 11 million lives annually. Sepsis cases have been increasing 8.7% per year. To address the full spectrum of infectious diseases, innovations must deliver simple and affordable testing capabilities similar to routine hospital admission blood analyses. The proposed antifungal and antibacterial susceptibility test for the detection and treatment of bloodstream infections could benefit patients by improving patient management and hospital logistics. Sepsis is the most expensive healthcare challenge, with an estimated financial impact of more than $62 billion per year. This bloodstream infection screening assay could impact the entire continuum of care – from initial hospital interactions through patient care and discharge – by identifying infections early, optimizing treatment, and increasing survival. Direct customer survey-based estimates and independent information sources project a U.S. commercial opportunity of 226 million annual assays (36 million hospital admissions, 40 million intensive care patients, 130 million emergency walk-ins, and 20 million presurgical evaluations). The proposed project could result in the development of a user-friendly and affordable analytical tool for early detection of bloodstream infections that differentiates bacterial and fungal pathogens associated with sepsis and determine their antibiotic sensitivity in hours. Sepsis is a major public health and economic concern that results in one human death every 2.8 seconds. If bloodstream infections go undetected or untreated, patients can quickly escalate into sepsis or septic shock with mortality chances increasing by 8% per hour without appropriate antibiotic administration. Rapid and accurate detection of a bloodstream infections prior to the onset of sepsis is critical to limit the extent of tissue and organ damage, mortality, and associated hospital costs. The proposed innovation includes the use of an FDA-approved reagent called Limulus Amebocyte Lysate for clinical bloodstream infections and antifungal antibacterial susceptibility testing to guide therapeutic interventions, and routine surveillance of high-risk patient populations. The technical approach for this Phase II encompasses proficiency studies that would validate high-throughput detection of pathogens, as well as their antimicrobial sensitivity and resistance profiles in clinical blood specimens. Additionally, assay miniaturization and automation would be performed and are considered critical for future in vitro diagnostic partnership adoption.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.