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

SBIR 第一阶段：针对血流感染 (COVID-19) 的快速、敏感病原体分型和抗生素敏感性测试

• 批准号: 2101278
• 负责人: Rachel Tinker-Kulberg
• 金额: $ 25.58万
• 依托单位: Kepley Biosystems Incorporated
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2101278&HistoricalAwards=false
• 关键词: SBIR; Phase; Rapid; Sensitive; Pathogen

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project would establish a rapid, sensitive pathogen typing and antibiotic sensitivity test for Bloodstream Infections (BSI) that could help guide early antibiotic therapy. Timely and accurate diagnosis of BSI would decrease the incidence of sepsis, as well as unnecessary or inappropriate antibiotic administration that can contribute to pathogen mutation and antimicrobial resistance (AMR). The risk of unnecessary or under-prescribed antibiotics during the COVID-19 pandemic has intensified future AMR threats, especially given that the incidence of bacterial sepsis occurs in 1 out of 7 COVID-19 inpatients, with a 50% mortality rate. Thus, a rapid, reliable in vitro diagnostic test for BSI would improve patient outcomes and have a measurable impact on quality of care, infection control, and overall healthcare management.The proposed technology for blood stream infection (BSI) detection and antibiotic susceptibility testing (AST) is rapid, highly sensitivity, and requires a low specimen volume. The assay would provide advantages over current standards of care (blood culture; BC), which typically require 24 to 72-hours to confirm the presence of a BSI. Additionally, this novel BSI assay does not require complex amplification steps (polymerase chain reaction; PCR) to detect pathogens. Given sepsis mortality rates increase by 7.6% per hour without appropriate antibiotic administration, septic patient care and survival demands early screening innovations that quickly and easily type species and determine AST to guide responsible antibiotic administration. The delayed results associated with current BSI testing methods hinders effective antibiotic selection, accuracy and timing. The proposed technology is comprised of a patent-pending bloodborne pathogen enrichment innovation that combines functionalized magnetic beads and the unique Limulus Amebocyte Lysate (LAL) substrate. The assay is built on three principles: (1) LAL contains highly sensitive proteins capable of detecting cell wall markers on gram-negative bacteria and fungi; (2) Differential LAL blocking would distinguish fungal and bacterial infection; and (3) Inclusion of a silkworm larvae plasma would provide a colorimetric output that detects gram-positive bacteria.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.

这一小企业创新研究(SBIR)第一阶段项目的更广泛影响/商业潜力将建立一种快速、敏感的血液感染(BSI)病原体分型和抗生素敏感性测试，有助于指导早期抗生素治疗。及时、准确地诊断BSI将减少脓毒症的发生率，以及可能导致病原体突变和抗菌素耐药性(AMR)的不必要或不适当的抗生素应用。在新冠肺炎大流行期间，不必要或处方不足的抗生素的风险加剧了未来的抗药性威胁，特别是考虑到新冠肺炎每7名住院患者中就有1人发生细菌败血症，死亡率为50%。因此，一种快速、可靠的BSI体外诊断试验将改善患者的预后，并对护理质量、感染控制和整体医疗管理产生可衡量的影响。建议的血流感染(BSI)检测和抗生素敏感性试验(AST)技术具有快速、高灵敏度和需要较低的样本体积。与目前的护理标准(血液培养；BC)相比，该检测方法具有优势，后者通常需要24至72小时才能确认BSI的存在。此外，这种新型的BSI检测不需要复杂的扩增步骤(聚合酶链式反应；聚合酶链式反应)来检测病原体。如果没有适当的抗生素应用，脓毒症死亡率每小时增加7.6%，败血症患者的护理和生存需要早期筛查创新，快速而轻松地对物种进行分型并测定AST，以指导负责任的抗生素使用。与目前的BSI检测方法相关的延迟结果阻碍了有效的抗生素选择、准确性和时机。这项拟议的技术由一项正在申请专利的血液传播病原体浓缩创新组成，该创新结合了功能化磁珠和独特的凝胶(LAL)底物。该检测建立在三个原则上：(1)LAL含有能够检测革兰氏阴性细菌和真菌上的细胞壁标记的高度敏感的蛋白质；(2)不同的LAL阻断将区分真菌和细菌感染；以及(3)包括家蚕幼虫血浆将提供检测革兰氏阳性细菌的比色输出。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。