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

这项小型企业创新研究（SBIR）I期项目的更广泛影响/商业潜力将建立一种快速，灵敏的病原体分型和血流感染（BSI）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将减少败血症的发生率，以及不必要或不适当的抗生素给药，这可能导致病原体突变和抗菌素耐药性（AMR）。COVID-19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AMR的威胁，特别是考虑到每7名COVID-19住院患者中就有1名发生细菌性败血症，死亡率为50%。因此，一个快速，可靠的体外诊断测试BSI将改善患者的结果，并有一个可衡量的影响，护理质量，感染控制和整体healthcare management.The拟议的技术血流感染（BSI）检测和抗生素敏感性测试（AST）是快速，高灵敏度，并需要一个低样本量。该测定将提供优于当前护理标准（血液培养; BC）的优点，其通常需要24至72小时来确认BSI的存在。此外，这种新型BSI检测不需要复杂的扩增步骤（聚合酶链反应; PCR）来检测病原体。鉴于脓毒症死亡率每小时增加7.6%，如果没有适当的抗生素管理，脓毒症患者的护理和生存需要早期筛查创新，快速，轻松地分型物种和确定AST，以指导负责任的抗生素管理。与当前BSI测试方法相关的延迟结果阻碍了有效的抗生素选择，准确性和时间。该技术由正在申请专利的血源性病原体富集创新组成，该创新结合了功能化磁珠和独特的鲎变形细胞溶解物（LAL）基质。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物的高度敏感的蛋白质;（2）鉴别LAL阻断将区分真菌和细菌感染;和（3）蚕幼虫血浆的包含将提供检测克-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 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.