PA21259, SBIR, Phase I, Development of a rapid, direct from blood, phenotypic antimicrobial susceptibility assay

PA21259，SBIR，第一阶段，开发快速、直接来自血液的表型抗菌药物敏感性测定

• 批准号: 10602780
• 负责人: Lorenzo Damico
• 金额: $ 30.65万
• 依托单位: AINCOBIO LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2024-08-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10602780
• 关键词: PA21259; SBIR; Phase; Development; rapid

PROJECT SUMMARY Early treatment with effective antibiotics significantly improves clinical outcomes associated with bloodstream infection. However, the phenotypic antimicrobial susceptibility tests (AST) required to choose the right antibiotics take 4-24 hours (often longer in practice) following a 24–48-hour culture, which significantly exceeds the window within which treatment must begin to avoid mortality. The only FDA-cleared rapid AST takes 7 hours; however, it can only be used on a single patient sample following culture and is prohibitively expensive for many institutions, limiting its broad adoption and reducing its clinical impact. Thus, there is an urgent need for a scalable and affordable phenotypic AST that can quickly obtain the drug-resistance profile for microbial pathogens directly from blood, without first requiring a long culturing step. Aincobio is developing a novel phenotypic AST, AST- Shift, that applies macro-and microscale physics to exploit the biophysical properties of microbes to detect response to antimicrobials within one hour following pathogen identification. The AST-Shift device will be an automated, culture-independent, easy-to-use benchtop instrument that will produce a quantitative analysis of antimicrobial response. It is broadly applicable to all bacterial and fungal pathogens, is compatible with downstream applications such as subculture or molecular analysis, and has a small footprint. This Phase I aims to demonstrate proof-of-concept that Aincobio’s AST assay can rapidly and accurately analyze whole blood samples to report on drug-resistance profiles for a number of pathogens (gram-negative, gram-positive, and fungi) treated with different classes of antimicrobial drugs that target bacterial cell walls (vancomycin and meropenem), protein synthesis (linezolid, a bacteriostatic drug), DNA synthesis (ciprofloxacin), and fungal cell walls (flucanozale) and membrane (micafungin). Successful completion of Phase I will de-risk a Phase II project focused on producing single-use multi-well test devices, building a mechanical optical system capable of automatically imaging pathogens in 48 different drug dose channels in parallel, and correlating AST-Shift results with established CLSI clinical breakpoints of ESKAPE and other common pathogens to support a validation study prior to regulatory submission. By reducing the time to phenotypic AST results of confirmed infection we will reduce the time to targeted treatment, with the possibility of enabling truly transformative results when combined with future culture-independent rapid pathogen detection and ID technologies. Aincobio’s simple, cost- effective device will empower physicians with rapid and actionable data to support targeted treatment and improve antimicrobial stewardship efforts.

项目摘要 有效抗生素的早期治疗可显著改善与血流相关的临床结局 感染然而，表型药敏试验（AST）需要选择正确的抗生素 在24-48小时培养后需要4-24小时（实践中通常更长），这大大超过了窗口期 必须在其中开始治疗以避免死亡。唯一FDA批准的快速AST需要7小时;然而， 它只能用于培养后的单个患者样本， 机构，限制其广泛采用并减少其临床影响。因此，迫切需要一种可扩展的 和经济实惠的表型AST，可直接快速获得微生物病原体的耐药性谱 从血液中，而不需要首先进行长时间的培养步骤。Aincobio正在开发一种新的表型AST，AST- 转移，应用宏观和微观物理学来利用微生物的生物物理特性来检测 病原体鉴定后1小时内对抗菌剂的反应。AST-Shift设备将是一个 自动化，培养独立，易于使用的台式仪器，将产生定量分析， 抗菌反应它广泛适用于所有细菌和真菌病原体， 该技术可用于下游应用，如继代培养或分子分析，并且占地面积小。第一阶段旨在 证明Aincobio的AST检测可以快速准确地分析全血 用于报告多种病原体（革兰氏阴性、革兰氏阳性和 真菌）用靶向细菌细胞壁的不同种类的抗微生物药物（万古霉素和 美罗培南）、蛋白质合成（利奈唑胺，一种抑菌药物）、DNA合成（环丙沙星）和真菌细胞 壁（氟氰脲嘧啶）和膜（米卡芬净）。第一阶段的成功完成将降低第二阶段项目的风险 专注于生产一次性多井测试装置，构建能够 并行自动对48个不同药物剂量通道中的病原体进行成像，并将AST偏移结果关联起来 ESKAPE和其他常见病原体的既定CLSI临床折点，以支持验证 在监管提交之前进行研究。通过减少确认感染的表型AST结果的时间， 将缩短靶向治疗的时间，并有可能实现真正的变革性结果， 结合未来的非培养快速病原体检测和ID技术。安科比奥很简单，成本- 有效设备将使医生能够获得快速和可操作的数据，以支持有针对性的治疗， 改进抗菌剂管理工作。