An automated, scalable, and rapid AST system for Gonorrhea STIs

用于淋病性传播感染的自动化、可扩展且快速的 AST 系统

基本信息

批准号：
10327731
负责人：
Roy R Swiger
金额：
$ 96.73万
依托单位：
ACENXION BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-15 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10327731
关键词：
Agar Agreement Anatomy Antibiotic Therapy Antibiotic susceptibility Antibiotics Antimicrobial Resistance Bacteria Behavior Carbon Dioxide Categories Centers for Disease Control and Prevention (U.S.)Clinical Clinical Research Code Computer software Computers Contracts Data Data Analyses Development Devices Ensure Environment Feedback Funding Future Genetic Materials Genitourinary system Gonorrhea Growth Healthcare Hospitals Hour Human Human Resources Incidence Intermediate resistance Investments Laboratories Liquid substance Location Manuals Methods Microfluidics Minimum Inhibitory Concentration measurement Molecular Monitor Neisseria gonorrhoeae Optics Organism Patients Phase Phenotype Predisposition Preparation Price Protocols documentation Public Health Reader Reading Recording of previous events Reporting Reproducibility Sampling Savings Sensitivity and Specificity Sexually Transmitted Diseases Single-Blind Study Small Business Innovation Research Grant Speed Spottings Surveillance Program Surveys System Testing Time Work base co-infection commercialization cost design experimental study field study hospital laboratories instrument laboratory facility practical application programs prototype resistance mechanism response success

项目摘要

Gonorrhea is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae (NG) that infects the urogenital, anorectal and pharyngeal tracts in humans. In 2018, there were an estimated 1.14M cases in the US, and 86.9M cases worldwide. Of concern is the growing incidence of antimicrobial resistance not only due to inappropriate use of antibiotics, but also because NG interacts with and acquires genetic material from other co-infections in the anatomical sites that it infects. This wide range of resistance mechanisms that NG isolates can potentially harbor makes it very challenging to develop rapid molecular methods of Antibiotic Susceptibility Testing (AST). Even among phenotypic AST methods, it has so far not been considered feasible to perform automated broth microdilution based ASTs on NG: principally because it is a fastidious organism in liquid culture. As a result, the primary method used to perform ASTs for NG is the manual agar dilution method, which (because it is so labor intensive) is currently conducted in only a very limited number of public health labs. Even these labs test only 200-300 samples a month. Acenxion Biosystems proposes to develop the first fully automated NG phenotypic AST platform that both satisfies the current CDC guidance for surveillance and fulfils an unmet clinical need for AST-guided “directed” antibiotic therapy. Our instrument will provide Minimum Inhibitory Concentration (MIC) and Susceptible/ Intermediate /Resistance (S/I/R) interpretation in < 6 hours with minimal sample preparation (<5 min per sample) at a reasonable price. The instrument will consist of stackable, cassette reader units with up to eight microfluidic cassette capacity; software/PC Controller; and single-use consumable (50-well microfluidic cassette pre-spotted with candidate antibiotics). Optimized broth and rapid stirring are employed for NG growth, enabling automated broth microdilution. With prior funding from the CDC, we have demonstrated proof-of-concept for the proposed instrument by building a partly-automated system to perform broth micro- dilution experiments on a single 16-well cassette, and used it monitor the growth (or lack thereof) of 3 NG strains (1 ATTC QC strain, and 2 AR isolate strains) in the presence of multiple candidate antibiotics with 100% sensitivity & specificity. We seek “Direct to Phase II” funds to expand this earlier work: build a fully automated instrument and test it against the CDC’s challenge AR bank panel of 50 clinical isolates (which span multiple resistance mechanisms and yield wide range of phenotypic responses). We chose this set of organisms in lieu of patient samples from 2 - 3 locations to ensure better chances of success in the real world. Our commercialization strategy aims to first bring efficiencies to the existing market (regional labs participating in the Gonococcal Isolate Survey Program) and then to expand the user (customer) base to hospital labs, clinical laboratory networks and clinical labs by enabling AST-guided directed antibiotic therapy for gonorrhea.

淋病是一种由淋病奈瑟菌 (NG) 引起的性传播感染 (STI)， 2018 年，估计有 114 万例感染人类泌尿生殖道、肛门直肠和咽部。美国有 8690 万例，而全球有 8690 万例，令人担忧的是抗菌素耐药性的发生率不断上升。不仅是由于抗生素使用不当，还因为 NG 与遗传相互作用并获得遗传这种广泛的耐药性。 NG 分离株可能具有的机制使得开发快速分子即使在表型 AST 方法中，迄今为止也还没有。被认为在 NG 上进行基于自动肉汤微量稀释的 AST 是可行的：主要是因为它是液体培养中的一种挑剔的生物体，因此，用于 NG 的 AST 的主要方法是手动琼脂稀释方法（因为它是劳动密集型的）目前仅在非常有限的情况下进行公共卫生实验室数量有限，即使这些实验室每月也只能检测 200-300 个样本。 Acenxion Biosystems 提议开发第一个全自动 NG 表型 AST 平台满足当前 CDC 的监测指南，并满足 AST 引导“定向”的未满足的临床需求我们的仪器将提供最低抑制浓度 (MIC) 和敏感/ 在 < 6 小时内完成中间/电阻 (S/I/R) 解释，只需最少的样品制备（每次<5 分钟）样品）以合理的价格该仪器将由可堆叠的盒式磁带读取器单元组成，最多可容纳八个单元。微流体盒容量；软件/PC 控制器；和一次性耗材（50 孔微流体） NG 时采用优化的肉汤和快速搅拌。借助 CDC 的先前资助，我们已经证明了这一点。通过构建半自动化系统来执行肉汤微量分析，对拟议仪器进行概念验证在单个 16 孔盒上进行稀释实验，并用它监测 3 NG 的生长（或缺乏）存在多种候选抗生素时的菌株（1 个 ATTC QC 菌株和 2 个 AR 分离菌株）我们寻求“直接进入第二阶段”资金来扩展这项早期工作：建立一个全面的项目。自动化仪器，并针对 CDC 的挑战 AR 库小组（由 50 个临床分离株（涵盖多种耐药机制并产生广泛的表型反应）。生物体代替来自 2 - 3 个地点的患者样本，以确保在现实世界中获得更好的成功机会。我们的商业化战略旨在首先提高现有市场的效率（参与的区域实验室）在淋球菌分离调查计划中），然后将用户（客户）基础扩展到医院实验室，通过启用 AST 引导的淋病定向抗生素治疗来建立临床实验室网络和临床实验室。