Real-Time High Resolution Method for Genomic Surveillance of ESKAPE pathogens

项目概要/摘要 抗生素耐药性是最突出的公共卫生威胁之一。抗生素耐药性的负担是 急剧增加。由抗生素抗性细菌引起的感染是发病的重要原因， 死亡率，尤其是免疫功能低下的患者和老年人。及时预防和治疗感染 抗生素耐药病原体引起的疾病越来越紧迫。 抗生素耐药病原体的基因组监测已成为确定来源的流行病学工具 并追踪由抗生素耐药性病原体引起的感染的传播途径，以控制感染， 评估抗生素耐药性以进行抗生素管理。我们认为，通过例行使用这种 医院的基因组病原体监测系统将是临床医学的革命性成果， 医院更安全然而，目前基于基因组的监测方法还不够快， 周转时间和歧视的权力，作为有效和负责任的翻译方法， 耐抗生素病原体。 为了填补这一空白，我们将开发一个监测系统，该系统具有两个实时基因组感染应用程序 控制和抗生素管理，重点是ESKAPE，高毒力和抗生素耐药细菌 病原体，屎肠球菌，金黄色葡萄球菌，肺炎克雷伯菌，鲍曼不动杆菌， 铜绿假单胞菌和肠杆菌属。拟议的研究将是第一次尝试， 实时基因组监测，可以在医院全面实施和定期使用。拟议 应用程序将允许早期检测传播事件和有针对性的干预措施，以防止传播 抗生素耐药性感染，并帮助治疗困难的感染，补充抗生素管理 努力，降低成本。

PROJECT SUMMARY/ABSTRACT Antibiotic resistance is one of the most prominent public health threats. The burden of antibiotic resistance is drastically increasing. Infections caused by antibiotic resistant bacteria are a significant cause of morbidity and mortality especially in immunocompromised patients and elderly. Timely prevention and treatment of infections caused by antibiotic resistant pathogens are gaining urgency. Genomic surveillance of antibiotic resistant pathogens has emerged as an epidemiology tool to identify sources and track transmission routes of infections caused by antibiotic resistant pathogens for infection control and to evaluate antibiotic resistance for antibiotic stewardship. We believe that the adoption of routine use of such a genomic pathogen surveillance system in hospitals would be revolutionary in clinical medicine and help make hospitals safer places. However, the current genome-based surveillance methods do not have fast enough turnaround time and discriminatory power to serve as the effective and responsible translational methods of antibiotic resistant pathogens. To fill this gap, we will develop a surveillance system with the two real-time genomic applications for infection control and antibiotic stewardship focusing on ESKAPE, highly virulent and antibiotic resistant bacterial pathogens, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. The proposed study will be the first attempt allowing for real-time genomic surveillance which could be fully implemented and regularly used at hospitals. The proposed applications will allow early detection of transmission events and targeted interventions to prevent transmissions of antibiotic resistance infections and help in treatment of difficult infections supplementing antibiotic stewardship efforts, and cost reductions.