Antimicrobial Synergy for Carbapenem-Resistant Enterobacteriaceae - Administrative Supplement

耐碳青霉烯类肠杆菌科细菌的抗菌协同作用 - 行政补充

• 批准号: 10117330
• 负责人: Thea Brennan-Krohn
• 金额: $ 2.79万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-20 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117330
• 关键词: Administrative Supplement; Advisory Committees; Antibiotic Therapy; Antimicrobial susceptibility; Award; Biological Assay; Childhood; Clinical; Clinical Research; Clinical Trials; Collection; Combined Antibiotics; Communicable Diseases; Data; Detection; Development; Enterobacteriaceae Infections; Fellowship; Frequencies; Funding; Goals; Immunocompromised Host; In Vitro; Investigation; Israel; Kinetics; Laboratories; Master of Science; Medical Microbiology; Medical center; Mentorship; Methods; Modality; Parents; Patient Care; Patients; Pharmacology; Postdoctoral Fellow; Principal Investigator; Research; Research Personnel; Research Project Grants; Resistance; System; Technology; Testing; Thea Plant; Time; Translational Research; United States National Institutes of Health; antimicrobial; bactericide; base; carbapenem resistance; carbapenem-resistant Enterobacteriaceae; career; clinically actionable; combinatorial; design; drug resistant bacteria; improved; in vivo; instructor; interest; medical schools; mouse model; novel; novel diagnostics; novel therapeutics; pathogen; pharmacokinetics and pharmacodynamics; prospective; synergism

Project Summary/Abstract – Parent K08 The proposed project is an investigation of the synergistic activity of antimicrobial combinations against carbapenem-resistant Enterobacteriaceae (CRE). The principal investigator, Dr. Thea Brennan-Krohn, recently completed fellowships in Pediatric Infectious Diseases and in Medical Microbiology and is now an Instructor at Harvard Medical School and a post-doctoral fellow at Beth Israel Deaconess Medical Center. She is interested in improving methods for detection and characterization of antimicrobial synergy in order to guide the treatment of patients infected with highly resistant pathogens. Her career goal is to become a leading investigator in the development, implementation and interpretation of tests for detection of antimicrobial synergy. During the award period, she will obtain a Master of Science in Pharmacology and will pursue coursework in clinical and translational research. The proposed research will be carried out under the mentorship of James Kirby, MD, D(ABMM), an NIH-funded investigator at Beth Israel Deaconess Medical Center whose laboratory investigates topics highly relevant to the proposed project, including the development of novel antimicrobial susceptibility testing methods and the investigation of new therapeutics for CRE. Dr. Brennan-Krohn will be supported during the award period by an advisory committee that includes Dr. George Eliopoulos, a world-renowned expert on antimicrobial synergy. In the proposed project, Dr. Brennan-Krohn will initially test antimicrobial combinations against a comprehensive collection of clinical CRE isolates in order to establish combinatorial spectra of activity. For this part of the project, she will use an automated checkerboard array microdilution method that makes use of the HP D300 inkjet printer-based dispensing system. She will next develop a novel, fluorescent time-kill synergy assay in order to investigate the bactericidal kinetics of synergistic combinations. Finally, she will investigate the in vivo efficacy and PK/PD parameters of the most effective combinations using an immunocompromised mouse model of CRE infection. Ultimately, the enhanced understanding of synergy as well as the technology developed and validated during the proposed study are expected to inform the design of prospective clinical trials of combination antibiotic therapy and to establish simple, rapid synergy testing platforms that will for the first time provide synergy data that can be used in a clinically actionable timeframe to guide patient care.

项目摘要/摘要-父K08 拟议的项目是研究抗菌剂组合的协同活性。 抗碳青霉烯类耐药肠杆菌科(CRE)。首席调查员，西娅博士 Brennan-Krohn，最近完成了儿科传染病和医学方面的研究员 他现在是哈佛医学院的讲师和哈佛大学的博士后研究员 贝丝以色列女执事医疗中心。她对改进检测和检测的方法感兴趣 表征抗菌药物的协同作用以指导感染患者的治疗 高度耐药的病原体。她的职业目标是成为一名顶尖的调查员 制定、实施和解释检测抗菌剂协同作用的测试。 在授勋期间，她将获得药理学硕士学位，并将继续 临床和转化性研究的课程。拟议的研究将在以下情况下进行 詹姆斯·柯比医学博士(ABMM)的指导，他是美国国立卫生研究院资助的贝丝以色列研究所的研究员 女执事医疗中心，其实验室调查与拟议的 项目，包括开发新的抗菌素敏感性测试方法和 慢性肾衰新疗法的研究。布伦南-克罗恩博士将在颁奖期间得到支持 期间由一个咨询委员会提出，该委员会成员包括世界著名专家乔治·埃利奥普洛斯博士 关于抗菌剂的协同作用。在拟议的项目中，Brennan-Krohn博士将首先测试抗菌剂 针对临床Cre分离株的全面收集进行组合，以建立 活度的组合光谱。对于该项目的这一部分，她将使用自动化的 一种利用HP D300喷墨打印机为基础的棋盘阵列微量稀释方法 配药系统。她接下来将开发一种新的荧光时间消磨协同试验，以便 研究增效复配的杀菌动力学。最后，她将调查内幕 使用AN的最有效组合的体内疗效和PK/PD参数 免疫功能低下的Cre感染小鼠模型。归根结底，对 协同效应以及在拟议研究期间开发和验证的技术是 预计将为抗生素联合治疗和联合治疗的前瞻性临床试验的设计提供信息 建立简单、快速的协同测试平台，首次提供协同数据 这可以在临床上可操作的时间框架内用于指导患者护理。