Molecular Antibiotic Resistance Arrays for clinical microbiology laboratories

用于临床微生物学实验室的分子抗生素耐药性芯片

• 批准号: 8661107
• 负责人: Paul Stephen Keim
• 金额: $ 86.81万
• 依托单位: TRANSLATIONAL GENOMICS RESEARCH INST
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661107
• 关键词: Acinetobacter baumannii; Antibiotic Resistance; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Arizona; Bioinformatics; Biological Assay; Biotechnology; Characteristics; Clinical; Clinical Medicine; Clinical Microbiology; Clinical Trials; Collaborations; Collection; Computer Simulation; Computer software; Data; Data Analyses; Databases; Decision Making; Detection; Development; Diagnostic; Disease; Evaluation; Exhibits; Future; Gene Expression; Gene Mutation; Genes; Genetic Materials; Genomics; Genotype; Goals; Health; Hospitals; Human; Human Resources; In Situ; In Vitro; Infection; Klebsiella pneumonia bacterium; Knowledge; Laboratories; Lead; Libraries; Medical; Microbiological Techniques; Molecular; Molecular Epidemiology; Multi-Drug Resistance; Outcome; Pathogen detection; Patients; Performance; Phenotype; Process; Protocols documentation; Pseudomonas aeruginosa; Public Health; Public Health Practice; Reading; Reporting; Reproducibility; Research; Research Design; Research Institute; Resistance; Running; Sampling; Science; Sensitivity and Specificity; Staging; Staphylococcus aureus; Streptococcus pneumoniae; System; Technology; Testing; Training; Translating; Translational Research; Translations; Update; Validation; Work; base; bench to bedside; clinical application; clinically significant; commercialization; density; design; genome sequencing; improved; member; new technology; novel; pathogen; programs; rapid detection; repository; research clinical testing; screening; success; tool; user-friendly

DESCRIPTION (provided by applicant): The current era of multi-drug resistance is having dramatic impacts on human health, public health and the practice of clinical medicine. Improved technology is needed to provide prompt and accurate information to treating clinicians for best patient management. The overarching goal on this project is to develop, validate and translate a rapid detection and expression array, for the clinical laboratory setting, to comprehensively characterize antibiotic resistance in important pathogens (Pseudomonas aeruginosa, Klebsiella pneumonia, Acinetobacter baumannii, Staphylococcus aureus, and Streptococcus pneumoniae) in clinical samples. Such a system would assist decision-making with respect to antibiotic use, help slow the onset of additional resistance, and improve disease surveillance. This array will provide pathogen detection, markers for presence and expression of antibiotic resistance genes/mutations and, where applicable and pertinent, strain-typing information that can also be used for diagnostic and in-hospital surveillance. The logical flow of the research plan will include capturing all current knowledge on antibiotic resistance characteristics for target pathogens; conducting additional analyses to further knowledge on species signatures and antibiotic resistance characteristics; developing novel PCR assays for these targets; validating developed assays, both individually and together on the high-density format array (using large strain and clinical sample repositories); developing the bioinformatic tools necessary to easily read and interpret array findings; and finally transferring developed technology to a clinical laboratory for evaluation. The project team has expertise from translational research, genomic analysis, clinical-based research, molecular epidemiology, public health and medical biotechnology development. Previously established collaborations among the team members will allow for immediate implementation of the proposed activities and early impacts on this grave threat. Clinical medicine and public health are facing the growing crisis of multi-drug resistance in common pathogens. More informative and rapid diagnostics are urgently needed to provide clinicians and public health officials the information necessary to appropriately respond to these infections. This project will develop, validate and translate a rapid high-density antibiotic-resistance detection system for five high-priority multi-drug resistant pathogens; such a system would assist decision-making with respect to antibiotic use, help slow the onset of additional resistance, and improve disease surveillance.

描述（由申请人提供）：当前的多重耐药性时代正在对人类健康、公共卫生和临床医学实践产生巨大影响。需要改进技术来为治疗临床医生提供及时、准确的信息，以实现最佳的患者管理。该项目的总体目标是开发、验证和转化用于临床实验室环境的快速检测和表达阵列，以全面表征重要病原体（铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌、金黄色葡萄球菌和肺炎链球菌）的抗生素耐药性）在临床样本中。这样的系统将有助于抗生素使用方面的决策，有助于减缓额外耐药性的发生，并改善疾病监测。该阵列将提供病原体检测、抗生素抗性基因/突变存在和表达的标记，以及在适用和相关的情况下，还可用于诊断和院内监测的菌株分型信息。研究计划的逻辑流程将包括获取有关目标病原体抗生素耐药性特征的所有当前知识；进行额外分析，以进一步了解物种特征和抗生素耐药性特征；针对这些目标开发新的 PCR 检测方法；在高密度格式阵列上单独和一起验证开发的测定（使用大型菌株和临床样本存储库）；开发轻松读取和解释阵列结果所需的生物信息工具；最后将开发的技术转移到临床实验室进行评估。该项目团队拥有转化研究、基因组分析、临床研究、分子流行病学、公共卫生和医学生物技术开发方面的专业知识。团队成员之间先前建立的合作将有助于立即实施拟议的活动并尽早对这一严重威胁​​产生影响。临床医学和公共卫生面临着常见病原体日益严重的多重耐药危机。迫切需要提供更多信息和快速诊断，以便为临床医生和公共卫生官员提供适当应对这些感染所需的信息。该项目将为五种高优先级多重耐药病原体开发、验证和转化快速高密度抗生素耐药性检测系统；这样一个系统将有助于抗生素使用方面的决策，有助于减缓额外耐药性的出现，并改善疾病监测。

项目成果

Genomic Analysis of the Emergence and Rapid Global Dissemination of the Clonal Group 258 Klebsiella pneumoniae Pandemic.

克隆群 258 肺炎克雷伯菌大流行的出现和快速全球传播的基因组分析。

• 发表时间: 2015
• 影响因子: 3.7
• 作者: Bowers, Jolene R;Kitchel, Brandon;Driebe, Elizabeth M;MacCannell, Duncan R;Roe, Chandler;Lemmer, Darrin;de Man, Tom;Rasheed, J Kamile;Engelthaler, David M;Keim, Paul;Limbago, Brandi M
• 通讯作者: Limbago, Brandi M

Rapid and robust phylotyping of spa t003, a dominant MRSA clone in Luxembourg and other European countries.

对卢森堡和其他欧洲国家的主要 MRSA 克隆 ​​spa t003 进行快速而稳健的系统发育分析。

• 发表时间: 2013-07-23
• 影响因子: 3.7
• 作者: Engelthaler, David M;Kelley, Erin;Driebe, Elizabeth M;Bowers, Jolene;Eberhard, Carl F;Trujillo, Jesse;Decruyenaere, Frederic;Schupp, James M;Mossong, Joel;Keim, Paul;Even, Jos
• 通讯作者: Even, Jos

Mapping the Evolution of Hypervirulent Klebsiella pneumoniae.

绘制高毒力肺炎克雷伯菌的进化图。

• 发表时间: 2015-07-21
• 影响因子: 6.4
• 作者: Struve, Carsten;Roe, Chandler C;Stegger, Marc;Stahlhut, Steen G;Hansen, Dennis S;Engelthaler, David M;Andersen, Paal S;Driebe, Elizabeth M;Keim, Paul;Krogfelt, Karen A
• 通讯作者: Krogfelt, Karen A

Evolution of a pathogen: a comparative genomics analysis identifies a genetic pathway to pathogenesis in Acinetobacter.

病原体的进化：比较基因组学分析确定了不动杆菌发病机制的遗传途径。

• 发表时间: 2013
• 影响因子: 3.7
• 作者: Sahl, Jason W;Gillece, John D;Schupp, James M;Waddell, Victor G;Driebe, Elizabeth M;Engelthaler, David M;Keim, Paul
• 通讯作者: Keim, Paul

KlebSeq, a Diagnostic Tool for Surveillance, Detection, and Monitoring of Klebsiella pneumoniae.

KlebSeq，一种用于肺炎克雷伯菌监测、检测和监测的诊断工具。

• 发表时间: 2016-10
• 影响因子: 9.4
• 作者: Bowers, Jolene R;Lemmer, Darrin;Sahl, Jason W;Pearson, Talima;Driebe, Elizabeth M;Wojack, Bette;Saubolle, Michael A;Engelthaler, David M;Keim, Paul
• 通讯作者: Keim, Paul