Molecular Antibiotic Resistance Arrays for clinical microbiology laboratories

描述（由申请人提供）：当前的多药耐药性时代对人类健康、公共卫生和临床医学实践产生了巨大影响。需要改进的技术来为治疗临床医生提供及时和准确的信息，以实现最佳的患者管理。该项目的总体目标是开发、验证和翻译用于临床实验室环境的快速检测和表达阵列，以全面表征临床样本中重要病原体（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。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发生，并改善疾病监测。该阵列将提供病原体检测、抗生素耐药基因/突变的存在和表达标记，以及在适用和相关的情况下，也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现有知识;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;开发针对这些目标的新型PCR检测方法;在高密度格式阵列上单独和一起验证开发的检测方法（使用大型菌株和临床样本库）;开发必要的生物信息学工具，以轻松读取和解释阵列结果;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。小组成员之间先前建立的合作将使拟议活动能够立即实施，并对这一严重威胁产生早期影响。临床医学和公共卫生正面临着常见病原菌多重耐药日益严重的危机。迫切需要更多的信息和快速诊断，为临床医生和公共卫生官员提供必要的信息，以适当应对这些感染。该项目将为五种高度优先的多重耐药病原体开发、验证和转化一个快速高密度抗药性检测系统;这样一个系统将有助于有关抗生素使用的决策，帮助减缓新的抗药性的出现，并改善疾病监测。

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.