Consortium for drug-resistant Gram-negative pathogen detection

耐药革兰氏阴性病原体检测联盟

• 批准号: 8876481
• 负责人: Luke P. Lee
• 金额: $ 115.41万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-10 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8876481
• 关键词: Address; Antibiotics; Antimicrobial Resistance; Bacteria; Biological Assay; Biomedical Engineering; Blood; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Management; Clinical Microbiology; Communicable Diseases; Communities; Detection; Development; Devices; Diagnostic; Diagnostic tests; Dimerization; Drug resistance; Enterobacteriaceae; Enzymes; Escherichia coli; Family; General Hospitals; Generations; Glucose; Healthcare; Hospitals; Hour; Immunoassay; Infection; Institution; Laboratories; Lactamase; Lactams; Lactose; Lead; Life; Methods; Microfluidics; Molecular; Monoclonal Antibodies; Multi-Drug Resistance; Organism; Outcome; Pathogen detection; Patients; Pharmaceutical Preparations; Predictive Value; Preparation; Pseudomonas aeruginosa; Reagent; Research; Research Personnel; Resistance profile; Sampling; San Francisco; Sensitivity and Specificity; Sepsis; Silver; Solutions; Stream; System; Systems Development; Techniques; Technology; Testing; Urinary tract infection; Urine; antimicrobial drug; base; beta-Galactosidase; carbapenem-resistant Enterobacteriaceae; catheter associated UTI; chromophore; clinical practice; community setting; design; disorder prevention; drug resistant bacteria; enzyme activity; improved; innovation; novel; novel diagnostics; pathogen; polyclonal antibody; prevent; public health relevance

 DESCRIPTION (provided by applicant): This project called "Consortium for drug-resistant Gram-negative pathogen detection" is an academic-industrial partnership established to address the challenges posed by the RFA "Partnerships for Diagnostics to Address Antimicrobial Resistance of Select Bacterial Pathogens". The project will focus on two groups of Gram-negative bacterial (GNB) pathogens-carbapenem-resistant Enterobacteriaceae (CRE) and drug-resistant Pseudomonas aeruginosa (PA), which have been designated by the Centers for Disease Control and Prevention (CDC) as "urgent threat" and "serious threat" pathogens, respectively. These organisms are major causes of healthcare-associated infections (HAIs), but CREs are also emerging as life-threatening causes of community-onset infections (COIs). They are enormously complicated to treat, especially when they express enzymes (ß-lactamases) that inactivate commonly-used antimicrobial agents. This project will develop and validate an integrated diagnostic system designed to directly detect and differentiate GNBs into CREs and PA from blood and urine samples. The same system will be designed to detect all of the clinically important ß- lactamases, so that clinicians can make a more informed and rapid decision about which antibiotics to initiate. The integrated system is thus designed to mimic in one device most of the steps involved in a clinical microbiology laboratory to detect CREs and PA. The proposed diagnostic system is made possible because of two important innovations. One is an integrated molecular diagnostics system (iMDx) designed to rapidly separate GNBs from clinical sample and capture target GNBs for species identification. The other is called self-accelerated dimerization (SAD) assay that facilitates bacterial enzyme amplification so that the target enzyme activity can be detected in less than 10 minutes. The SAD assay will be integrated into iMDx. Together, these innovations will be refined and validated against a large panel of clinical isolates of GNBs obtained from blood stream (BSI) and urinary tract infections (UTI) in different regions of the world. The accuracy of the system will also be prospectively assessed at San Francisco General Hospital among patients hospitalized for BSI or sepsis, and catheter-associated UTI. A successful development of this system will not only improve patient clinical management, but help reduce unnecessary use of expensive, later-generation antibiotics and prevent the selection of new drug-resistant GNB pathogens in healthcare and community settings.

 描述（由申请人提供）：这个名为“耐药革兰氏阴性病原体检测联盟”的项目是一个学术-工业合作伙伴关系，旨在解决 RFA“解决选定细菌病原体抗菌素耐药性的诊断合作伙伴关系”提出的挑战该项目将重点关注两类革兰氏阴性细菌（GNB）病原体——耐碳青霉烯类肠杆菌科（CRE）和耐药细菌铜绿假单胞菌 (PA) 已被疾病控制和预防中心 (CDC) 分别指定为“紧急威胁”和“严重威胁”病原体，这些生物体是医疗保健相关感染 (HAI) 的主要原因，但是。 CRE 也正在成为社区发病感染 (COIs) 的危及生命的原因，它们的治疗极其复杂，特别是当它们表达的酶（β-内酰胺酶）会灭活常用的酶时。该项目将开发和验证一个集成诊断系统，该系统旨在直接检测血液和尿液样本中的 GNB 并将其区分为 CRE 和 PA。因此，集成系统旨在在一个设备中模拟临床微生物实验室检测 CRE 和 PA 所涉及的大部分步骤，从而做出更明智的决定。其中一项是集成分子诊断系统 (iMDx)，旨在从临床样本中快速分离 GNB 并捕获目标 GNB 以进行物种鉴定；另一个称为自加速二聚化 (SAD) 检测，可促进细菌酶扩增，从而SAD 检测将在不到 10 分钟内被整合到 iMDx 中，这些创新将针对从 GNB 中获得的大量临床分离株进行完善和验证。旧金山综合医院还将在因 BSI 或脓毒症以及导管相关 UTI 住院的患者中对该系统的准确性进行前瞻性评估。该系统的开发不仅将改善患者的临床管理，而且有助于减少不必要地使用昂贵的新一代抗生素，并防止在医疗保健和社区环境中选择新的耐药 GNB 病原体。