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）：该项目称为“耐药革兰氏阴性病原体检测联盟”，是一个学术-工业合作伙伴关系，旨在解决RFA“诊断合作伙伴关系，以解决选定细菌病原体的抗菌素耐药性”所带来的挑战。该项目将重点关注两组革兰氏阴性菌（GNB）病原体--耐碳青霉烯类肠杆菌科（CRE）和耐药铜绿假单胞菌（PA），这两组病原体已分别被美国疾病控制和预防中心（CDC）指定为“紧急威胁”和“严重威胁”病原体。这些微生物是医疗保健相关感染（HAI）的主要原因，但克雷斯也成为社区发病感染（COI）的威胁生命的原因。它们的治疗非常复杂，特别是当它们表达的酶（β-内酰胺酶）与常用的抗菌药物不同时。该项目将开发和验证一个综合诊断系统，用于直接检测和区分GNB与血液和尿液样本中的克雷斯和PA。同样的系统将被设计用于检测所有临床上重要的β-内酰胺酶，以便临床医生能够对启动哪种抗生素做出更明智和快速的决定。因此，集成系统被设计为在一个设备中模拟临床微生物学实验室中检测克雷斯和PA所涉及的大多数步骤。由于两个重要的创新，拟议的诊断系统成为可能。一个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用于物种鉴定。另一种称为自加速二聚化（SAD）测定，其促进细菌酶扩增，使得可以在不到10分钟内检测到目标酶活性。SAD检测试剂盒将整合到iMDx中。总之，这些创新将针对从世界不同地区的血流（BSI）和尿路感染（UTI）中获得的大量GNB临床分离株进行改进和验证。还将在San弗朗西斯科总医院对因BSI或败血症以及导管相关UTI住院的患者进行前瞻性评估。该系统的成功开发不仅将改善患者的临床管理，而且有助于减少昂贵的新一代抗生素的不必要使用，并防止在医疗保健和社区环境中选择新的耐药性GNB病原体。