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（由应用程序提供）：该项目称为“抗药革兰氏阴性病原体的财团”是一种学术工业伙伴关系，旨在应对RFA的诊断伙伴关系的挑战，以解决精选细菌病原体的抗菌素抵抗的诊断。该项目将集中于两组革兰氏阴性细菌（GNB）病原体 - 碳苯甲酸苯甲酸甲曲科（CRE）（CRE）和耐药性假单胞菌（PA），这些中心已被疾病控制和预防（CDC）指定为“紧急威胁”的“紧急威胁”，这些中心是“严重威胁”和“严重威胁”和“严重的”和“ pathers”和“又有”的恋爱。这些生物是医疗保健相关感染（HAI）的主要原因，但CRE也随着危及生命的社区发作感染（COIS）而出现。它们的治疗非常复杂，尤其是当它们表达酶（ß-内乳酶）灭活常用抗菌剂时。该项目将开发并验证旨在直接检测和将GNB与血液和尿液样本的PA中的GNB直接分化的综合诊断系统。该系统将旨在检测所有临床上重要的β-内酰胺酶，以便临床医生可以对要启动哪种抗生素做出更加明智和快速的决定。因此，集成系统的设计旨在模仿一种设备，其中大多数涉及临床微生物实验室的步骤检测CRES和PA。由于两项重要的创新，提出的诊断系统成为可能。一种是一种综合分子诊断系统（IMDX），旨在快速将GNB与临床样本分开，并捕获目标GNB进行物种鉴定。另一种称为自加二聚化（SAD）测定，促进细菌酶扩增，因此可以在不到10分钟的时间内检测到靶酶活性。 SAD测定法将集成到IMDX中。总之，这些创新将得到完善并证实从世界各个区域中从血流（BSI）和尿路感染（UTI）获得的大量GNB临床分离株进行验证。该系统的准确性也将在旧金山总医院在住院的BSI或败血症以及与导管相关的UTI中评估。该系统的成功开发不仅将改善患者的临床管理，而且有助于减少不必要的使用昂贵的，后期的抗生素，并防止在医疗保健和社区环境中选择耐药的GNB病原体。