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Microfluidic platform for stress-induced rapid antibiotic susceptibility testing

用于应激诱导快速抗生素敏感性测试的微流控平台

基本信息

批准号：
9264397
负责人：
Maxim Kalashnikov
金额：
$ 39.62万
依托单位：
FRAUNHOFER CENTER /MANUFACTURING INNOV
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-17 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9264397
关键词：
Address Aminoglycosides Anabolism Antibiotic Resistance Antibiotic Therapy Antibiotic susceptibility Antibiotics Bacteria Bacterial Infections Biochemical Pathway Biological Assay Biological Models Cell Death Cell Wall Cells Ciprofloxacin Clindamycin Clinical Clinical Microbiology Combined Antibiotics Communicable Diseases Complement Consult DNA Daptomycin Data Diagnostic Procedure Disease Drug resistance Effectiveness Enzymes Erythromycin Evaluation Funding Generations Genetic Transcription Genetic screening method Goals Government Gram-Negative Bacteria Gram-Positive Bacteria Growth High Prevalence Ionic Strengths Laboratories Lead Literature Mechanical Stress Mechanics Methicillin Methicillin Resistance Methodology Methods Microbe Microfluidics Minimum Inhibitory Concentration measurement Monitor Multi-Drug Resistance Organism Oxidative Stress Pathway interactions Patient Noncompliance Patients Pattern Performance Persons Pharmacotherapy Phenotype Physicians Predisposition Prevalence Process Proliferating Protein Biosynthesis Public Health Publishing Reagent Regimen Reporter Research Resistance Sampling Scientist Specificity Specimen Staphylococcus aureus Stress Sulfonamides System Techniques Technology Testing Tetracyclines Time Vancomycin Work bacterial metabolism bactericide base beta-Lactams biological adaptation to stress clinical diagnostics clinical practice combat cost drug candidate epidemiology study experimental study field study improved innovation killings molecular diagnostics new technology novel novel diagnostics pathogen public health relevance rapid detection rapid technique repaired resistance mechanism resistant strain response screening shear stress skills stressor success tool treatment choice trend

项目摘要

DESCRIPTION (provided by applicant): Current standard methods for detecting antibiotic susceptibility are based on the ability of the bacteria to proliferate in the presence of antibiotis, and thus these techniques are time-consuming, costly, and insensitive, particularly for evaluation of slow-growing organisms. To develop a truly rapid susceptibility test, one must circumvent the need for growth. We are developing a microfluidic test that interrogates the response of cells to antibiotics in the presence of mechanical and/or soluble stressors and thereby minimizes the time to results. The core of the hypothesis is that by straining the cell, we induce the cellular repair processes and associated biochemical pathways. These pathways are often targets of antibiotics (e.g., cell wall biosynthesis, protein synthesis, DNA transcription). f the antibiotic hinders those repair processes, the cell will die under the continued application of stress. We posit that monitoring cell death under stress in the presence of antibiotics can provide phenotypic information in an ultra-rapid time frame allowing physicians to make appropriate antibiotic treatment choices sooner. We envisage that this methodology would complement the existing rapid tests based on molecular diagnostics (e.g., PCR) because it would provide a low-cost rapid method that delivers phenotypic information. While genetic tests provide precise information for epidemiological studies, the high reagent costs, relatively high operator skills required, and limited clinical utility continue to limit widespread routine use. Furthermore, the molecular diagnostics suffer from a high number of false positives and unacceptable performance in non-sterile specimens (e.g., polymicrobial samples). As our method could be automated and is based on phenotypic changes, we believe it is superior as a routine clinical diagnostic providing physicians with the information they need to treat their patients, namely what antibiotic to use to kill the infecting pathogen. The method can be multiplexed (multiple antibiotics and multiple organisms) and can be integrated with current bacterial identification methodologies, thus it has the potential to be the basis of a new diagnostics system that rapidly provides clinicians with both identification and antibiotic susceptibility profiles in a timeframe that is much shorter than is currently possible. The method also opens new avenues of research into how stress can potentiate the effects of antibiotics. Once developed, the technique could also be used as a rapid screening technology for new antibiotic drug candidates.

描述（由申请人提供）：目前检测抗生素敏感性的标准方法是基于细菌在抗生素存在下增殖的能力，因此这些技术耗时，昂贵且不敏感，特别是对于缓慢生长的生物体的评估。要开发一种真正快速的敏感性测试，就必须避开对生长的需求。我们正在开发一种微流体测试，可以在机械和/或可溶性压力源存在的情况下询问细胞对抗生素的反应，从而最大限度地缩短获得结果的时间。这个假说的核心是，通过使细胞紧张，我们