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Novel Methodology for Rapid Antibiotic Susceptibiility Testing in S. aureus

金黄色葡萄球菌快速抗生素敏感性测试的新方法

基本信息

批准号：
7898604
负责人：
Alexis F Sauer-Budge
金额：
$ 14.6万
依托单位：
FRAUNHOFER CENTER /MANUFACTURING INNOV
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-23 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7898604
关键词：
Address Anabolism Antibiotic Resistance Antibiotic Therapy Antibiotic susceptibility Antibiotics Bacteria Bacterial Antibiotic Resistance Bacterial Infections Biological Models Boston Cell Wall Cell membrane Cells Chemicals Clinical Community Healthcare Community-Acquired Infections Culture Media Detection Development Diagnostic Diagnostic Procedure Disease Drug resistance Fluorescence Microscopy Fluorescent Dyes Growth Hospitals Infection Liquid substance Literature Mechanical Stress Membrane Potentials Methicillin Methicillin Resistance Methodology Methods Microbe Modality Monitor Monobactams Multi-Drug Resistance Nature Nosocomial Infections Optics Organism Pathway interactions Patient Noncompliance Pharmaceutical Preparations Pharmacotherapy Phase Photography Physicians Predisposition Prevalence Protein Synthesis Inhibitors Protocols documentation Public Health Regimen Resistance Risk Factors Role Specificity Staging Staining method Stains Staphylococcus aureus Stress Surface System Techniques Testing Time Universities Woman Work antimicrobial base cell injury clinical practice combat fluid flow fluorescence microscope improved innovation medical schools meetings methicillin resistant Staphylococcus aureus novel novel diagnostics pathogen pathogenic bacteria public health relevance rapid detection repair enzyme repaired resistant strain shear stress sobriety statistics trend

项目摘要

DESCRIPTION (provided by applicant): The emergence of bacterial resistance to antibiotics continues to be a significant public health challenge. Factors contributing to the rise in antibiotic resistance include widespread and inappropriate prescription of broad spectrum antibiotics and patient non-compliance to antibiotic regiments. The healthcare community is responding by limiting antibiotics and prescribing targeted narrow-spectrum antimicrobial therapies when possible. Meanwhile, current antimicrobial development is focused more and more on narrow-spectrum drugs. To enable the effective use of antimicrobial therapy, new methods for detection of antibiotic susceptibility must be developed that enable physicians to prescribe these narrow spectrum antibiotics as close to initial examination as possible. Here, we propose to investigate a novel mechanism that would be the basis for a diagnostic to meet this important public health need. In this R21 application, Dr. Alexis Sauer-Budge at the Fraunhofer Center for Manufacturing Innovation at Boston University and Dr. Jean Lee of Brigham and Women's Hospital and Harvard Medical School have teamed up to explore the hypothesis that mechanical stress on bacteria will damage the cell wall and rapidly initiate cell wall repair biosynthesis pathways. In the presence of antibiotics targeted at cell wall biosynthesis, susceptible strains will be unable to recover from the damage and will die, whereas resistant strains will recover. The susceptibility of the bacteria can therefore be determined rapidly via fluorescence microscopy when the mechanical stress is applied in the presence of fluorescent dyes which stain the damaged bacteria. We propose to investigate this hypothesis by building a flow cell and optical apparatus, varying experimental conditions to optimize the protocol for antibiotic susceptibility detection, and quantify the variability due to different strains and growth phases of the bacteria. We propose to use the model system of Staphylococcus aureus, both methicillin-susceptible and methicillin- resistant strains. If successful, we anticipate this methodology will be applicable to a wide range of bacteria and antibiotics of various mechanisms of action. PUBLIC HEALTH RELEVANCE: The increasing prevalence of multi-drug resistant bacterial infections is a growing public health problem. To combat the trend and to fully enable physicians to prescribe appropriate antimicrobial therapy, new rapid diagnostic methods for antibiotic susceptibility must be developed. Here, we propose to address the gap in antibiotic susceptibility diagnostics by developing a novel technique for rapid detection of antibiotic susceptibility using Staphylococcus aureus as our model system.

描述(由申请人提供)：细菌对抗生素的耐药性的出现仍然是一个重大的公共卫生挑战。导致抗生素耐药性上升的因素包括广谱抗生素的广泛和不适当的处方以及患者不遵守抗生素方案。医疗界正在做出回应，限制抗生素，并在可能的情况下开出有针对性的窄谱抗菌疗法。与此同时，目前抗菌药物的开发越来越集中在窄谱药物上。为了能够有效地使用抗菌药物治疗，必须开发新的抗生素敏感性检测方法，使医生能够在尽可能接近初始检查的情况下开出这些窄谱抗生素。在这里，我们建议研究一种新的机制，该机制将作为诊断的基础，以满足这一重要的公共卫生需求。在这项R21应用中，波士顿大学弗劳恩霍夫制造创新中心的Alexis Sauer-Budge博士与布里格姆妇女医院和哈佛医学院的Jean Lee博士合作，探索了细菌受到机械压力会破坏细胞壁并迅速启动细胞壁修复生物合成途径的假设。在针对细胞壁生物合成的抗生素存在下，敏感菌株将无法从损害中恢复并将死亡，而耐药菌株将恢复。因此，当机械应力在荧光染料存在的情况下对受损细菌进行染色时，可以通过荧光显微镜快速确定细菌的敏感性。我们建议通过建立流动池和光学装置来研究这一假设，改变实验条件来优化抗生素敏感性检测的协议，并量化不同菌株和细菌生长阶段的变异性。我们建议使用金黄色葡萄球菌的模型系统，既有甲氧西林敏感菌株，也有甲氧西林耐药菌株。如果成功，我们预计这种方法将适用于广泛的细菌和抗生素的各种作用机制。公共卫生相关性：多重耐药细菌感染的日益流行是一个日益严重的公共卫生问题。为了对抗这一趋势，并充分使医生能够开出适当的抗菌药物治疗，必须开发新的抗生素敏感性快速诊断方法。在这里，我们建议通过开发一种以金黄色葡萄球菌为模型系统的快速检测抗生素敏感性的新技术来解决抗生素敏感性诊断方面的空白。