Quach D T, Sakoulas G, Nizet V, Pogliano J, Pogliano K
Department of Bioengineering, University of California, San Diego La Jolla, CA, USA; Division of Biological Sciences, University of California, San Diego La Jolla, CA, USA.
Division of Pediatric Pharmacology & Drug Discovery, University of California, San Diego La Jolla, CA, USA.
EBioMedicine. 2016 Jan 18;4:95-103. doi: 10.1016/j.ebiom.2016.01.020. eCollection 2016 Feb.
Successful treatment of bacterial infections requires the timely administration of appropriate antimicrobial therapy. The failure to initiate the correct therapy in a timely fashion results in poor clinical outcomes, longer hospital stays, and higher medical costs. Current approaches to antibiotic susceptibility testing of cultured pathogens have key limitations ranging from long run times to dependence on prior knowledge of genetic mechanisms of resistance. We have developed a rapid antimicrobial susceptibility assay for Staphylococcus aureus based on bacterial cytological profiling (BCP), which uses quantitative fluorescence microscopy to measure antibiotic induced changes in cellular architecture. BCP discriminated between methicillin-susceptible (MSSA) and -resistant (MRSA) clinical isolates of S. aureus (n = 71) within 1-2 h with 100% accuracy. Similarly, BCP correctly distinguished daptomycin susceptible (DS) from daptomycin non-susceptible (DNS) S. aureus strains (n = 20) within 30 min. Among MRSA isolates, BCP further identified two classes of strains that differ in their susceptibility to specific combinations of beta-lactam antibiotics. BCP provides a rapid and flexible alternative to gene-based susceptibility testing methods for S. aureus, and should be readily adaptable to different antibiotics and bacterial species as new mechanisms of resistance or multidrug-resistant pathogens evolve and appear in mainstream clinical practice.
成功治疗细菌感染需要及时给予适当的抗菌治疗。未能及时启动正确的治疗会导致临床结果不佳、住院时间延长和医疗成本增加。目前对培养病原体进行抗生素敏感性测试的方法存在关键局限性，从检测时间长到依赖对抗生素耐药遗传机制的先验知识。我们基于细菌细胞学分析（BCP）开发了一种针对金黄色葡萄球菌的快速抗菌药敏试验，该试验使用定量荧光显微镜来测量抗生素诱导的细胞结构变化。BCP在1 - 2小时内以100%的准确率区分了71株金黄色葡萄球菌的甲氧西林敏感（MSSA）和耐药（MRSA）临床分离株。同样，BCP在30分钟内正确区分了20株金黄色葡萄球菌的达托霉素敏感（DS）和达托霉素不敏感（DNS）菌株。在MRSA分离株中，BCP进一步鉴定出两类对β - 内酰胺抗生素特定组合敏感性不同的菌株。BCP为金黄色葡萄球菌的基于基因的药敏测试方法提供了一种快速且灵活的替代方法，并且随着新的耐药机制或多重耐药病原体在主流临床实践中出现和演变，应该很容易适应不同的抗生素和细菌种类。
Zotero 插件
