Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, UK.
Int J Antimicrob Agents. 2012 Feb;39(2):96-104. doi: 10.1016/j.ijantimicag.2011.09.028. Epub 2011 Dec 21.
Meticillin-resistant Staphylococcus aureus (MRSA) remains one of the principal multiply resistant bacterial pathogens causing serious healthcare-associated and community-onset infections. This paper reviews recent studies that have elucidated the virulence strategies employed by MRSA, key clinical trials of agents used to treat serious MRSA infections, and accumulating data regarding the implications of antibacterial resistance in MRSA for clinical success during therapy. Recent pre-clinical data support a species-specific role for Panton-Valentine leukocidin in the development of acute severe S. aureus infections and have elucidated other virulence mechanisms, including novel modes of internalisation, varying post-invasion strategies (featuring both upregulation and downregulation of virulence factors) and phenotypic switching. Recent double-blind, randomised, phase III/IV clinical trials have demonstrated the efficacy of linezolid and telavancin in hospital-acquired pneumonia (HAP) and complicated skin and skin-structure infections (cSSSIs) caused by MRSA. Tigecycline was non-inferior to imipenem/cilastatin in non-ventilator-associated HAP but was inferior in ventilator-associated pneumonia and has shown a higher rate of death than comparators on meta-analysis. Ceftaroline was clinically and microbiologically non-inferior to vancomycin/aztreonam in the treatment of MRSA cSSSI. Key resistance issues include a rise in vancomycin minimum inhibitory concentrations in MRSA, reports of clonal isolates with linezolid resistance mediated by acquisition of the chloramphenicol/florfenicol resistance gene, and case reports of daptomycin resistance resulting in clinical failure. Novel antimicrobial targets must be identified with some regularity or we will face the risk of untreatable S. aureus infections.
耐甲氧西林金黄色葡萄球菌（MRSA）仍然是引起严重医疗相关和社区获得性感染的主要多重耐药细菌病原体之一。本文综述了最近阐明 MRSA 所采用的毒力策略的研究、用于治疗严重 MRSA 感染的药物的关键临床试验，以及关于 MRSA 中抗菌耐药性对治疗期间临床成功的影响的累积数据。最近的临床前数据支持 Panton-Valentine 白细胞毒素在急性严重金黄色葡萄球菌感染中的种特异性作用，并阐明了其他毒力机制，包括新型内化模式、不同的入侵后策略（包括上调和下调毒力因子）和表型转换。最近的双盲、随机、III/IV 期临床试验表明，利奈唑胺和替考拉宁在耐甲氧西林金黄色葡萄球菌引起的医院获得性肺炎（HAP）和复杂皮肤和皮肤结构感染（cSSSIs）中的疗效。替加环素在非呼吸机相关性 HAP 中与亚胺培南/西司他丁等效，但在呼吸机相关性肺炎中不如亚胺培南/西司他丁，meta 分析显示死亡率高于对照药物。头孢洛林在治疗耐甲氧西林金黄色葡萄球菌 cSSSI 方面与万古霉素/氨曲南具有临床和微生物学等效性。关键的耐药问题包括耐万古霉素金黄色葡萄球菌最小抑菌浓度的上升、报道的具有氯苯乙酮/氟苯尼考耐药基因获得的利奈唑胺耐药克隆分离株，以及导致临床失败的达托霉素耐药的病例报告。必须定期确定新的抗菌靶标，否则我们将面临无法治疗的金黄色葡萄球菌感染的风险。
