New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance

被引:223
作者
Gould, Ian M. [1 ]
David, Michael Z. [2 ,3 ,4 ]
Esposito, Silvano [5 ]
Garau, Javier [6 ]
Lina, Gerard [7 ]
Mazzei, Teresita [8 ]
Peters, Georg [9 ]
机构
[1] Aberdeen Royal Infirm, Dept Med Microbiol, Aberdeen AB25 2ZN, Scotland
[2] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[3] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA
[4] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA
[5] Seconda Univ Napoli, Sez Malattie Infett, Dipartimento Med Pubbl Clin & Preventiva, Naples, Italy
[6] Hosp Univ Mutua Terrassa, Dept Med, Barcelona, Spain
[7] Univ Lyon, INSERM, Hosp Civils Lyon, Ctr Natl Reference Staphylocoques, Lyon, France
[8] Univ Florence, Dept Preclin & Clin Pharmacol, Florence, Italy
[9] Inst Med Microbiol, Munster, Germany
基金
美国国家卫生研究院;
关键词
Drug resistance; Meticillin-resistant Staphylococcus aureus; Pneumonia; Staphylococcal skin infections; Virulence; PANTON-VALENTINE LEUKOCIDIN; EVALUATING CEFTAROLINE FOSAMIL; INFECTIOUS-DISEASES SOCIETY; METHICILLIN-RESISTANT; COMPLICATED SKIN; UNITED-STATES; DOUBLE-BLIND; INFLAMMATORY RESPONSE; NOSOCOMIAL PNEUMONIA; DAPTOMYCIN-RESISTANT;
D O I
10.1016/j.ijantimicag.2011.09.028
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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. (C) 2011 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.
引用
收藏
页码:96 / 104
页数:9
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