title: New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance.
abstract: 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.
authors.affiliation: Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, UK. i.m.gould@abdn.ac.uk
authors.forename: Ian M
authors.initials: IM
authors.lastname: Gould
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: David
authors.forename: Silvano
authors.initials: S
authors.lastname: Esposito
authors.forename: Javier
authors.initials: J
authors.lastname: Garau
authors.forename: Gerard
authors.initials: G
authors.lastname: Lina
authors.forename: Teresita
authors.initials: T
authors.lastname: Mazzei
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D017327:Clinical Trials, Phase IV as Topic; D017714:Community-Acquired Infections / Q000453:epidemiology / Q000382:microbiology; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology; D005098:Exotoxins / Q000378:metabolism; D006801:Humans; D007956:Leukocidins / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification* / Q000472:pathogenicity; D016032:Randomized Controlled Trials as Topic; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D037521:Virulence Factors