New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis,
treatment and resistance.
Author(s): Gould IM, David MZ, Esposito S, Garau J, Lina G, Mazzei T, Peters G.
Affiliation(s): Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill,
Aberdeen AB25 2ZN, UK. i.m.gould@abdn.ac.uk
Publication date & source: 2012, Int J Antimicrob Agents. , 39(2):96-104
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.
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