title: Management of serious meticillin-resistant Staphylococcus aureus infections: what are the limits?
abstract: Severe (life-threatening) meticillin-resistant Staphylococcus aureus (MRSA) infection continues to be treated with vancomycin despite accumulating evidence of poor outcome, increasing resistance and unachievable pharmacokinetic/pharmacodynamic (PK/PD) targets. The minimum inhibitory concentration (MIC) susceptibility breakpoint for vancomycin was recently reduced to 2 mg/L. Whilst the great majority of clinical isolates are thus still classified as susceptible, the available clinical evidence argues for a method-dependent breakpoint of 0.5 mg/L (broth dilution) or 1.0 mg/L (Etest), which would classify many strains as resistant, or at best intermediate. However, automated susceptibility testing systems are not currently capable of performing accurately at this low level, and such low breakpoints are unsatisfactory because the poor reproducibility of tests (plus or minus one doubling dilution) results in a critical non-reproducibility around the modal MIC of 1 mg/L described in most published data. Therefore, vancomycin should be used with caution in severe (life-threatening) staphylococcal disease and the MIC should always be reported by method. Daptomycin is generally preferred for bacteraemia/endocarditis and linezolid for pneumonia. Better outcome data for vancomycin, based on achievable PK/PD targets and using robust MIC tests, are urgently required.
authors.affiliation: Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB252ZN, UK. i.m.gould@abdn.ac.uk
authors.forename: Ian M
authors.initials: IM
authors.lastname: Gould
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.forename: Silvano
authors.initials: S
authors.lastname: Esposito
authors.forename: Francesco
authors.initials: F
authors.lastname: Gudiol
authors.forename: Teresita
authors.initials: T
authors.lastname: Mazzei
authors.forename: Javier
authors.initials: J
authors.lastname: Garau
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy; D017576:Daptomycin / Q000627:therapeutic use; D004697:Endocarditis, Bacterial / Q000188:drug therapy; D006801:Humans; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000627:therapeutic use; D023303:Oxazolidinones / Q000627:therapeutic use; D018410:Pneumonia, Bacterial / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D017334:Teicoplanin / Q000627:therapeutic use; D000078304:Tigecycline; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D017334:Teicoplanin; D014640:Vancomycin; D000078304:Tigecycline; D008911:Minocycline; D000069349:Linezolid; D017576:Daptomycin