title: Does resistance in severe infections caused by methicillin-resistant Staphylococcus aureus give you the 'creeps'?
abstract: OBJECTIVE
  The clinical implications of reduced vancomycin susceptibility amongst methicillin-resistant Staphylococcus aureus (MRSA) are controversial, and crossresistance to daptomycin amongst such strains has been reported. As a consequence of 'MIC creep', higher trough levels were recommended for serious infections. This review focusses on the new data published in the past 18 months that pertain to these issues.
  
  
  RESULTS
  Heteroresistant vancomycin-intermediate Staphylococcus aureus reduces the clinical response rates to vancomycin in bacteraemic MRSA patients without impacting on mortality as opposed to 'MIC creep' with vancomycin minimum inhibitory concentration (MIC) levels of ≥1.5 mg/l that are significantly associated with mortality. Although daptomycin resistance is rare, 'concomitant MIC creep' amongst MRSA isolates with increasing vancomycin MICs may occur or exist concurrently amongst such strains. The aggressive vancomycin dosing regimens are still associated with unacceptable high microbiological failure rates and it is not currently possible to achieve probability of target attainment at higher vancomycin MICs of 2 mg/l. The nephrotoxic impact of high-dose vancomycin therapy has been confirmed.
  
  
  CONCLUSIONS
  Continued monitoring of patients on aggressive vancomycin dosing schedules is advised. Unless alternative dosing strategies prove otherwise efficacious, an alternative antibiotic should be considered for severe MRSA infections with vancomycin MICs greater than 1 mg/l. The utility of vancomycin may be waning but will depend on the prevalence of resistant MRSA phenotypes in a specific ICU.
authors.affiliation: Department of Clinical Microbiology, Ampath National Laboratory Services, Milpark Hospital, Parktown, Johannesburg, South Africa.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Brink
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017576:Daptomycin; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006023:Glycoproteins; D006801:Humans; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000627:therapeutic use; D012720:Severity of Illness Index; D013203:Staphylococcal Infections / Q000188:drug therapy*; D020713:Vancomycin Resistance / Q000187:drug effects*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D006023:Glycoproteins; D023303:Oxazolidinones; D000069349:Linezolid; D017576:Daptomycin