title: Determining vancomycin Etest MICs in patients with MRSA bloodstream infection does not support switching antimicrobials.
abstract: Elevated vancomycin minimum inhibitory concentrations (MIC) have been reported to adversely affect clinical outcome in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). We therefore examined the association between vancomycin MIC and outcome considering various potential confounders.
  
  
  
  Clinical data and bacterial isolates were prospectively collected from patients with MRSA BSI from 2006 to 2012 as part of the Invasive Staphylococcus aureus Infection Cohort (INSTINCT) study. Antimicrobial susceptibility was assessed by Etest, broth microdilution (BMD) and VITEK 2. Bacterial genotypes were determined by spa typing. Using univariate and Cox regression analyses, we investigated the impact of low (≤1.0 mg/L) and high (≥1.5 mg/L) vancomycin Etest MIC on clinical outcomes.
  
  
  
  Ninety-one MRSA BSI episodes were included, of which 79 (86.8%) were caused by spa types t003, t032 and t045. High vancomycin MICs were seen only if using Etest but not confirmed using standard reference BMD. When episodes were stratified into low and high vancomycin Etest MIC groups, 30-day overall mortality was 34.5% and 27.3%, respectively (P = 0.64, OR 0.71; 95% confidence interval [CI] 0.27-1.79). Variables significantly associated with all-cause mortality in the Cox model were age (P = 0.003), acute physiology score (P = 0.0006), and Charlson comorbidity index (P = 0.018).
  
  
  
  Vancomycin MICs may vary dependent on testing methodologies and local MRSA epidemiology. The patients' underlying disease and individual comorbidities rather than elevated vancomycin MICs determine adverse clinical outcomes in MRSA BSI. Routine Etest MIC testing of MRSA isolates is of limited value for treatment decisions.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, 50935 Cologne, Germany; Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; German Centre for Infection Research, Partner Site Bonn-Cologne, Germany.
authors.forename: Nina J
authors.initials: NJ
authors.lastname: Hos
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, 50935 Cologne, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jazmati
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, 50935 Cologne, Germany.
authors.forename: Danuta
authors.initials: D
authors.lastname: Stefanik
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hellmich
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, 50935 Cologne, Germany.
authors.forename: Halil
authors.initials: H
authors.lastname: AlSael
authors.affiliation: Division of Infectious Diseases, Department of Medicine II, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors.forename: Winfried V
authors.initials: WV
authors.lastname: Kern
authors.affiliation: Division of Infectious Diseases, Department of Medicine II, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors.forename: Siegbert
authors.initials: S
authors.lastname: Rieg
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, 50935 Cologne, Germany.
authors.forename: Hilmar
authors.initials: H
authors.lastname: Wisplinghoff
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, 50935 Cologne, Germany; German Centre for Infection Research, Partner Site Bonn-Cologne, Germany. Electronic address: harald.seifert@uni-koeln.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Seifert
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, 50935 Cologne, Germany; Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Achim J
authors.initials: AJ
authors.lastname: Kaasch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics; D015331:Cohort Studies; D015897:Comorbidity; D052978:Disk Diffusion Antimicrobial Tests / Q000379:methods*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D014640:Vancomycin
keywords: Bacteraemia; Comorbidity; Disease severity; INSTINCT; MRSA; Mortality; Sepsis; Spa typing