title: Optimizing the detection of methicillin-resistant Staphylococcus aureus with elevated vancomycin minimum inhibitory concentrations within the susceptible range.
abstract: BACKGROUND
  Determination of vancomycin minimum inhibitory concentration (MIC) can influence the agent used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We studied diagnostic accuracy using E-test and VITEK(®) 2 against a gold standard broth microdilution (BMD) methodology, the correlation between methods, and associations between vancomycin MIC and MRSA phenotype from clinical isolates.
  
  
  METHODS
  MRSA isolates were obtained from April 2012 to December 2013. Vancomycin MIC values were determined prospectively on all isolates by gradient diffusion E-test and automated VITEK(®) 2. The Clinical and Laboratory Standards Institute reference BMD method was performed retrospectively on thawed frozen isolates. Diagnostic accuracy for detecting less susceptible strains was calculated at each MIC cutoff point for E-Test and VITEK(®) 2 using BMD ≥1 µg/mL as a standard. The correlation between methods was assessed using Spearman's rho (ρ). The association between MRSA phenotype and MIC for the three methods was assessed using Fisher's exact test.
  
  
  RESULTS
  Of 148 MRSA isolates, all except one (E-test =3 µg/mL) were susceptible to vancomycin (MIC of ≤2 µg/mL) irrespective of methodology. MICs were ≥1.0 µg/mL for 9.5% of BMD, 50.0% for VITEK(®) 2, and 27.7% for E-test. Spearman's ρ showed weak correlations between methods: 0.29 E-test vs VITEK(®) 2 (P=0.003), 0.27 E-test vs BMD (P=0.001), and 0.31 VITEK(®) 2 vs BMD (P=0.002). The optimal cutoff points for detecting BMD-defined less susceptible strains were ≥1.0 µg/mL for E-test and VITEK(®) 2. E-test sensitivity at this cutoff point was 0.85 and specificity 0.29, while VITEK(®) 2 sensitivity and specificity were 0.62 and 0.51, respectively. Multiresistant MRSA strains tended to have higher MIC values compared to nonmultiresistant MRSA or epidemic MRSA 15 phenotypes by E-test (Fisher's exact P<0.001) and VITEK(®) 2 (Fisher's exact P<0.001).
  
  
  CONCLUSIONS
  Overall diagnostic accuracy and correlations between MIC methods used in routine diagnostic laboratories and the gold standard BMD showed limited overall agreement. This study helps optimize guidance on the effective use of vancomycin.
authors.affiliation: SA Pharmacy, Flinders Medical Centre, Bedford Park, SA, Australia; Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, SA, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Phillips
authors.affiliation: SA Pathology, Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, SA, Australia.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Wells
authors.affiliation: SA Pathology, Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, SA, Australia.
authors.forename: Marianne
authors.initials: M
authors.lastname: Martinello
authors.affiliation: SA Pathology, Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, SA, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Smith
authors.affiliation: Flinders Centre for Epidemiology and Biostatistics, School of Medicine, Flinders University, Adelaide, SA, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Woodman
authors.affiliation: Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, SA, Australia; SA Pathology, Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, SA, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Gordon
keywords: MIC; MRSA; sensitivity; specificity; susceptibility; vancomycin