AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis

Antimicrob Agents Chemother. 2017 May 24;61(6):e02486-16. doi: 10.1128/AAC.02486-16. Print 2017 Jun.

Abstract

The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.

Keywords: MRSA; Staphylococcus aureus; experimental endocarditis; pharmacodynamic target; vancomycin MIC.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Economics, Pharmaceutical
  • Endocarditis / drug therapy*
  • Endocarditis, Bacterial / drug therapy
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity*
  • Microbial Sensitivity Tests
  • Rabbits
  • Vancomycin / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Vancomycin