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A correlation between vancomycin (VAN) trough concentrations (VTC) and area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC/MIC) has not been established in children/adolescents with cystic fibrosis (CF). The primary objective of this study was to determine the correlation between measured VTCs and AUC/MIC using population-based pharmacokinetics.A retrospective cohort study of children/adolescents diagnosed with CF, 6 to <18 years of age, treated with VAN for methicillin-resistant Staphylococcus aureus infection was conducted. The relationship between final VTCs and calculated AUC/MIC was assessed using Pearson and Spearman correlations. All tests were 2-tailed with alpha set at 0.05.Thirty children/adolescents, 7 to 17 years of age (median age 15 year; interquartile range: 9–17 years), were included. The mean final VAN dose was 58.03 ± 18.58 mg/kg/d, and the median final VTC was 12.6 (11–13.6) mg/L. The mean AUC/MIC was 355.34 ± 138.46 (Le model) versus 426.79 ± 178.92 (Stockmann model; P = 0.089). No correlation existed between VTCs and AUC/MIC using either the model by Le (r = 0.140; P = 0.461) or Stockmann (r = 0.115; P = 0.564). Using the Stockmann model, VAN dose (mg/kg/dose) was found to have a strong positive correlation with AUC (r = 0.8874; P < 0.0001) and AUC/MIC (r = 0.7877; P < 0.0001).VTCs did not correlate with AUC or AUC/MIC. Further research is needed to determine which estimate of VAN treatment efficacy is most appropriate for children and adolescents with CF infected with methicillin-resistant Staphylococcus aureus.