Association of Vancomycin AUC/MIC and Trough Concentration With Early Clinical Response in Enterococcus or Coagulase-Negative Staphylococcus Infection: A Prospective Study

Abstract

This study was condcuted to examine the association of area under the curve (AUC)/minimum inhibitory concentration (MIC) and trough concentration (C_trough) of vancomycin with treatment outcome and nephrotoxicity in infections caused by Enterococcus spp. and coagulase-negative Staphylococci (CoNS). Peak and trough concentrations were used to calculate AUC in 89 patients receiving vancomycin for infections with Enterococcus spp. (n = 65) or CoNS (n = 24). Correlations between C_trough, AUC/MIC, early clinical response (ECR), and nephrotoxicity were assessed and cutoff values were determined. Sixty-three (70.8%) patients showed improvement in ECR and 10 (11.2%) experienced nephrotoxicity. Enterococcus spp. infections displayed correlations between AUC/MIC and ECR for AUC_{0-24 h}/MIC (r² = 0.27, P ≤ .05) and AUC_{24-48 h}/MIC (r² = 0.28, P ≤ .05), but not for C_trough (r² = 0.21, P > .05). There were no correlations between C_trough (r² = 0.26, P > .05), AUC_{0-24 h}/MIC (r² = −0.12, P > .05), AUC_{24-48 h}/MIC (r² = 0.01, P > .05) and ECR for CoNS. In the CoNS group, a moderate correlation was found between ECR and C_trough at a cutoff value of 6.9 μg/mL. In addition, nephrotoxicity is also moderately associated with AUC_{0-24 h} and AUC_{24-48 h} at 505.7 and 667.1 μg•h/mL, respectively. A strong correlation between nephrotoxicity and C_trough was observed when the cutoff value was 18.9 μg/mL. AUC/MIC during the first 48 h was a determinant of vancomycin efficacy in Enterococcus infections but not for CoNS. C_trough was not correlated with clinical outcome. Nephrotoxicity could be predicted using C_trough and AUC for infections with both pathogens.