Association between Vancomycin Pharmacokinetic Parameters and Clinical and Microbiological Efficacy in a Cohort of...

Vancomycin pharmacokinetic/pharmacodynamic (PK/PD) targets have not been validated in the neonatal population as no specifically designed studies are available. The main goal of this study was to analyze the therapeutic vancomycin regimen, the 24-h area under the curve (AUC₂₄), and the trough plasma concentration (C) obtained that achieved clinical and microbiological effectiveness in a cohort of neonates. This was an observational, prospective, single-center study covering a period of 2 years. Eligible patients were neonates and young infants who were undergoing treatment with intravenous vancomycin for ≥72 h with ≥1 C available. The primary outcome was the association of C and AUC₂₄ with clinical and microbiological efficacy at the beginning (early clinical evolution [ECE]) and the end (late clinical evolution [LCE]) of treatment with vancomycin. A total of 43 patients were included, 88.4% of whom were cured. In ECE, the cutoff points of the receiver operating characteristic (ROC) curve were 238 mg · h/L (sensitivity of 61% and specificity of 88%) for AUC₂₄ and 6.8 μg/mL (sensitivity of 61% and specificity of 92%) for C. In LCE, the C value was 11 μg/mL, with a sensitivity of 80% and a specificity of 92%. In this analysis, AUC₂₄ was not considered a good predictor. Logistic regression showed that a vancomycin C of ≤6.8 μg/mL was associated with an unfavorable ECE (P = 0.001), being 18 times more likely to progress poorly compared to those with higher levels. AUC₂₄ and C are good predictors of ECE in this population. Concentrations close to 7 μg/mL and an AUC₂₄ of around 240 mg · h/L 48 h after antibiotic initiation seem to be sufficient to achieve clinical cure in most cases.