Vancomycin Dosing Regimen to Obtain the Target Area Under the Concentration-Time Curve, Which Provides an Early...

Objectives: This study aimed to clarify the area under the curve (AUC) for obtaining better clinical outcomes and to demonstrate vancomycin dosing for achieving the AUC in haemodialysis (HD). Methods: The vancomycin concentration was measured before the second HD. The AUC_24-48h after the initial HD was assessed to evaluate its correlation with an early clinical response and to determine the dosing regimen, assuming an inter-dialysis interval of 48 h, even if the interval was 72 h. Results: An AUC/MIC ≥ 400 was an independent factor for an early response in treating MRSA infections and infections caused by methicillin-resistant Gram-positive organisms. An AUC of 600-700 μg·h/mL did not increase the incidence of adverse effects compared with that of <600 μg·h/mL. An AUC of 400-700 μg·h/mL was obtained in 90.5% of patients with a loading dose of 30 mg/kg followed by a maintenance dose of 10 mg/kg. Pre-dialysis concentrations were significantly higher than the trough concentration required in non-HD patients to achieve the same AUC category, and AUC_24-48h was strongly correlated with pre-dialysis concentrations (R² = 0.921). In a receiver operating characteristic curve, the cut-off value for an early response was 16.8 μg/mL for the pre-dialysis concentration/MIC. Conclusions: AUC_24-48h after the initial HD/MIC of ≥400 μg/mL improves the clinical outcomes in patients on HD, and the target PK/PD can be achieved with an upper range of the recommended dose. The pre-dialysis concentration may be a reliable surrogate for the AUC, and the vancomycin dose could be adjusted according to this PK target.