Assessment of vancomycin dosing regimens in Intensive Care Unit patients with impaired renal function

Despite the large utilization of vancomycin in methicillin resistant Staphylococcus aureus (MRSA) infections, there is limited information regarding the proper dosing regimen in intensive care unit patients with impaired renal function. The objective of this study was (i) to conduct a population pharmacokinetic analysis of vancomycin in a population of critically ill patients; (ii) to assess the pharmacokinetic-pharmacodynamic profile of various vancomycin dosing regimens in the same set of patients.
Data were collected from routine care of 17 patients who were administered vancomycin as a loading dose followed by continuous infusion. MonolixTM was used to derive a population model. Two sets of dosing regimens simulations were performed using the individual parameter estimates of the final covariate model. Concentration-time profiles were evaluated by the probability of achieving an AUC/MIC ≥ 400 and a CT and C24 values less than 28 mg/L.
We found that the best population pharmacokinetic model consisted of a two-compartment linear model with an exponential model for parameter variability and a combined model (comb2) for the residual variability. Vancomycin clearance showed a significant dependence on patient renal function. ClCr baseline ranged from 33.40 to 157.16 ml/min and changes varied from 5.75 to 106.51 ml/min. Final estimates were: Cl (L/h) = 0.024 × ClCr + 0.27; Vc = 59.20 L and Vp = 97.30 L. Simulation data showed that with a 15 mg/kg loading dose and a 25 mg/Kg maintenance dose, 70.6% of the patients achieved an AUC/MIC ratio ≥ 400 with a CT and C24 values less than 28 mg/L.