The Impact of Augmented Renal Function on Vancomycin Pharmacokinetics in Neuro-critically Ill Patients

Introduction:

Hospital-acquired infections are relatively common in hospitalized patients, especially those who are critically ill or with invasive devices. Vancomycin is an antibiotic that is widely used to treat methicillin-resistant staphylococcus-aureus; an organism that is usually could be the causative of the hospital-acquired infections especially among critically ill patients. As vancomycin is mainly eliminated from the body through the kidney, the renal function plays an important role in the dosing of vancomycin. Augmented renal function is a common condition among neurocritical ill patients. The aim of this study is to observe the pharmacokinetics and optimize the dosing of vancomycin in neurocritical ill patients.

Methods:

A prospective observational study of neurocritical ill patients received vancomycin at University of Alberta Hospital. Population pharmacokinetics of vancomycin were conducted using Monolix software. Moreover, non-compartmental analysis was conducted to observe the vancomycin pharmacokinetics differences among patients. Monte Carlo simulations were performed to predict the percentage of patients reaching the target concentrations following different doses.

Results:

A total of 55 patients with 149 observations were included in this study. The population clearance was 0.083 L/kg.hr, and the volume of distribution was 1.02 L/kg. The model which best fitted the population was one compartment model with creatinine clearance (CrCl) and body mass index added as covariates on vancomycin clearance. In the non-compartmental analysis, there were 7 out of 11 patients with augmented renal function. There was a positive correlation between the vancomycin clearance and CrCl (r² = 0.3346, P=0.04), and a negative correlation between area under the curve-to-dose ratio and CrCl (r² = 0.5778, P=0.003).

Conclusion:

Vancomycin clearance is affected by changes in CrCl observed in patients with augmented renal function. Therefore, dosing optimization in such population is essential to reach the target concentrations.