Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients

Aims: To identify the variables affecting vancomycin pharmacokinetics in medical ICU patients and to evaluate the potential efficacy of dosage schedules by PK/PD analysis. Design: A retrospective pharmacokinetic analysis of serum levels obtained in routine vancomycin monitoring was performed. Setting: A 12-bed general ICU of a university teaching hospital. Patients: Forty-six vancomycin-treated ICU patients fitting the following criteria: over 18 years old; more than three concentration data per patient; absence of renal replacement support, cardiac surgery and neoplastic disorders. Interventions: Clinical information was collected from the patients' medical records. Details of vancomycin therapy, dosage and blood sampling times were obtained from pharmacokinetic reports. Population analysis were made by the standard two-stage approach. Measurements and main results: Vancomycin clearance and distribution volume were estimated individually assuming a one-compartment pharmacokinetic model. PK/PD analysis was performed by Monte Carlo simulation. In the ICU patients, higher Vd (nearly twice the quoted value of 0.72 l/kg) and different vancomycin clearance-creatinine clearance relationship were found. Renal function, the APACHE score, age and serum albumin accounted for more than 65% of drug clearance variability. Vancomycin standard dosages led to a 33% risk of not achieving the recommended AUC(24h)/MIC breakpoint for Staphylococcus aureus. Conclusions: The population kinetics and PK/PD analyses based on Monte Carlo simulation procedures offer an excellent tool for selecting the therapeutic option with the highest probability of clinical success in ICU patients.