Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulation

AIM

To estimate the vancomycin pharmacokinetic profile in adult ICU patients and to assess vancomycin dosages for increasing the likelihood of optimal exposure.

METHODS

Five hundred and sixty-nine concentration–time data from 191 patients were analysed using a population pharmacokinetic approach (NONMEN™). External model evaluation was made in 46 additional patients. The 24 h area under the concentration–time curve (AUC(0,24 h)) was derived from the final model. Minimum inhibitory concentration (MIC) values for S. aureus were obtained from the EUCAST database. AUC(0,24 h) : MIC ≥ 400 was considered as PK/PD efficacy index. The probability of different dosages attaining the target considering different strains of S. aureus and patient subgroups was estimated with Monte Carlo simulation.

RESULTS

Vancomycin CL showed a significant dependence on patient age and renal function whereas Cr_Se > 1 mg dl⁻¹ increased V more than twofold. For our representative ICU patient, 61 years, 73 kg, Cr_Se= 1.4 mg dl⁻¹, measured CL_Cr= 74.7 ml min⁻¹, the estimated values were CL = 1.06 ml min⁻¹ kg⁻¹ and V= 2.04 l kg⁻¹. The cumulative fraction of response for a standard vancomycin dose (2 g day⁻¹) was less than 25% for VISA strains, and 33% to 95% for susceptible S. aureus, depending on patient characteristics.

CONCLUSIONS

Simulations provide useful information regarding the initial assessment of vancomycin dosing, the conventional dosing regimen probably being suboptimal in adult ICU patients. A graphic approach provides the recommended dose for any selected probability of attaining the PK/PD efficacy target or to evaluate the cumulative fraction of response for any dosing regimen in this population.