Vancomycin dose optimisation comparing a pharmacokinetic/pharmacodynamic model versus the pharmacokinetic model

Objectives

To compare vancomycin dosage adjustment by evaluating trough concentrations (Ctrough) of vancomycin and its pharmacokinetic/pharmacodynamic (PK/PD) correlation (AUC/MIC ≥400).

Methods

A retrospective study of 52 adult haematological patients and 29 ICU patients was carried out. Dosage adjustment was performed in routine clinical practice with Ctrough​​ and then compared using a PK/PD model. The probability of achieving the PK/PD target associated with the success of antimicrobial therapy was evaluated. When the susceptibility of the organism responsible for infection is not known, Monte Carlo simulation calculates the cumulative fraction of response (CFR) from the distribution of MIC values. Values of CFR >90% represent an optimal achieved regimen against a population of microorganisms.

Results

According to dosage adjustment performed ​​with Ctrough, in haematological patients the dose of vancomycin was increased in 65.4% compared with an increase in 53.8% of patients with the PK/PD model. No dose adjustment was needed in 21.1% of patients using Ctrough compared with 7.7% with the PK/PD model and in 13.5% of patients using Ctrough determination and in 38.5% of patients with the PK/PD model the dose was reduced. For ICU patients the dosage adjustment made ​​with Ctrough resulted in an increased dose of vancomycin in 79.4% of patients compared with 41.4% with the PK/PD model. No dose adjustment was needed in 3.4% of patients using Ctrough in comparison with 13.8% with the PK/PD model, and the dose was reduced in 17.2% of patients using Ctrough determination and in 44.8% with the PK/PD model.

Conclusions

Data for bacterial susceptibility combined with measured data for antibiotic concentrations using a PK/PD model predict and improve the dosage adjustment for individual patients. A larger study with more complete datasets are needed for validation before it can be fully introduced into clinical practice.