Importance of vancomycin loading doses in intermittent infusion regimens

Purpose

Delayed achievement of target vancomycin serum concentrations may adversely affect clinical outcomes. The objective of this retrospective study was to explore the real frequency of loading dose use and to evaluate the impact of loading dose for the achievement of vancomycin PK/PD target in adult patients treated with intermittent vancomycin. As a secondary aim we determined optimal vancomycin loading dose based on individual pharmacokinetic calculations.

Methods

Vancomycin pharmacokinetic models were computed using two-compartmental analysis. Based on these models AUC₂₄ were calculated. Unpaired t-test was used to compare AUC₂₄ achieved in patients treated with and without vancomycin loading dose.

Results

Vancomycin loading dose was administered only in 17.8% patients. Volume of distribution and clearance median values (interquartile range) for vancomycin in whole study population (n = 45) were 0.69 (0.55–0.87) L/kg and 0.0304 (0.0217–0.0501) L/h/kg, respectively. The AUC₂₄ was significantly higher in patients taking loading dose compared with the group without loading dose: mean (SD) AUC₂₄ was 496 (101) vs. 341 (77) mg h/L. Proportion of patients reaching PK/PD goal was 87.5% and 24.3% with and without loading dose administration, respectively. Considering individual pharmacokinetic parameters optimal vancomycin loading dose was 27.5 mg/kg of body weight.

Conclusions

Loading dose administration plays crucial part in rapid attainment of vancomycin PK/PD target in adult patient treated with intermittent vancomycin, although it is not frequently used in clinical practise. The optimal loading dose of 25–30 mg/kg of body weight should be routinely administered to adult patients treated with intermittent vancomycin.