Initial vancomycin dosing protocol to achieve therapeutic serum concentrations in patients undergoing hemodialysis.

Abstract

Although recent consensus guidelines proposed more aggressive vancomycin troughs of >10 or 15-20 mg/L for complicated Staphylococcus aureus infections, dosing information to achieve these targets in patients undergoing hemodialysis (HD) is scarce. We used Monte Carlo simulation (MCS) methods with a previously published population-pharmacokinetic model and relevant patient demographics to evaluate and revise our existing vancomycin dosing protocol (1000-mg load followed by 500-mg maintenance dose, with doses infused during the last hour of dialysis). A new protocol (1000-mg load followed by 500-mg maintenance dose for patients <70 kg, 1250-mg followed by 750-mg for those 70-100 kg, and 1500-mg followed by 1000-mg for those >100 kg) was developed and prospectively validated to achieve therapeutic serum troughs in patients undergoing high-flux HD. MCSs predicted that our existing protocol would be suboptimal in more than one-third of patients. Simulations predicted that the new vancomycin dosing protocol would achieve maintenance (pre-HD) troughs of 10-20 mg/L in 86.0% of cases including 15-20 mg/L in 35.2%. In prospective validation, the observed postload trough (pre-HD session 2) was 13.5 ± 3.4 mg/L with 76.9% of levels (20 of 26) between 10 and 20 mg/L. The observed maintenance trough was 17.3 ± 4.0 mg/L with 65.5% (19 of 29) between 10 and 20 mg/L and 89.7% (26 of 29) within 10% of the upper limit (ie, 10-22 mg/L). In this study, a practical vancomycin dosing protocol for patients undergoing HD was developed and prospectively validated to achieve therapeutic serum concentrations in the clinical setting.