Initial dosage regimen of vancomycin for septic shock patients: a pharmacokinetic study and Monte Carlo simulation

To evaluate the pharmacokinetic parameters of vancomycin in septic shock patients and to determine the vancomycin dosage to achieve requisite pharmacokinetic/pharmacodynamic (PK/PD) target against methicillin resistant Staphylocccus aureus (MRSA) in patients with septic shock.

Pharmacokinetic parameters of vancomycin in 12 septic shock patients were assessed. Then, the Monte Carlo simulation was performed to calculate the probabilities of target attainment (PTAs) to reach target AUC0-24/MIC of 400 and 450 mg.h/L.

The total clearance (CL) and the volume of the central compartment (Vc) of vancomycin was 3.34±1.39 L/h and 0.14±1.43 L/kg, respectively. For Staphylococcalspp. with low MICs of 0.125 and 0.5 mg/L, the administration of vancomycin 30 mg/kg as the loading dose, followed by the maintenance dose of 20 mg/kg every six, eight, 12, and 24 hours achieved >90% PTAs to reach target AUC0-24/MlC: For pathogens with MIC of 1, and 1.5 mg/L, the vancomycin maintenance dose of 20 mg/kg every six, eight, and 12 hours and every six and eight hours respectively to achieve >90% PTA.

High dose ofvancomycin is required to achieve PK/PD target for treatment of MRSA septic shock, especially if MRSA MIC is higher than 1 mg/L.