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

OBJECTIVE: 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.

MATERIAL AND METHOD: 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.

RESULTS: 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.

CONCLUSION: 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.