Study of Optimal Administration Method of Tazobactam / Piperacillin Using Monte Carllo Simulation

Abstract

Monte Carlo simulation method was used to examine optimal administration method of Tazobactam / Piperacillin（TAZ/PIPC）against Pseudomonas aeruginosa（P. aeruginosa）．The dose to obtain?50% Time above MIC（%T>MIC）by renal functions and target attainment rates（TA%）?80% ware calculated for 12 administration methods. Pharmacokinetic parameters were established according to population pharmacokinetic analyses in Japanese patients with pneumonia, whereas MIC was determined using the MIC90 from the antibiogram of P. aeruginosa isolated at the Yamaguchi University Hospital in a 5-year period starting in 2011. Our recommended criteria for optimum administration was TA ?80% with 50%T＞MIC, and prioritizing facility for the patient（low-dose, lower frequencies and shorter infusion time）．The results obtained in 2015 suggest a recommendation of 2.25g × 4doses/day for patients with creatinine clearance（CLcr）<20mL/min, 4.5g × 3doses/day for patients with CLcr 20-29 mL/min, 4.5g × 4doses/day in patients of CLcr 30-79 mL/min（1hour infusion），and 4.5g × 4doses/day in patients of CLcr?80mL/min（3hours infusion）. However, there was variation in MIC90 levels between periods：some cases have much higher MIC90 value, in which case the optimal dosage could not be recommended within the indicated dose.