• Tatsuro Tamatsukuri, Masayuki Ohbayashi, Noriko Kohyama, Yasuna Kobayashi, Toshinori Yamamoto, Kenichiro Fukuda, Shunsuke Nakamura, Yasufumi Miyake, Kenji Dohi, and Mari Kogo.
• Division of Pharmacotherapeutics, Department of Clinical Pharmacy, Showa University School of Pharmacy, Tokyo, Japan. Electronic address: t.tamatsukuri@gmail.com.
• J. Infect. Chemother. 2018 Oct 1; 24 (10): 834-840.

AbstractIn recent years, augmented renal clearance (ARC), in which renal function is excessively enhanced, has been reported, and its influence on β-lactam antibiotics has been investigated. In this study, we aimed to determine the optimum population pharmacokinetic model of meropenem in patients with sepsis with ARC, and evaluated dosing regimens based on renal function. Seventeen subjects (6 with ARC and 11 without) were enrolled in this study. Predicted meropenem concentrations were evaluated for bias and precision using the Bland-Altman method. To examine the dosing regimen, Monte Carlo simulation was performed to calculate the cumulative fraction of response (CFR). In patients with ARC, the bias (average of the predicted value and measured value residuals) of models constructed by Crandon et al. (2011), Roberts et al. (2009), and Jaruratanasirikul et al. (2015) were 5.96 μg/mL, 10.91 μg/mL, and 4.41 μg/mL, respectively. Following 2 g meropenem every 8 h (180 min infusion), CFR ≥ 90%, a criterion of success for empirical therapy, was achieved, even with creatinine clearance of 130-250 mL/min. For patients with sepsis and ARC, the model of Jaruratanasirikul et al. showed the highest degree of accuracy and precision and confirmed the efficacy of the meropenem dosing regimen in this patient population.Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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