Open Access
Population Pharmacokinetics and Pharmacodynamics of Meropenem in Critically Ill Pediatric Patients
Author(s) -
Jumpei Saito,
Kensuke Shoji,
Yusuke Oho,
Hiroki Kato,
Shotaro Matsumoto,
Satoshi Aoki,
Hidefumi Nakamura,
Takanori Ogawa,
Mayumi Hasegawa,
Akimasa Yamatani,
Isao Miyairi
Publication year - 2021
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01909-20
Subject(s) - meropenem , medicine , pharmacodynamics , pharmacokinetics , critically ill , dosing , pediatric intensive care unit , intensive care unit , population pharmacokinetics , intensive care medicine , regimen , intensive care , population , pharmacology , antibiotics , biology , microbiology and biotechnology , environmental health , antibiotic resistance
This study investigates the optimal meropenem (MEM) dosing regimen for critically ill pediatric patients, for which there is a lack of pharmacokinetic (PK) studies. We conducted a retrospective single-center PK and pharmacodynamic (PD) analysis of 34 pediatric intensive care unit patients who received MEM. Individual PK parameters were determined by a two-compartment analysis. The median (range) age and body weight were 1.4 (0.03 to 14.6) years and 8.9 (2.7 to 40.9) kg, respectively, and eight (23.5%) patients received continuous renal replacement therapy (CRRT), three of whom received extracorporeal membrane oxygenation. Renal function, the systemic inflammatory response syndrome (SIRS) score for the clearance (CL), and the use of CRRT for the central volume of distribution ( V c ) were identified as significant covariates. The mean CL, V c , and peripheral volume of distribution ( V p ) were 0.45 liters/kg/h, 0.49 liters/kg, and 0.34 liters/kg, respectively. The mean population CL of MEM increased by 35% in patients with SIRS and V c increased by 66% in patients on CRRT in the final model. Dosing simulations suggested that the standard dosing regimen provided insufficient PD exposures of a 100% free time above the MIC, and higher doses (40 to 80 mg/kg of body weight/dose every 8 h) with a prolonged 3-h infusion were required to ensure the appropriate PD exposures for patients with SIRS. Our PK model indicated that critically ill pediatric patients are at risk of subtherapeutic exposure under the standard dosing regimen of MEM. A larger, prospective investigation confirming the safety and efficacy of higher concentrations and prolonged infusion of MEM is necessary.