Infection and Drug Resistance (Feb 2024)
Model-Informed Precision Dosing of Imipenem in an Obese Adolescent Patient with Augmented Renal Clearance and History of Schizophrenia
Abstract
Yueliang Chen,1,* Yun Han,2,3,* Feng Guo,1 Zhenwei Yu2,3 1Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Research Center for Clinical Pharmacy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Guo; Zhenwei Yu, Email [email protected]; [email protected]: Imipenem is a broad-spectrum antibiotic that has been used in treating severe infections and exhibits a time-dependent PK/PD profile. Its dose should be adjusted based on renal function. However, there is little experience with imipenem dosing in obese adolescent patients with augmented renal clearance (ARC) and history of schizophrenia. This case reported successful dosing of imipenem in an obese adolescent patient with ARC based on therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD). A 15-year-old male adolescent patient with history of schizophrenia was diagnosed with ventilator-associated pneumonia due to carbapenem-susceptible Klebsiella pneumoniae and received imipenem treatment (0.5 g every 8 hours with a 1-hour infusion). However, the exposure of imipenem was suboptimal due to ARC, and there is no available model for MIPD in this patient. Thus, we utilized prediction error to find a population pharmacokinetic model that fit this patient and ran Maximum a posteriori Bayesian estimation and Monte Carlo simulation based on screened models to predict changes in drug concentrations. The dose of imipenem was adjusted to 0.5 g every 6 hours with a 2-hour infusion, and subsequent TDM revealed that dosing adjustment was accurate and successful. Finally, the patient’s status of infection improved. This study will be beneficial to imipenem dosing in similar cases in the future, thereby improving the safety and effectiveness of imipenem or other antibiotics.Keywords: case report, imipenem, therapeutic drug monitoring, population pharmacokinetic
