Population Pharmacokinetics-Based Evaluation of Ceftazidime-Avibactam Dosing Regimens in Critically and Non-Critically Ill Patients With Carbapenem-Resistant Klebsiella pneumoniae.

Abstract

Purpose: This study aimed to describe the population pharmacokinetics (PopPK) of ceftazidime-avibactam (CAZ-AVI) in adult patients, and to develop optimal dosing regimens for both non-critically ill and critically ill patients by combining different pharmacokinetic/pharmacodynamic (PK/PD) targets.

Patients and methods: A prospective, single-center study involving patients who were infected with CRKP and received CAZ-AVI therapy was conducted. Nonlinear mixed-effect modeling was used to develop a PopPK model. The optimal dosing regimen was assessed using Monte Carlo simulation.

Results: The PopPK analysis of CAZ-AVI included 91 steady-state concentrations from 45 adult patients. The data were modeled using a one-compartment model. The typical population values of CAZ and AVI clearances were 2.96 L/h and 3.09 L/h, and the volumes of distribution were 17.76 L and 18.25 L, respectively. Our study showed that creatinine clearance (CrCL) calculated using the Cockcroft-Gault equation significantly affected the pharmacokinetics of CAZ-AVI. The Monte Carlo simulation optimized the dosing regimen for both non-critically ill and critically ill patients with varying renal functions, providing detailed supplements to the instructions.

Conclusion: Our study established a PopPK model for CAZ-AVI and proposed a reference for dosing regimen adjustment based on the severity of the disease and renal functional status.