Drug design, development and therapy
Model-Informed Ceftazidime-Avibactam Dosing Stratified by Renal Function and Renal Replacement Therapy Status in Critically Ill Patients: A Prospective Population Pharmacokinetic and Monte Carlo Simulation Study
By Hu J, Wang CH, Wang XJ and 10 others.
Abstract
Introduction
Carbapenem-resistant organisms (CROs) threaten critically ill patients, requiring model-informed ceftazidime-avibactam (CAZ-AVI) dosing by renal function and renal replacement therapy (RRT) status.
Materials and methods
Thirty-three patients were prospectively enrolled at one center (18 RRT; 15 non-RRT). RRT settings were recorded. Samples were collected at 0, 1, 2, 4, 6, and 8 h after first-dose and steady-state infusions. Population pharmacokinetic modeling used NONMEM. Monte Carlo simulations evaluated joint probability of target attainment (PTA) for minimum inhibitory concentration (MIC)-directed therapy and pathogen-specific cumulative fraction of response (CFR) for empirical therapy using BRICS MIC distributions under two targets: (1) CAZ 100% fT > MIC and AVI 100% fT > 1 mg/L; and (2) CAZ 50% fT > 4MIC and AVI 50% fT > 1 mg/L. Robust model-informed regimens required joint PTA ≥90% under both targets for MIC-directed therapy and CFR ≥90% under both for empirical therapy; lower values were exploratory.