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.

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% Results: We analyzed 211 blood samples (120 RRT; 91 non-RRT). Creatinine clearance (CrCL) was retained in the final non-RRT models, whereas no covariate was retained in the final RRT models. RRT-model clearance (CL)/volume of distribution (V Conclusion: Our study describes the pharmacokinetics of CAZ-AVI in critically ill patients and provides model-informed dosing regimens stratified by renal function and RRT status for both empirical and targeted therapy. Larger, multicenter prospective studies are warranted to validate these findings.