Creatinine Clearance, Ceftazidime-Avibactam Exposure, and Clinical Outcomes in a Real-World TDM Cohort: A Retrospective Observational Study

Purpose

Ceftazidime-avibactam (CAZ-AVI) is a key option for carbapenem-resistant Enterobacterales (CRE) infections, but whether creatinine clearance (CrCL) independently predicts outcomes or reflects disease severity is unclear. We investigated CrCL, drug exposure, and outcomes in patients with severe Gram-negative infections receiving CAZ-AVI with therapeutic drug monitoring (TDM). Patients and methods: This retrospective study included 224 patients receiving CAZ-AVI TDM at a tertiary hospital in China (May 2024-May 2025). Three cohorts were defined: trough-concentration (n=224) for factors influencing trough concentrations; concentration-outcome (n=194) for concentration-outcome associations using LASSO; and stable-dose (n=165) for baseline CrCL and outcomes. CrCL was analysed using restricted cubic splines and five prespecified analysis CrCL strata. Multivariable adjustment, E-values, LASSO, and bootstrap-validated ROC were used to separate CrCL from disease severity.