Background Ceftazidime-avibactam (CAZ-AVI) is a key agent for MDR-GNB, but significant pharmacokinetic (PK) variability in critically ill patients poses challenges to achieving optimal dosing. Objectives To investigate the association and influencing factors between CAZ-AVI serum concentration and clinical efficacy in critically ill patients, and specifically to evaluate the influence of disease severity on this relationship, with the aim of identifying a therapeutic target for critically ill patients with different disease severity. Methods A retrospective study was conducted of 168 critically ill patients receiving ceftazidime/avibactam between 2021 and 2025. The relationship between plasma drug concentration, clinical efficacy and disease severity was evaluated. Results 168 patients were included. C min of CAZ and AVI was significantly higher in the effective group than in the ineffective group (CAZ: 39.68 mg/L vs. 26.11 mg/L, P 0.001; AVI: 8.29 mg/L vs. 4.92 mg/L, P = 0.003). Multivariate analysis identified that CAZ C min was an independent positive predictor (P 0.05) and SOFA score on TDM day as an independent negative predictor (P 0.05) of clinical efficacy. Stratification by SOFA score revealed that this exposure-response relationship was markedly modified by disease severity. In the subgroup with less severely ill patients (SOFA score6), the positive association between CAZ concentration and clinical efficacy was markedly strengthened (P 0.001), with ROC analysis identifying an optimal predictive CAZ threshold of 34.79 mg/L (AUC = 0.829). Regarding safety, the overall incidence of adverse drug reactions (ADRs) was 15.03%, primarily elevated transaminases, acute kidney injury, and hematological abnormalities. A concentration-dependent risk for ADRs was established, with a CAZ concentration of 54.84 mg/L identified as the optimal predictive cut-off. Conclusion This retrospective analysis provides evidence that optimizing CAZ-AVI plasma concentrations is crucial for improving outcomes in critically ill patients, and that this relationship is significantly modulated by disease severity, necessitating a severity-adapted therapeutic drug monitoring (TDM) strategy.
Qian et al. (Thu,) studied this question.