Pharmacokinetics/Pharmacodynamics and Therapeutic Drug Monitoring of Ceftazidime/Avibactam in Patients With Gram‐Negative Bacterial Infections

Objectives: This study aimed to characterize ceftazidime/avibactam trough concentrations ( C min ) in patients infected with resistant Gram‐negative bacteria. Additionally, we assessed the risk factor associated with clinical cure, including joint optimal pharmacokinetic/pharmacodynamic (PK/PD) target. Methods: We conducted a single‐center observational retrospective study involving patients receiving ceftazidime/avibactam therapy for Gram‐negative infections and undergoing therapeutic drug monitoring of ceftazidime and avibactam. Analysis was performed on the C min of ceftazidime and avibactam. The joint PK/PD target of ceftazidime/avibactam was considered as optimal when both the PK/PD targets of ceftazidime (100% f T > 4 × MIC) and avibactam (100% f T > C T ) were simultaneously achieved; quasi‐optimal if only one was achieved; and suboptimal if neither was achieved. Finally, logistic regression analysis was utilized to detect potential variables associated with clinical cure. Results: This study analyzed a total of 39 infected patients, with results showing that the C min of ceftazidime and avibactam was 24.1 ± 14.3 mg/L (coefficients of variation 59.5%), and 6.0 ± 4.4 mg/L (coefficients of variation 73.5%), respectively. Patients with renal insufficiency exhibited significantly higher C min of ceftazidime and avibactam compared to those with normal renal function ( p < 0.05). Similarly, C min were elevated in patients receiving continuous renal replacement therapy (CRRT) versus non‐CRRT recipients ( p < 0.05). No significant difference in C min of ceftazidime and avibactam was observed between elderly and nonelderly patients. Clinically cured patients accounted for 76.9% (30/39) of the total. For 23 infected patients with minimum inhibitory concentration results, optimal joint PK/PD target was observed in 16 patients (69.6%) and quasi‐optimal in 7 patients (30.4%). Independent predictors of clinical cure were found to be optimal joint PK/PD target and co‐administered with aztreonam. Conclusions: The findings indicated that the C min of ceftazidime and avibactam exhibit significant variability. With the current regimen of ceftazidime/avibactam, the majority of patients can achieve clinical cure and optimal PK/PD target.