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%fT > 4 × MIC) and avibactam (100%fT > 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.