LAUSR

The objective of this pharmacokinetic (PK)/pharmacodynamic (PD) analysis was to evaluate the efficacy of different dosing regimens of ceftazidime-avibactam (CZA) for the treatment of extensively drug-resistance (XDR) Pseudomonas aeruginosa pulmonary infections by using optimized two-step-administration therapy (OTAT) and traditional infusion (TI). We used Monte Carlo simulations (MCS) to integrate PK parameters with PD parameters to assess the adequacy of ceftazidime-avibactam dosing for critically ill patients with XDR P. aeruginosa pulmonary infections. Dosing models were as follows: 2.5 g q8h, 2.5 g q6h, 4 g q8h, 4g q6h, 1.25 g q8h, 1.25 g q6h, and 0.94 g q12h. MCS showed that the cumulative fraction of response (CFR) of all dosing regimens of OTAT was higher than 90%. The probability of target attainments (PTAs) of all dosing regimens of OTAT at MICs of 16-32 mg/L was higher than those of TI. Based on the models, PK/PD goals were met with OTAT regimens even with high MICs (>16 mg/L) compared with traditional infusion intervals. Our work indicated that OTAT with sufficient pharmacokinetic exposures could improve the efficacy of CZA for critically ill patients with XDR P. aeruginosa pulmonary infections.