ObjectiveTo evaluate the efficacy of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections (BSIs) or lower respiratory tract infections (LRTIs) – caused by extensive drug-resistant or pan drug-resistant (XDR/PDR)Pseudomonas aeruginosa.MethodThe two-fold dilution method was used to determine the minimum inhibitory concentrations (MICs) of CZA/AZA against XDR/PDRP. aeruginosa. Whole-genome sequencing was used to analyze the resistance determinants of each isolate. Monte Carlo simulations (MCSs) were used to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of each CZA/AZA dosing regimenviatraditional infusion (TI)/optimized two-step-administration therapy (OTAT).ResultsWe found that XDR/PDR P. aeruginosa may carry some rare MBLs (e.g.: IND-6, SLB-1, THIN-B).P. aeruginosaisolates producing IMP-45, VIM-1, or VIM-2 were inhibited by AZA at a concentration of 2 to 8 mg/L. All isolates producing IND-6 plus other serine β-lactamases were high-level resistant to CZA/AZA (MICs >64 mg/L). All simulated dosing regimens of CZA/AZA against BSIs-causing XDR/PDRP. aeruginosaachieved 100% PTA when the MIC was ≤32 mg/L.ConclusionAZA has been considered as an option for the treatment of infections caused by XDR/PDRP. aeruginosaproducing IMP-45, VIM-1, or VIM-2. OTAT with sufficient pharmacodynamic exposure may be an optimal treatment option for XDR/PDRP. aeruginosawith a high-level MIC of CZA/AZA.