Background: Multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a major public health threat. Ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) are active against many MDR P. aeruginosa, and can improve the management of infected patients. However, resistance to the new antimicrobials has emerged in many countries. In this study we aimed to test the susceptibility of clinical isolates of MDR P. aeruginosa in our hospital to CZA and C/T, and to identify the role of carbapenemases in antimicrobial resistance. Methods: We studied 51 MDR P. aeruginosa isolates from 51 ICU patients admitted at Benha University Hospital in Egypt. Identification was done by VITEK-2 (BioMerieux). Testing the antimicrobial susceptibility was performed by disk diffusion method according to CLSI 2022. For all isolates, we used Carba Blue Test for phenotypic identification of carbapenemases, and multiplex PCR for detection of carbapenemase genes. Results: The isolates were 98% resistant to meropenem, while 23.5% were susceptible to each of C/T and CZA. Carbapenemase production was common, mostly by metallo- beta- lactamases (MBL). The most common carbapenemase genes were NDM, VIM and SIM. Carba Blue test identified carbapenemases in 52.9%, while multiplex PCR identified carbapenemase genes in 91.1%. Conclusion: Compared to conventional antibiotics, both CZA and C/T have shown moderate efficacy against our MDR P. aeruginosa isolates, making them good choices for the treatment of infection by some MDR P. aeruginosa. PCR is more sensitive than Carba Blue in detection of carbapenemase production.