Objective To evaluate the efficacy and safety of ceftazidime avibactam compared with polymyxin based combination therapy in patients with carbapenem resistant Pseudomonas aeruginosa infection. Methods Retrospective analysis was carried out on the patients infected with carbapenem resistant Pseudomonas aeruginosa in the ICU of the First Affiliated Hospital of Nanjing Medical University from June 2019 to January 2022. They were divided into ceftazidime avibactam group and polymyxin B group. The clinical data of patients were collected, including basic information such as gender, age, diagnosis, and length of stay. The comparative efficacy indicators included bacterial clearance rate, 28-day mortality rate and the incidence of adverse reactions such as liver and kidney dysfunction. Results A total of 55 patients were included, including 25 patients in the ceftazidime avibactam group and 30 patients in the polymyxin B group. There was no statistically significant difference in basic indicators, bacterial clearance, 28-day mortality, and adverse reactions between the two groups. The length of hospital stay in the ceftazidime avibactam group was longer than that in the polymyxin B group (49 (34, 78) vs 26 (15.75, 40.5), P=0.001<0.05), and ceftazidime avibactam group has fewer antibiotic combinations than polymyxin B group. Conclusion Compared with polymyxin B, ceftazidime averbactam has similar effects in clinical cure and bacterial clearance, and there is no statistical difference in adverse reactions. It increases the choice of clinical drugs and helps to reduce the pressure on public health.