Objective To preliminarily evaluate the clinical efficacy of polymyxin combination treatment in patients with ceftazidime/avibactam(CZA)-resistant (inhibition zone diameter of CZA measured by disc diffusion method was ≤22 mm) carbapenem-resistant Gram-negative bacteria (CR-GNB) infection. Methods Hospitalized patients who received polymyxin combination for the treatment of CZA-resistant CR-GNB infection in a hospital from June 2021 to May 2023 were included in the study. According to the antimicrobial susceptibility results of CZA by disc diffusion method, patients were divided into CZA inhibition zone diameter 20-22 mm group and CZA inhibition zone dia- meter < 20 mm group. Clinical efficacy and safety of anti-infection treatment in the two groups of patients were observed. Results A total of 75 patients were enrolled, including 41 patients with CZA inhibition zone diameter 20-22 mm and 34 patients with CZA inhibition zone diameter < 20 mm. The general data between the two groups of patients were not statistically different (all P>0.05). The proportion of the types, dosage and combination regimens of polymyxins between the two groups of patients were not statistically different (all P>0.05). The number of bacterial strains and the diameter of CZA inhibition zone of different types of CR-GNB isolates between the two groups were all statistically different (all P < 0.05). Clinical effective rate, microbiological clearance rate, 28-day mortality, and discharge mortality between the two groups of patients were not statistically different (all P >0.05). Changes in renal safety indexes between the two groups of patients before and after treatment with polymyxins were not statistically different (all P>0.05). Conclusion Clinical and microbiological efficacy of combination treatment with polymyxins for CZA-resistant CR-GNB infected patients is approximately 50%. The efficacy of polymyxin combination in the treatment of infection caused by strains with inhibitory zone diameter < 20 mm is consistent with those with diameter of 20-22 mm, but further validation with a larger size of clinical specimens is needed.