Background Carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections have been widely spreading in our country in recent years, posing a great challenge to clinical work. Colistin sulfate and ceftazidime-avibactam are the last resort for treating CRE and CRPA. Objective To compare the effect of colistin sulfate and ceftazidime-avibactam for treating CRE and CRPA infections.Methods Basic information of patients with CRE or CRPA infections treated with colistin sulfate or ceftazidime-avibactam and outcomes after anti-infective treatment were collected, respectively.Results A total of 82 patients were included in this study, with 42 cases in the colistin sulfate group and 40 cases in the ceftazidime-avibactam group. The median age in the colistin sulfate group was 83.0 (62.8-91.0) years, and 31 cases were male. In the ceftazidime-avibactam group, the median age was 80.5 (56.5-91.8) years, and there were 29 males. There was no statistical difference in the basic information between the colistin sulfate group and the ceftazidime-avibactam group. Regarding outcomes, compared with the ceftazidime-avibactam group, the clinical cure rate and 7-day survival rate in the colistin sulfate group were 50% vs 40%, and 71.4% vs 62.5%, without significant difference (P＞0.05, respectively). Concerning adverse effects, no statistically significant difference was observed in the incidence of renal injury between the two groups. Conclusion The effectiveness of colistin sulfate in treating CRE or CRPA infections is similar to ceftazidime-avibactam, with no significant differences. In clinical practice, specific drugs can be selected for anti-infective treatment based on drug availability.