Abstract: OBJECTIVE To observe the clinical effiacy of cefoperazone/sulbactam and meropenem in the treatment of pneumonia caused by extended spectrum β-lactamase producing Escherichia coli(ESBLs-E.coli) and ratational treatment reduces the incidence of ESBLs-E.coli and carbapenem resistant E.coli(CR-E.coli). METHODS From June 2019 to June 2021, a total of 419 patients with moderate pulmonary infection by ESBLs-E.coli were selected in the department of respiratory medicine, Shanghai Neuromedical Center, and they were divided into three groups according to visiting sequence and antibiotic application based on conventional treatment: the sulperazon group with 104 cases received cefoperazone/sulbactam continuously treated for 14 d, the meropenem group with 127 cases received meropenem continuously treated for 14 d, and the rotation group with 188 cases first received cefoperazone/sulbactam treated for 7 d, and then received meropenem for 7 d. The three groups of patients had the same treatment plan except for the different use of antibacterial drugs. After 14 d, the clinical efficacy of the three groups of patients was observed, and the alveolar lavage fluid of all patients who were not cured after treatment was collected for bacterial culture identification and drug sensitivity analysis for three consecutive days. The number of patients with ESBLs-E.coli and CR-E-coli cultured from the alveolar lavage fluid after treatment was statistically analyzed. RESULTS There was no significant difference in treatment efficacy between every two groups in three groups. Compared with after treatment, the E.coli resistance rate in rotation group of cephalosporin III(cefotaxime, ceftriaxone) and carbapenems(imipenem, meropenem and ertapenem) were significantly different from that in sulperazon group and meropenem group(the drug resistance rate of rotation group were significantly lower than other 2 groups, P<0.05). After treatment, ESBLs-E.coli was detected in alveolar lavage fluid of patients in 63, 66 and 53 cases in the sulpersen group, meropenem group and rotation group who were not cured. There was significant difference between rotation and sulperazon or meropenem(the rotation was significantly lower than sulperazon or meropenem group, P<0.05), and there was no significant difference between sulperazon and meropenem group; CR-E.coli was 7, 8, 2 cases in alveolar lavage fluid of sulperazon, meropenem and rotation group after treatment, respectively; there was significant difference between rotation and sulperazon or meropenem group(the rotation was significantly lower than sulperazon or meropenem group, P<0.05); there was no significant difference between sulperazon and meropenem. CONCLUSION There is no significant difference in the clinical efficacy between cefoperazone/sulbactam and meropenem rotation therapy for the pneumonia patients infected by ESBLs-E.coli, but the antibiotic rotation of above two antibiotic can effectively curb the production of ESBLs-E.coli and CR-E.coli.