This paper aims to study the distribution and drug sensitivity of pathogenic bacteria in patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary infection, so as to provide the basis for the correct use of clinical antibiotics. 1 500 strains of pathogenic bacteria were randomly selected from sputum culture samples of patients with COPD complicated with pulmonary infection in a hospital in Changsha from March 2017 to February 2022 for culture identification and drug sensitivity test. The distribution of pathogenic bacteria and the drug resistance characteristics and trends of the main Gram-negative bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) were counted and analyzed. A total of 1 251 strains (83.40%) of Gram-negative bacteria were detected from 1 500 pathogenic bacteria, of which 384 strains (25.60%) were Klebsiella pneumoniae, 333 strains (22.20%) were Pseudomonas aeruginosa, and 303 strains (20.20%) were Acinetobacter baumannii were the top. 126 strains of Gram-positive bacteria (8.40%) were detected from 1 500 pathogenic bacteria, of which 69 strains of Staphylococcus aureus (4.60%) and 27 strains of Streptococcus pneumoniae (1.80%) were the top. 123 strains of fungi (8.20%) were detected from 1 500 pathogenic bacteria, mainly 96 strains of Candida albicans (6.40%). The results of drug sensitivity analysis showed that the change of drug resistance rate of Klebsiella pneumoniae to Gentamicin, Levofloxacin, Ceftazidime and Aztreonam was statistically significant (P<0.05). The drug resistance trend of Pseudomonas aeruginosa to Aztreonam was statistically significant (P<0.05). Acinetobacter baumannii showed a high resistance rate to most antibiotics, and the resistance trend to Levofloxacin, Cotrimoxazole and Meropenem is statistically significant (P<0.05). Anti-infection is an important measure in the treatment of COPD, and timely and correct selection of sensitive antibiotics is the key link. This study provides help for the clinically accurate selection of appropriate antibiotics for the treatment of COPD, and also helps to understand the development trend of bacterial resistance in this region, which has important clinical value and significance.