Objective To explore the distribution characteristics of clinical main isolated bacteria and drug resistance status of Klebsiella pneumoniae in a Guangxi hospital in 2022. Methods Blood, sputum, urine, secretions, and other clinical samples of inpatients in a Guangxi hospital from January to December 2022 were collected, and after performing isolation and culture of pathogenic bacteria on them, the bacterial identification and drug sensitivity test were carried out to analyze clinical distribution characteristics of main isolated bacteria and drug resistance status of Klebsiella pneumoniae. Results A total of 4349 strains of bacteria were isolated, mainly from the samples of clean midstream urine, sputum, wound specimen, whole blood, alveolar lavage fluid, etc. The departments with high proportion of isolated bacteria were critical care medicine, respiratory and critical care medicine, transplantation medicine center, urology, and endocrinology, etc. Among which, Gram⁃negative bacteria accounted for 71.76% (3121/4349), and the top five isolation rates were Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii (complex), and Stenotrophomonas maltophilia. Gram⁃positive bacteria accounted for 28.24% (1228/4349), and the top five isolation rates were Staphylococcus aureus (complex), Enterococcus faecium, Enterococcus faecalis, Staphylococcus haemolyticus and Staphylococcus epidermidis. The drug resistance rate of Klebsiella pneumoniae to nitrofurantoin, tetracycline, cefazolin, and other medicines was relatively high, and the drug resistance rate to tigecycline, ceftazidime/avibactam, and polymyxin was low. A total of 91 strains of carbapenem⁃resistant Klebsiella pneumoniae were detected, mainly from the departments of rehabilitation medicine, critical care medicine, transplantation medicine center, and respiratory and critical care medicine, etc. Conclusion Klebsiella pneumoniae is common in clinical practice, and its drug resistance is relatively serious. In clinical practice, it is necessary to strengthen the monitoring of Klebsiella pneumoniae, especially carbapenem⁃resistant Klebsiella pneumoniae, rationally use antibiotics, and formulate targeted prevention and control measures to avoid the weakening of efficacy caused by drug resistance.