OBJECTIVES: To examine the impact of pathogen spectrum and antibiotic resistance on the treatment efficacy of clinical microbial infections from 2012 to 2022. METHODS: Retrospective analysis of clinical data from 1200 patients with microbial infections admitted to The Fifth Hospital of Xiamen. Bacterial cultures and drug sensitivity tests were conducted, and the efficacy of first-line antibiotics was evaluated. RESULTS: A total of 1258 pathogens were identified, with 57.23% Gram-positive and 37.84% Gram-negative bacteria. Staphylococcus aureus and Staphylococcus epidermidis showed high resistance to penicillin and cephalosporins. Klebsiella pneumoniae and Escherichia coli exhibited elevated resistance to imipenem and cephalosporins. From 2018 to 2022, there was an increase in resistance to cephalosporins and a decrease in treatment efficacy ( CONCLUSIONS: Rising resistance rates to cephalosporins among Gram-positive and Gram-negative bacteria have led to diminished antibiotic efficacy. Adjustments in antibiotic selection, such as using glycopeptide antibiotics, are needed to combat resistance.