Strengthening knowledge through surveillance and research is one of the main steps in treating antibiotic-resistant infections. The present study was therefore designed to analyse long-term antimicrobial resistance trends over the 12 years in Iran. Data from the patient's clinical specimens were collected over 12 years from January 2012 until December 2023. Antimicrobial susceptibility patterns of gram-positive bacteria (GPB) were identified using the Kirby-Bauer disk diffusion method (DDM) and resistance proportions to most commonly used antibiotics were calculated for each GPB. All data were analysed using descriptive statistics. A total of 30,548 cultures were positive for GPB. Staphylococcus aureus (S. aureus) with 59.5% and coagulase-negative staphylococci (CoNS) with 26.6% frequently isolated from blood specimens. S. aureus was the frequently isolated organism in ≥ 6 years of age groups. S. aureus isolates showed the highest and lowest resistance rates to penicillin (91.8%) and vancomycin (1.1%), respectively. Nitrofurantoin (10.5%) was the most effective antimicrobial agent on Enterococcus spp. Time trends in antibiotic resistance revealed a sharp increase for several antibiotics: from 33.9% in 2013 to 54.5% in 2023 for gentamicin
from 51.2% in 2013 to 76.4% in 2023 for ceftriaxone
from 34.5% in 2013 to 54.8% in 2023 for imipenem
and from 66.7% in 2012 to 81.8% in 2023 for cefixime. The present research suggests that vancomycin and nitrofurantoin are effective antibiotics against infections caused by Staphylococcus and Enterococcus spp., respectively. This data revealed that the continuous monitoring of antimicrobial resistance (AMR) patterns is necessary for selecting the suitable drug.