Methicillin resistance and antimicrobial non-susceptibility trends among Staphylococcus aureus clinical isolates in Aseer, Saudi Arabia (2013–2024): A retrospective laboratory-based surveillance study

Background Staphylococcus aureus is a leading cause of infection, and methicillin-resistant S. aureus (MRSA) is a high-priority resistance threat. MRSA and methicillin-susceptible S. aureus (MSSA) differ in non-β-lactam resistance, yet longitudinal data from Aseer, Saudi Arabia are limited. We characterized methicillin-resistance and non-susceptibility trends to inform local stewardship. Methods We conducted a retrospective laboratory-based surveillance study of 4,194 S. aureus isolates from 3,122 patients (aged ≥12 years) at a tertiary-care center in Aseer, Saudi Arabia (January 2013–June 2024). Isolates were classified as MRSA or MSSA by oxacillin/cefoxitin testing to CLSI standards. We estimated annual non-susceptibility proportions and their temporal trends, compared non-susceptibility between MRSA and MSSA, and identified independent predictors of MRSA in a multivariable model accounting for repeated isolates from the same patient. Results MRSA accounted for 2,231 isolates (53.2%; 95% CI 51.7–54.7) and MSSA for 1,963 (46.8%); most isolates were from inpatients, including 1,975/2,231 MRSA isolates (88.5%) and 1,648/1,963 MSSA isolates (84.0%). The MRSA share rose from 47.4% (2013) to 60.4% (2024), each later year being independently associated with MRSA (adjusted OR 1.09/year, 95% CI 1.06–1.12). MRSA was significantly more non-susceptible than MSSA to penicillin, ciprofloxacin, levofloxacin, erythromycin, clindamycin, gentamicin, trimethoprim–sulfamethoxazole, tetracycline, fusidic acid and rifampin (all FDR-adjusted p < 0.05), with the widest gap for fusidic acid (62.7% vs 25.0%); fusidic-acid and fluoroquinolone non-susceptibility also increased over time. No vancomycin or daptomycin non-susceptibility was detected; teicoplanin non-susceptibility was low but significantly higher in MRSA (2.8% vs 1.5%), and low-level linezolid non-susceptibility (1.5% vs 1.3%) was not confirmatory-tested. Conclusions In this single-center Aseer surveillance, MRSA became the majority of S. aureus during 2013–2024 and showed broad multidrug non-susceptibility, while vancomycin and daptomycin retained full in vitro activity. These local findings support sustained laboratory-based surveillance, Aseer-tailored empirical and stewardship guidance, and confirmatory testing of the emerging low-level linezolid non-susceptibility signal.