Predicting antimicrobial resistance in Staphylococcus aureus using machine learning: Insights from a five-year surveillance study.

Staphylococcus aureus is a leading cause of both community- and hospital-acquired infections, and the growing prevalence of antimicrobial resistance complicates clinical management worldwide. This study investigated the epidemiology, resistance trends, multidrug resistance (MDR) patterns, and the role of machine learning (ML) in predicting antibiotic susceptibility in Saudi Arabia. A total of 18,003 microbiology reports (2019-2024) were analyzed, identifying 2506 S. aureus isolates. Susceptibility testing included 31 antibiotics representing 11 pharmacological classes. Predictive ML models (Random Forest, Logistic Regression, Gradient Boosting) were trained and evaluated using accuracy, precision, recall, F1-score, and confusion matrices. Wound (24 %) and blood (23 %) were the most frequent sources of S. aureus. High resistance (>70 %) was observed for β-lactams, fluoroquinolones, and macrolides/lincosamides, while glycopeptides, oxazolidinones, and lipopeptides maintained excellent activity (<10 % resistance). MDR occurred in 30 % of isolates, XDR in 0.6 %, and no PDR isolates were detected. Among ML models, Random Forest achieved the best overall performance across most antibiotics, Logistic Regression was optimal for ampicillin, and Gradient Boosting for linezolid. Vancomycin, linezolid, penicillin, and SXT achieved precision and recall above 0.92, demonstrating strong predictive reliability. S. aureus remains a major clinical threat in Saudi Arabia, with high MDR rates but preserved efficacy of last-line antibiotics. This study highlights the value of combining multi-center surveillance with interpretable machine learning approaches to support antimicrobial stewardship, enhance early resistance prediction, and inform data-driven clinical decision-making, particularly in settings where rapid molecular diagnostics may be limited.