Genomic epidemiology of antimicrobial resistance in <i>Staphylococcus aureus</i> : Analysis of 1,152 complete genomes

Objectives: Studying contemporary antimicrobial resistance ( AMR ) gene distribution in Staphylococcus aureus through comprehensive genomic surveillance analysis by characterizing the prevalence, distribution, geographical context, and co-occurrence of AMR genes in a large collection of recent S. aureus genomes. Materials and Methods: A retrospective genomic surveillance study was conducted on 1,152 complete S. aureus genomes from the National Center for Biotechnology Information RefSeq database with release dates between January 2020 and April 2025. AMR genes were identified using AMRFinderPlus. Statistical analysis: Custom Python scripts using specialized libraries for data manipulation and analysis, supplemented by R statistical software for advanced genomic epidemiology analyses, were performed to determine AMR gene prevalence, distribution, and co-occurrence relationships. Results: An overwhelming 94.27% (1,086/1,152, 95% confidence interval [92.78, 95.47]) of genomes harbored at least one AMR gene. The analysis identified 135 unique AMR genes across 25 drug classes. The tetracycline resistance gene, tet(38) , was present in 99.91% of AMR-positive genomes. The methicillin resistance gene, mecA , was detected in 50.18% of AMR-positive isolates. Acquired resistance genes were 3.3 time s more frequent than point mutations. Analysis of geographical metadata revealed high AMR rates globally, though this study provides a genotypic prediction of resistance, without phenotypic correlation, and may be influenced by sampling bias inherent in public databases, which primarily contain clinically submitted genomes. Conclusions: This study reveals a high prevalence and complex architecture of AMR genes in contemporary S. aureus populations. These findings highlight the need for enhanced global genomic surveillance to mitigate the threat of multidrug-resistant S. aureus .