Staphylococcus aureus is a versatile and opportunistic pathogen implicated in a wide spectrum of infections, ranging from minor skin and soft tissue conditions to severe, invasive diseases such as pneumonia, endocarditis, osteomyelitis, and bloodstream infections (Tong et al., 2015). The global escalation of antimicrobial resistance, particularly the emergence and spread of methicillin-resistant S. aureus (MRSA), has transformed the clinical practice, posing significant challenges to treatment, infection control, and public health management (Gurung et al., 2020; Bereanu et al., 2024).

While methicillin-susceptible S. aureus (MSSA) remains responsive to beta-lactam antibiotics, MRSA exhibits resistance to multiple drug classes, including beta-lactams, macrolides, and fluoroquinolones (Vestergaard et al., 2019). This multidrug-resistant phenotype has contributed to higher rates of morbidity, mortality, and healthcare costs (Abebe and Birhanu, 2023; Kumar et al., 2025). The emergence of MRSA has led to an increased reliance on last-line agents such as vancomycin and linezolid, further complicating therapeutic decisions and antimicrobial stewardship (Kumar et al., 2025).

A meta-analysis from Egypt reported a pooled MRSA prevalence of approximately 67% among Staphylococcus aureus clinical isolates, mainly collected from hospitals and healthcare facilities, including blood, respiratory specimens, wound swabs, and urine (Azzam et al., 2023). In a systematic review and meta-analysis of 119 studies from 29 countries, the pooled global MRSA prevalence of 14.7% (95% CI: 12.4–17.2%) among residents of elderly care centers. This study emphasized the high prevalence of MRSA in these settings and the need for targeted infection control measures (Hasanpour et al., 2023).A systematic review and meta-analysis of 40 studies across 20 countries reported a global MRSA prevalence of 17% (95% CI: 14–27%) in diabetic foot ulcer patients. The prevalence declined from 25% before 2010 to 9% after 2021. Regionally, it was highest in South America (61%), followed by North America (20%), Europe (19%), and Africa (13%) (Zhou et al., 2024). In China, the prevalence of MRSA has shown a notable decline over recent years. A study published in Scientific Reports reported a decrease in the proportion of MRSA from 69% in 2005 to 44.6% in 2014 (Zhen et al., 2020).

In Saudi Arabia, the epidemiology of MRSA has demonstrated considerable regional variability. National estimates suggest that MRSA accounts for approximately 35% to 45% of all S. aureus isolates, with higher rates reported in hospital settings (El Amin and Faidah, 2012; Alanzi et al., 2024; Almutairi et al., 2024). A systematic review covering data from 2002 to 2012 documented an overall MRSA prevalence of 35.6% (Yousef et al., 2013). Regional variations are notable. A 2019 study indicated that the Western region, which includes the Asir region, had a MRSA prevalence rate of 42%, higher than the Central (32%) and Eastern (27%) regions (Adam and Abomughaid, 2018). Studies from Riyadh have reported that 27% to 33% of Staphylococcus aureus isolates were MRSA (Baddour et al., 2006), while research from Jeddah found the rate to be around 40% (Madani, 2002).

MRSA is particularly prevalent in hospital-associated infections (HAIs), especially in intensive care units (ICUs), where rates have been reported as high as 60% to 80% (Madani, 2002; Ali et al., 2020). In contrast, MSSA remains more prevalent in community-acquired infections and is a significant contributor to S. aureus disease burden. MSSA is typically associated with lower resistance profiles and better treatment outcomes. However, its proportion among S. aureus isolates has gradually declined in many regions due to the rise of MRSA. In the Asir region, the dominance of MRSA in hospital settings underscores an urgent need for targeted infection control and surveillance efforts (Hamid, 2011). A study reported that hospital-acquired MRSA represents 54% of all nosocomial infections caused by S. aureus clinical isolates in the Asir Province, with 85% of these strains being multidrug-resistant (Alanzi et al., 2024).

According to a recent systematic analysis conducted in 2024, which included more than 16,000 samples from 24 studies across the Kingdom, the average MRSA prevalence was 17.0% (random effects) and 8.6% (fixed effects).

These studies demonstrate the importance of having local epidemiology data to understand resistance patterns and guide strategic interventions. Given the increasing incidence of MRSA in both healthcare and community environments, ongoing surveillance is critical (Samuel et al., 2023). Monitoring temporal resistance patterns enables clinicians and public health officials to adapt empiric therapy protocols, reinforce antimicrobial stewardship, and develop regionally appropriate guidelines for infection prevention and control (Pezzani et al., 2020).

This study aimed to describe the epidemiological and microbiological characteristics of S. aureus infections, focusing on the comparative prevalence of MRSA and MSSA isolates across different clinical settings and comorbidities. We also investigated the trends in oxacillin resistance over 11 years (2013–2024), evaluating the temporal progression and the specific healthcare environments where MRSA has become increasingly prevalent. These findings are expected to provide crucial insights that support targeted antimicrobial stewardship and guide infection control policies tailored to regional needs.

A total of 4,267 non-duplicate Staphylococcus aureus isolates were included in the analysis, comprising 2,250 (52.7%) MRSA and 2,017 (47.3%) MSSA. The mean age of patients was 49.3 ± 22.4 years, with no significant difference observed between the MRSA and MSSA groups (p = 0.175). Males accounted for 70.8% of the study population, and although a slightly higher proportion was noted among MRSA cases (53.3%), the difference was not statistically significant (p = 0.281) ( Table 1 ).

MRSA was significantly associated with certain clinical diagnoses, including urinary tract infections (62.5%), COVID-19 (62.5%), diabetes mellitus (56.4%), and ESRD (52.7%) (p = 0.041) ( Table 2 ).

Inpatient status also correlated with higher MRSA prevalence (54.1%, p < 0.001; Fisher's exact test). Across hospitalization wards, MRSA was more frequently isolated in surgical (56.0%), ICU/IMCU (53.4%), and medical (52.7%) wards compared to MSSA, with statistically significant differences (p < 0.001) ( Figure 1 ).

The distribution of culture sources did not differ significantly between MRSA and MSSA isolates (p = 0.212); however, MRSA was more frequently recovered from cerebrospinal fluid (56%), blood (55.0%), skin and soft tissue (53.8%), and abscess samples (55.1%) ( Figure 2 ).

MRSA prevalence demonstrated a statistically significant upward trend across all hospital wards over the study period. In surgical wards, the proportion of MRSA isolates increased from 46.6% in 2013 to 68.3% in 2024 (OR = 1.115; 95% CI: 1.080–1.152; p < 0.001). Comparable increases were observed in medical wards (OR = 1.066; p < 0.001), IMCU/ICU units (OR = 1.050; p = 0.021), and outpatient settings (OR = 1.112; p < 0.001) ( Figure 3 ).

This study presents a 12-year analysis of Staphylococcus aureus infections, with particular emphasis on the evolving epidemiology of MRSA in comparison to MSSA within a tertiary care center. The findings demonstrate a sustained and concerning rise in MRSA prevalence, aligning with both national and international epidemiological trends.

In our study, we confirmed all MRSA isolates by detecting the mecA gene with the GeneXpert MRSA assay. We also confirmed 100 randomly selected isolates as positive for the SCCmec gene. These findings match global reports, where mecA is the main cause of methicillin resistance in S. aureus and is nearly always found in MRSA strains. For instance, studies from Europe, Asia, and North America show mecA positivity among MRSA isolates (Becker et al., 2016; Idrees et al., 2023; González-Vázquez et al., 2024). The detection of SCCmec elements further highlights their role in spreading resistance. Hospital-associated lineages often carry larger SCCmec types (I–III), while community-associated strains are usually related to smaller, more mobile types (IV and V) (González-Vázquez et al., 2024).

The overall MRSA prevalence in this study (52.7%) surpasses earlier estimates from Saudi Arabia, where a systematic review reported MRSA rates ranging from 35.6% to 45% in various regions between 2002 and 2012 (El Amin and Faidah, 2012; Alanzi et al., 2024). Our observed rate aligns closely with more recent reports from the Asir region, where MRSA prevalence in nosocomial S. aureus infections was noted to be approximately 54% (Hamid, 2011). Similarly, a study conducted in Taif (Mecca Province) reported that nosocomial infections accounted for 48% of all S. aureus infections among hospitalized patients, while community-associated infections comprised 52% (Sabra and Abdel-Fattah, 2012). This suggests that the burden of MRSA in the Asir region may be higher than the national average, which reflects a broader trend of increasing resistance, particularly in hospital settings.

Globally, MRSA prevalence varies widely, from 20%–30% in northern Europe to over 50% in parts of Asia and the Middle East (World Health Organization, 2014). Studies from neighboring Gulf countries, such as the United Arab Emirates and Kuwait, report MRSA prevalence rates between 22% and 55%, indicating that Saudi Arabia’s MRSA burden is comparable to regional figures (Udo and Boswihi, 2017; Al-Saleh et al., 2022; Thomsen et al., 2023).

Importantly, our study demonstrated no significant differences in MRSA prevalence by age or sex, consistent with findings from other studies in Saudi Arabia and internationally (Madani et al., 2001; Iyer et al., 2014). However, MRSA infections were significantly associated with specific risk factors, particularly COVID-19 (62.5%), diabetes mellitus (56.4%), and end-stage renal disease (52.7%) (p = 0.030). Similar associations have been noted in global studies, where MRSA is increasingly implicated in infections among immunocompromised and chronically ill patients (Zacharioudakis et al., 2014; Garoy et al., 2019; Samuel et al., 2023).

Hospitalization settings significantly influenced the prevalence of MRSA. According to our findings, the percentage of MRSA in inpatients was substantially higher (54.1%, p < 0.001), especially in surgical wards (56.0%), ICU/IMCU units (53.4%), and medical wards (52.7%). This is consistent with previous Saudi research, which identified ICUs as high-risk environments, with MRSA frequencies ranging from 40% to 60% in certain tertiary institutions (Ali et al., 2020; Taha et al., 2022; Alanzi et al., 2024; Almutairi et al., 2024). This indicates that the MRSA rates in ICUs are still extremely high worldwide; at some facilities, they surpass 50% of S. aureus isolates (Lee and Harbarth, 2012; CDC, 2024).

Regarding culture sources, although there was no statistically significant difference between MRSA and MSSA isolation sites (p = 0.212), MRSA was more frequently recovered from blood (55.0%), skin and subcutaneous (53.8%), and abscess samples (55.1%). This non-specific distribution agrees with global patterns, reinforcing MRSA’s versatility in causing localized and systemic infections (Turner et al., 2019; Siddiqui and Koirala, 2025).

Temporal analysis revealed a statistically significant increase in MRSA prevalence across all hospital wards, with the surgical ward showing the most dramatic rise from 46.6% in 2013 to 68.3% in 2024 (OR = 1.115, 95% CI: 1.080–1.152, p < 0.001). Similarly, upward trends were noted in medical and ICU settings. These findings are concerning but not unexpected, given rising antibiotic resistance, prolonged hospitalizations, and the intensive use of medical devices in such environments (Lee and Harbarth, 2012; Sabra and Abdel-Fattah, 2012; Lee et al., 2021; Samuel et al., 2023).

Notably, our data corroborate recent reports indicating that MRSA rates—particularly hospital-associated strains—remain a significant concern in Saudi Arabia despite ongoing infection control efforts. A 2024 meta-analysis indicated regional MRSA prevalence rates of up to 42% in western regions of Saudi Arabia, including Asir, highlighting persistent challenges (Alanzi et al., 2024).

The COVID-19 pandemic may have further complicated infection control measures, as suggested by the high MRSA rates observed among COVID-19 patients in this study (62.5%). Emerging evidence suggest that COVID-19, particularly when accompanied by immunosuppressive treatments and invasive mechanical ventilation, may increase the risk of secondary MRSA infections (Pintea-Simon et al., 2024).

Strengths of this study include its large sample size, longitudinal design, and detailed analysis by clinical setting and diagnosis. However, some limitations must be acknowledged: the retrospective design limits causal inference, molecular typing of MRSA strains was not performed, and data were drawn from a single tertiary center, potentially limiting generalizability.

The results of this study provide a detailed analysis of the epidemiological and microbiological characteristics of Staphylococcus aureus infections over 11 years, highlighting the comparative prevalence of MRSA and MSSA across diverse clinical settings and patient comorbidities. The results reveal a steadily increasing burden of MRSA, particularly within inpatient hospital wards and among vulnerable populations such as those with urinary tract infections, diabetes mellitus, COVID-19, and end-stage renal disease.

The observed rise in oxacillin resistance across all healthcare environments underscores the critical need for strengthened infection control measures and tailored antimicrobial stewardship programs. Continuous local surveillance is essential for monitoring resistance patterns, adapting empirical therapy guidelines, and preventing further dissemination of MRSA strains.

Future efforts should focus on implementing robust national infection prevention strategies, promoting rational antibiotic use, and investing in molecular epidemiology research to understand transmission dynamics. Strengthening healthcare infrastructure, particularly in high-risk hospital wards, and enhancing community-level awareness will be pivotal in controlling the growing MRSA threat in Saudi Arabia and similar regions.