MRSA Profiles Reveal Age- and Gender-Specificity in a Tertiary Care Hospital: High Burden in ICU Elderly and Emerging Community Patterns in Youth

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a devastating global health concern. Hypervirulent strains are on the rise, causing morbidities and mortalities worldwide. In tertiary care hospitals, critically ill patients, those undergoing invasive procedures, and pediatric and geriatric patients are at risk. It is not fully clear how strains adapt and specialize in humans and emerge despite the well-established commonality of the <i>S. aureus</i> genome from humans and animals. This study investigates the influence of age-, gender-, and source-specific profiles (clinical, intensive care unit (ICU vs. non-ICU)) on the evolution of hospital-associated (HA)-MRSA versus community-associated (CA)-MRSA lineages. A total of 253 non-duplicate <i>S. aureus</i> isolates were obtained from May 2023 to March 2025. The patients were stratified by age and gender in ICUs and non-ICUs. Standard microbiology methods and Clinical and Laboratory Standards Institute (CLSI) guidelines were used for identification and susceptibility testing, with cefoxitin and oxacillin disk diffusions and molecular diagnosis confirming MRSA. Mann–Whitney U and Chi-square tests assessed the demographic distributions, clinical specimen sources, and MRSA/methicillin-sensitive <i>S. aureus</i> (MSSA) prevalence. Of 253, 41.9% originated from ICUs (71% male; 29% female) and 58.1% from non-ICU wards (64% male; 36% female). In both settings, MRSA colonized the two extremes of age (10–29 and 70+) for males and females, with different mid-life peaks or declines by gender. However, the overall demographic distribution did not differ significantly between the ICU and non-ICU groups (<i>p</i> = 0.287). Respiratory specimens constituted 37% and had the highest MRSA rate (42%), followed by blood (24.5%) and wounds (10.3%). In contrast, MSSA dominated wounds (20.3%). Overall, 73.9% were resistant to cefoxitin and cefotaxime, whereas vancomycin, linezolid, daptomycin, and tigecycline remained highly effective. Younger non-ICU patients (10–29) had higher MSSA, whereas older ICU ones showed pronounced HA-MRSA profiles. By the virtue of methicillin resistance, all MRSA were classified as multidrug resistance. Thus, MRSA colonization of the two extremes of life mostly in ICU seniors and the dominance of invasive MSSA and CA-MRSA patterns in non-ICU youth imply early age- and gender-specific adaptations of the three lineages. MRSA colonizes both ICU and non-ICU populations at extremes of age and gender specifically. High β-lactam resistance underscores the importance of robust stewardship and age- and gender-specific targeting in screening. These findings also indicate host- and organ-specificity in the sequalae of MSSA, CA-MRSA, and HA-MRSA evolutionary dynamics, emphasizing the need for continued surveillance to mitigate MRSA transmission and optimize patient outcomes in tertiary care settings.