Clinical outcomes of empirical anti-MRSA therapy at a tertiary care center in Madinah, Saudi Arabia: a retrospective single-center cohort study

Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in Saudi Arabia, posing a significant clinical challenge. International guidelines recommend empirical anti-MRSA coverage for high-risk patients. This study aimed to describe the real-world use of empirical anti-MRSA therapies and explore associated clinical outcomes among hospitalized adults at a single tertiary center in Saudi Arabia. We conducted a retrospective cohort study of 323 adult patients who received empirical intravenous anti-MRSA therapy (linezolid, vancomycin, or teicoplanin) between June 2021 and June 2025. The primary endpoint was in-hospital mortality. Secondary endpoints included clinical improvement, length of stay, adverse events, and changes in laboratory measures. Multivariable logistic regression was used to identify independent predictors of mortality. The cohort had a mean age of 70.97 years, and 51.70% had started empirical anti-MRSA during ICU stay. Overall, the in-hospital mortality rate was 39.01%. Mortality rates did not differ significantly between treatment groups: 42.57% for linezolid, 35.82% for vancomycin, and 57.89% for teicoplanin (p = 0.121). Changes in C-reactive protein varied significantly (p = 0.009), with levels decreasing in the linezolid and vancomycin groups but increasing in the small teicoplanin group. Vancomycin was associated with a higher reported incidence of acute kidney injury than linezolid and teicoplanin (3.00% vs. 0.99% and 0.00%, respectively). In multivariable analysis, older age (OR 1.05, p < 0.001) and male sex (OR 1.81, p = 0.032) were significant risk factors for mortality. Non-ICU admission was associated with a lower mortality rate (OR 0.45, p = 0.004). In this real-world cohort of patients receiving empirical anti-MRSA therapy, we found no significant difference in in-hospital mortality or clinical improvement between linezolid, vancomycin, and teicoplanin. Patient outcomes were primarily driven by underlying factors like age and illness severity rather than the choice of antibiotics. Vancomycin was associated with a higher incidence of reported acute kidney injury. The findings highlight the need for improved antimicrobial stewardship to guide appropriate empirical therapy.