Trends, Seasonality, and the Impact of COVID-19 on Clinical Staphylococcus aureus and MRSA Isolates in Western Mexico (2016–2025): A Time-Series Analysis at a University Referral Hospital

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) remains a major cause of both community-onset and hospital-acquired infections, yet longitudinal data from Latin American hospitals spanning the COVID-19 pandemic are scarce. We characterized temporal trends, seasonality, and the impact of the COVID-19 pandemic on MRSA prevalence and incidence density among clinical S. aureus isolates at a tertiary-care hospital in western Mexico over 9.5 years. Methods: We analyzed 6625 non-duplicate clinical S. aureus isolates (6609 with valid resistance data) from June 2016 to December 2025. Temporal trends were assessed using Mann–Kendall tests, Theil–Sen estimation, and binomial generalized linear models. Seasonality was evaluated through STL decomposition, generalized additive models, and Fourier analysis. An interrupted time series (ITS) model with GLS-AR(1) and Newey–West corrections compared three COVID-19 phases: pre-pandemic (2016–2020), high viral circulation (2020–2022), and post-peak stabilization (2022–2025). Exposure-adjusted incidence densities (per 1000 patient-days) were analyzed in parallel. Results: MRSA prevalence declined from 28.1% pre-pandemic to 14.0% post-peak (Mann–Kendall z = −9.03, p < 0.001; OR = 0.85 per year, 95% CI: 0.829–0.871). MRSA incidence density decreased by 50%, from 1.27 to 0.63 per 1000 patient-days, while aggregate S. aureus incidence density remained stable (z = −0.17, p = 0.868). The ITS joint Wald test confirmed a significant cumulative shift in MRSA trajectory post-pandemic (p = 0.019 counts; p = 0.012 incidence density), with a significant post-peak level drop (p = 0.008). S. aureus exhibited moderate seasonality peaking in May–July (GAM edf = 7.26, p < 0.001), whereas MRSA showed only marginal seasonal variation. Conclusions: MRSA declined markedly across the study period, with the steepest reduction following the Omicron peak. The decline persisted after adjustment for pandemic-related fluctuations in hospital volume, supporting periodic reassessment of empiric anti-MRSA prescribing policies in similar settings.