Hospital-Onset Bloodstream Infections: Progressive Shift from Methicillin-Resistant Staphylococcus aureus to Methicillin-Susceptible Staphylococcus aureus over 11 Years

Background: Staphylococcus aureus bloodstream infections cause substantial hospital mortality (20–50%). Surveillance programs primarily focus on methicillin-resistant S. aureus (MRSA) as a quality indicator, while comprehensive data comparing MRSA and methicillin-susceptible S. aureus (MSSA) hospital-onset bacteremia remain limited outside the UK, the USA, and Canada. This study aims to evaluate incidence trends of all hospital-onset S. aureus bloodstream infections (HO-SABSIs, defined as positive blood cultures ≥ 48 h post-admission) from 2013 onwards, comparing MRSA and MSSA incidence patterns and their associated mortality rates in an Italian tertiary-care hospital through surveillance data. Methods: Retrospective cohort study of all HO-SABSIs from January 2013 to December 2023 at a 458-bed Italian tertiary hospital. Primary outcome was incidence density (cases per 1000 patient-days) stratified by methicillin resistance. Standardized Infection Ratios (SIRs) were calculated using 2013–2015 and 2013–2019 as baseline periods. Temporal trends were analyzed using negative binomial regression. Results: Among 414 HO-SABSI cases, 183 (44.2%) were MRSA and 231 (55.8%) MSSA. MRSA incidence decreased significantly (−6.5% annually; IRR 0.935, 95%CI 0.883–0.991; p = 0.023) from 0.198 to 0.111 per 1000 patient-days. MSSA increased non-significantly (+4.9% annually; IRR 1.049, 95%CI 0.999–1.103; p = 0.056) from 0.103 to 0.239, surpassing MRSA after 2016 and peaking during COVID-19 (2021: SIR 2.41, 95%CI 1.33–4.37). MRSA cases had higher mortality than MSSA (40.6% vs. 27.5%; p = 0.005). Conclusions: MSSA has replaced MRSA as the predominant hospital-onset S. aureus bacteremia pathogen since 2016, with sustained elevation during and after the COVID-19 pandemic. Current MRSA-focused surveillance misses the majority of preventable staphylococcal bacteremias. Comprehensive hospital-onset S. aureus surveillance encompassing both phenotypes is essential for accurate epidemiological assessment and infection prevention.