Background:
Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been considered a nosocomial pathogen. However, declining MRSA prevalence in many European countries has raised questions about the relative contribution of nosocomial transmission to MRSA epidemiology in low-prevalence healthcare settings. We aimed to characterize MRSA population structure and transmission dynamics in a German tertiary care hospital.

Methods:
We conducted a retrospective genomic epidemiology study at a tertiary care hospital in Germany, including first MRSA isolates per patient and year collected between 2020 and 2024. Whole-genome sequencing and core genome multi-locus sequence typing were performed. Clusters were defined using a threshold of ≤10 allelic differences and assessed using epidemiological data.

Results:
A total of 518 MRSA isolates from individual patients were analysed, of which 70.8% were screening-derived. The most frequent sequence types (STs) were ST22, ST398, and ST225. Only 58 of 518 isolates (11.2%) formed 23 genetic clusters, which were predominantly small (median size 2). Epidemiological assessment identified links to the study hospital, households, and external healthcare facilities, whereas several clusters had no identifiable epidemiological link. Only one cluster was compatible with probable in-hospital transmission. ST398 isolates were significantly less likely to originate from clinical samples (odds ratio = 0.34; P = 0.0004) and were exclusively detected as singletons.

Conclusions:
In this low-prevalence setting, MRSA epidemiology was characterized by limited evidence of sustained nosocomial transmission despite cocirculation of multiple healthcare-associated, livestock-associated, and community-associated lineages. These findings suggest that MRSA cases are primarily driven by external introductions rather than sustained in-hospital transmission and support more targeted, lineage- and context-adapted infection prevention strategies.