Genomic Epidemiology of Enterococcus faecium Bloodstream Infections During a VanB-type VRE Peak Reveals an Oligoclonal Scenario: An Observational Study at a German University Hospital (2017–2022)

Background: A substantial and rapid increase, followed by a sharp decline in vanB-type vancomycin-resistant E. faecium (VRE), occurred in Germany in the late 2010s. This unusual epidemiological trend prompted detailed genomic investigations to explore the underlying dynamics at a German university hospital. Methods: We retrospectively analyzed E. faecium bloodstream infection (BSI) isolates collected between 2017 and 2022. Isolates were classified as vanA-positive, vanB-positive, or van-negative. Molecular typing included multilocus sequence typing (MLST), core genome MLST (cgMLST), and split k-mer analysis (SKA). Clonal relationships and potential patient-to-patient transmission events were assessed by integrating genomic data with machine-aided analysis of available longitudinal patient movement data. Results: High-resolution genomic analysis of BSI isolates revealed an oligoclonal scenario involving multiple epidemic lineages (e.g., sequence type (ST)117/ complex type (CT)71, ST117/CT929, ST117/CT2505, ST80/CT467, ST80/CT1470) with distinct van genotypes and dynamic changes over time. Overall, genomic overlap between vanA-positive, vanB-positive, and van-negative populations was minimal. The observed vanB peak in 2018-2/ 2019-1 was mainly driven by ST117/CT71, ST117/CT36 and ST117/CT1917. SKA provided enhanced discriminatory power over cgMLST. Potential transmission events were characterized by prolonged intervals between infections and repeated intra-hospital transfers. Conclusions: Accurate depiction of the epidemiological dynamics during the transient vanB-type VRE peak required an integrated genomic approach, combining cgMLST with high-resolution SKA, and epidemiological analyses. Such comprehensive approaches are essential for realistic interpretation and precise adjustment of infection prevention and control strategies. Future prospective studies incorporating comprehensive patient-movement and environmental data could further enhance our understanding of how infection control measures, clonal expansion, and host factors jointly shape VRE epidemiology.