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)
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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, and ST262) with distinct van genotypes and dynamic changes over time. Overall, genomic overlap between vanA -positive, vanB -positive, and van -negative populations was minimal. The vanB surge, peaking in late 2018-early 2019, was mainly driven by ST117/CT71, ST117/CT36, and ST117/CT1917. SKA provided enhanced discriminatory power over cgMLST. Prolonged intervals between infection onsets and frequent intra-hospital transfers were characteristic of potential transmission events.
Conclusions
Accurate characterization of the transient vanB -type VRE peak required an integrated genomic approach combining cgMLST, high-resolution SKA, and epidemiological data. These comprehensive methods enable infection prevention and control (IPC) teams to distinguish true outbreaks from numerical clusters of polyclonal isolates. This allows for accurate interpretation and precisely targeted interventions where evidence supports transmission.
Importance
Vancomycin-resistant Enterococcus faecium is an increasingly important nosocomial pathogen worldwide. Understanding its epidemiology and transmission dynamics is critical to effectively control its spread. This study documents shifting E. faecium populations within a high-risk hospital environment, including both vancomycin-resistant and vancomycin-susceptible bloodstream isolates. Detailed genomic analyses, combining core genome multilocus sequence typing with high-resolution split k-mer analysis, integrated with comprehensive epidemiological tracking, were critical to accurately depict complex epidemiological dynamics. This combined approach allows precise differentiation between monoclonal outbreaks and oligoclonal transmission, enabling more targeted infection prevention and control strategies.
