Hospital outbreaks with vancomycin-resistant enterococci (VRE) pose a serious health threat and a challenge to infection prevention and control (IPC). We herein report on a VRE outbreak of unprecedented extent in Southern Germany (October 2015–November 2019). We used descriptive epidemiology and whole-genome sequencing (WGS) for a detailed outbreak investigation. Of the 2905 cases, 2776 (95.3%) were colonized, whereas from 127 (3.7%), VRE could be isolated from otherwise sterile body fluids or sites unlikely for enterococci colonization. Cases had a median age of 78 years (IQR 68–84) and 1339/2905 (46%) were female. The majority of isolates sequenced belonged to the clonal lineage ST80/CT1013 (212/397, 53%). Nosocomial transmission was observed as well as the constant import of VRE into the hospital. Extensive IPC measures were implemented and terminated the outbreak in late 2019, eventually. Our study shows that the combination of epidemiological and genomic analyses is indispensable for comprehensive outbreak investigations. The adaptation of IPC measures to these findings, their timely implementation, and strict execution also allow containment of large VRE outbreaks in hospital settings.
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