Global epidemiological insights on the antimicrobial resistance of Enterococcus faecium and a genomic analysis framework

<i>Enterococcus faecium</i> is a pathogen that frequently causes infections and outbreaks in hospitals. Despite the increasing need for genomic surveillance of <i>E. faecium</i>, a standardized genomic analysis framework for this pathogen is lacking. We aim to conduct a comprehensive global epidemiological overview and propose a genomic analysis framework. We analysed 21,058 public <i>E. faecium</i> genomes from 80 countries to create a comprehensive snapshot of <i>E. faecium</i> resistome and virulence in association with geography and population structure. We compared strain clustering based on SNP-based and sequence typing-based approaches with ST80 genomes as examples, to establish the methodological comparability for outbreak investigations using different approaches. Focusing on the resistance genotypes against vancomycin and linezolid, we observed within-sequence type (ST) dynamics, such as a <i>vanA</i>-to-<i>vanB</i> transition within ST80 isolates in Denmark driven by the clonal expansion and dissemination of mobile linezolid resistance among ST22 and ST32. We established that the popularly used 25 allele distance threshold based on core genome multi-locus sequence typing corresponds to 86 core genome SNPs or 380 whole-genome SNPs. Finally, we introduce <i>GenoFaecium</i>, a user-friendly analytical tool to streamline the genomic surveillance of <i>E. faecium</i>, which enables consistent interpretation of antimicrobial resistance and virulence profiles from <i>E. faecium</i> genome sequences. By providing this tool and empirically bridging the outbreak investigation thresholds of different phylogenetic methods, our study facilitates and improves the genomic surveillance of <i>E. faecium</i>.