Global epidemiology and genomic perspectives on vancomycin-resistant Enterococcus faecium: Rising antimicrobial...

Vancomycin-resistant Enterococcus faecium (VREfm) can be detected in the intestines of humans and animals, as well as in various environments. As multidrug resistant bacteria, E. faecium causes infections that are difficult to treat and pose a significant threat to public health. In this study, we analyzed 1632 vanA or vanB-positive isolates from Homo sapiens, animals, natural environments, and hospital environments across 49 countries. MLST analysis revealed a total of 127 different sequence types, with notably higher sequence type (ST) diversity observed in the United States. ST117 and ST80 were the most common VREfm sequence types and should be continuously monitored in future surveillance programs. Phylogenetic analysis revealed a potential risk of clonal transmission in VREfm. Furthermore, genomic clustering via split k-mer and core genome SNP analyses identified cross-species, cross-border, and nosocomial transmission clusters, confirming multidirectional spread. Bioinformatics analyses revealed 68 antibiotic resistance gene (ARG) subtypes, predominantly conferring resistance to glycopeptides, aminoglycosides, and multiple classes of antibiotics. Temporal analysis revealed a 42 % increase in the average number of ARGs per isolate over three decades, along with the emergence of novel resistance genes, indicating a persistent increase in antimicrobial resistance. Geographical and source-based differences were observed in the number of antibiotic resistance gene subtypes. Specifically, H. sapiens isolates carried significantly more ARGs than did their animal or environmental counterparts (p < 0.001), whereas isolates from low-income countries presented a greater ARG burden than did those from high-income regions (p < 0.05). Mobile genetic elements, particularly plasmids, were strongly correlated with the number of ARGs (p < 0.001), as validated through explainable artificial intelligence. In conclusion, this study emphasizes the importance of monitoring and exploring the evolution of VREfm strains, particularly changes in antibiotic resistance genes and the spread of these strains, within the "One Health" framework. Moreover, heightened vigilance in epidemiological surveillance and infection control practices is necessary.