Escalating threat of vanA vancomycin-resistant Enterococcus revealed through integrated statewide genomic surveillance in Australia

Abstract vanA vancomycin-resistant Enterococcus faecium (VREfm) is a major healthcare-associated pathogen. Following notification of vanA VRE in Victoria, Australia, statewide genomic surveillance enabled longitudinal characterisation of the VREfm population. We analysed 1618 vanA VREfm isolates collected over nearly six years. Overall, 85% of isolates belonged to a genomic cluster, several of which persisted over multiple years and were detected across multiple health networks. ST1424 and ST1421 predominated, while ST817 and ST1478 emerged recently. Genetic resistance determinants associated with last-line antimicrobials were identified in 18.5% of isolates, including expansion of a linezolid-resistant ST817 clone across five health networks. Long-read sequencing identified pELF-like plasmids carrying vanA , optrA and cfr(D) in isolates associated with a multi-hospital linezolid-resistant outbreak, while short-read screening demonstrated increasing prevalence of these elements over time. These findings demonstrate the value of statewide genomic surveillance for understanding pathogen transmission, detecting emerging resistance threats and monitoring the dissemination of clinically important mobile genetic elements.