Investigation of VIM-1-producing Enterobacter spp. across Switzerland: clonal dissemination and plasmid transmission

Carbapenemase-producing Enterobacterales (CPE) are a major public health concern. Within the Enterobacter cloacae complex (ECC), the bla_VIM-1 carbapenemase gene is frequently plasmid-borne, enabling inter-clonal and inter-species spread that complicates the detection and control of carbapenemase dissemination. We investigated an increase in VIM-1-producing Enterobacter spp. reported to the Swiss National Reference Center for Emerging Antibiotic Resistance (NARA) between 2022 and 2024 using high-resolution genomic methods. Between January 2022 and October 2024, bla_VIM-1-positive Enterobacter spp. isolates from 39 patients, plus additional contemporary bla_VIM-1-positive Enterobacterales, were analyzed. Whole-genome sequencing (Illumina) was performed for all isolates, with long-read sequencing (Oxford Nanopore Technologies) for 12 selected isolates. Species identification, genomic relatedness by MLST and cgMLST, and fine-scale plasmid characterization and comparison were performed. Most isolates were Enterobacter hormaechei (n = 37), alongside Enterobacter kobei (n = 1) and Enterobacter ludwigii (n = 1), distributed across 13 sequence types, excluding purely clonal dissemination. Hybrid assemblies showed bla_VIM-1 located on several plasmid types. IncHI2 plasmids of 249-343 kb carrying additional antimicrobial resistance promoting genes including mcr-9 predominated, spanning multiple ECC lineages and also present in two other species. Conjugation of these was confirmed experimentally, and within-host plasmid variation was observed. No further cases occurred after October 2024. We describe a multiclonal spread of bla_VIM-1 Enterobacterales in Switzerland, mediated by IncHI2 plasmids. These findings highlight the need for plasmid-focused genomic surveillance to complement clonal typing in CPE outbreak investigations.