Investigation of VIM-1-producing <i>Enterobacter</i> spp. across Switzerland: clonal dissemination and plasmid transmission
Abstract
Carbapenemase-producing Enterobacterales (CPE) are a major public health concern. Within the <i>Enterobacter cloacae</i> complex (ECC), the <i>bla</i><sub>VIM-1</sub> 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 <i>Enterobacter</i> 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, <i>bla</i><sub>VIM-1</sub>-positive <i>Enterobacter</i> spp. isolates from 39 patients, plus additional contemporary <i>bla</i><sub>VIM-1</sub>-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 <i>Enterobacter hormaechei</i> (<i>n</i> = 37), alongside <i>Enterobacter kobei</i> (<i>n</i> = 1) and <i>Enterobacter ludwigii</i> (<i>n</i> = 1), distributed across 13 sequence types, excluding purely clonal dissemination. Hybrid assemblies showed <i>bla</i><sub>VIM-1</sub> located on several plasmid types. IncHI2 plasmids of 249-343 kb carrying additional antimicrobial resistance promoting genes including <i>mcr-9</i> 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 <i>bla</i><sub>VIM-1</sub> 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.