An outbreak of VIM-1-producing Enterobacterales in a tertiary care centre in Germany

Multispecies plasmid-driven outbreaks of carbapenemase-producing Enterobacterales (CPE) are reported worldwide and difficult to detect and thus to address in infection prevention and control (IPC). To better understand the local epidemiology, we analysed clinical and environmental VIM-1-CPE from a medical department of a tertiary care centre in Cologne (Germany) detected over a period of ten years (2011 to 2020). Patients hospitalised on three wards (general ward, ICU and intermediate care unit (ImCU)) were included. VIM-1-producing Enterobacter cloacae complex and Citrobacter freundii isolates from patients (n=22) and the clinical environment (n=14, water drains) were included and subjected to short- and long-read WGS (Illumina MiSeq and Oxford Nanopore). WGS data was subsequently analysed (cgMLST by Seqsphere based on an ad-hoc scheme of 3,643 targets, ResFinder, MLST, Jspecies, Unicylcer, Bandage, PlasmIDent, PlasmidFinder) and the results were matched with clinical and epidemiological data. Fifteen E. hormaechei spp. steigerwaltii (EHS; ST45, ST91), 12 spp. hoffmannii (EHH; ST78, ST102), four spp. xiangfangensis (EHX; ST105, ST171), one E. asburiae (ST484) and four C. freundii (ST18, ST256, ST540, ST972) isolates were detected. cgMLST analysis led to the identification of three clonal outbreaks with different localisation of the blaVIM-1 gene: cluster 1 (8 patients, ICU, EHS ST91, IncN-plasmid_1, 2015-2020) and cluster 2 (2 patients, ImCU, EHH ST78, non-Inc-type-plasmid_2, 2017-2019) and cluster 3 (3 patients, ICU, EHS ST45, IncFIB-plasmid_3 and chromosomal localisation, 2017-2020). All three outbreaks displayed probable patient-to-patient and environment-to-patient transmissions. Overall, the blaVIM-1 gene was found on five different plasmids, each one linked to a different integron array. Moreover, plasmid_1 and plamid_2 as well as another one (IncA-plasmid_4) were found with nearly identical scaffolds in different species of sporadic cases of hospital-acquired CPE and also in the environment. The data show that both clonal spread and horizontal gene transfer are drivers of dissemination of the blaVIM-1 gene. The outbreaks and also sporadic cases of CPE are probably sustained by biofilms from the sewage system (sinks and drains). This highlights the importance of targeted IPC measures - technical, chemical and educational - addressing these sources to ensure safe patient care.