Transmission analysis of carbapenem-resistant Pseudomonas aeruginosa at a tertiary care centre in Cologne (Germany) from 2015 to 2020

Background: Pseudomonas aeruginosa is a leading nosocomial pathogen and their resistance to carbapenems is either mediated via a combination of overexpressed efflux pumps and ampC with loss of porin, or through an acquired carbapenemase. While the emergence of carbapenem-resistant P. aeruginosa is well described, less is known about the different propensity of carbapenemase-producing and carbapenemase-non-producing P. aeruginosa (CPPA, nCPPA) to spread within the hospital setting, which was the aim of this study. The study was conducted in a tertiary centre in Cologne (700 beds). Methods: Identification and susceptibility testing were performed with VITEK 2 system (bioMérieux). P. aeruginosa resistant to piperacillin, ceftazidime, cefepime, imipenem, meropenem and ciprofloxacin (4MRGN according to the German classification) isolated from clinical and screening specimens from 2015 to 2020 were analysed. Isolates from several high-risk units where transmissions were previously described were included (three ICUs, one intermediate care unit). Carbapenemase tests (phenotypic test such as EDTA-CDT followed by PCR) were performed. Genotyping was carried out by whole genome sequencing (WGS, Illumina MiSeq, analysis by Ridom Seqsphere+, ad hoc cgMLST scheme); further in-silico WGS analysis were performed (Resfinder, MLST). Epidemiological and clinical data were collected from each patient.Results: Fifty-five 4MRGN-P. aeruginosa isolates were available for further analysis, of which 20 were CPPA as follows: blaVIM-1 (n=1), blaVIM-2 (n=17), blaVIM-4 (n=1), and blaNDM-1/blaGES-5 (n=1). 42 out of 55 were hospital-acquired (specimen collected more than two days after admission). cgMLST typing revealed three clusters: Cluster 1 (n=15, ST111, blaVIM-2, isolates from 2015 to 2020), cluster 2 (n=4, ST970, nCPPA) and cluster 3 (n=2, ST357, nCPPA). However, using conventional epidemiology, we were only able to confirm three independent patient-to-patient transmissions transmissions (on three different ICUs and at three different time periods) and one room-to-patient transmission in cluster 1, and three patient-to-patient transmissions (single outbreak in 2019) in cluster 2.Conclusions: These data give insight into the epidemiology of carbapenem-resistant P. aeruginosa. Transmission dynamics differed between CPPA and nCPPA: ST111 VIM-2-P. aeruginosa being a relevant driver over the whole study period of five years, and only few transmissions among nCPPA.