Import of global high-risk clones is the primary driver of carbapenemase-producing Pseudomonas aeruginosa in Norway.

Abstract

Introduction. Infections by carbapenemase-producing Pseudomonas aeruginosa (CP-Pa) are concerning due to limited treatment options. The emergence of multidrug-resistant (MDR) high-risk clones is an essential driver in the global rise of CP-Pa.Hypothesis/Gap Statement. Insights into the molecular epidemiology of CP-Pa are crucial to understanding its clinical and public health impact. Despite the low incidence of infections in Norway, global spread requires an understanding of regional dissemination patterns.Aim. This study aimed to investigate the phenotypic and genotypic characteristics of CP-Pa isolates in Norway and molecular epidemiology by utilizing available metadata.Methodology. The study collection comprised all verified CP-Pa isolated in Norway from 2006 to 2022 (n=67) obtained from clinical (75%; n=50) or screening samples (22%; n=15) or had no available information (3%; n=2). Phenotypic analyses included antimicrobial susceptibility testing against clinically relevant antipseudomonal antibiotics and comparative testing for carbapenemase production using three different methods (β-CARBA, IMI/IMD gradient test and Coris O.K.N.V.I RESIST-5). Whole-genome sequencing was performed to identify virulence factors, resistance determinants and genomic relatedness.Results. The isolates were categorized as MDR (n=39) encoding Verona integron-encoded metallo-β-lactamase (VIM) (n=28), New Delhi metallo-β-lactamase (NDM) (n=6), imipenemase metallo-β-lactamase (IMP) (n=4) or Guiana extended spectrum metallo-β-lactamase (n=1) carbapenemases or extensively drug-resistant (XDR; n=28) encoding VIM (n=11), NDM (n=9) or IMP (n=8) carbapenemases. CP-Pa numbers ranged from 1 to 7 annually, peaking at 17 in 2022. Most isolates (n=64) were associated with international travel or hospitalization abroad. Phylogenetic analyses identified nine clusters of closely related genomes, with one suspected case of domestic patient-to-patient transmission. Among 21 detected sequence types, several were global high-risk clones, including ST235 (n=12), ST111 (n=9), ST773 (n=9), ST253 (n=3), ST357 (n=3), ST395 (n=3), ST823 (n=3), ST233 (n=2), ST654 (n=2), ST260 (n=1) and ST308 (n=1), covering 72% of the Norwegian isolates. ST1047 (IMP-1) and ST773 (NDM-1) were associated with Ukrainian war victims. Carbapenemase detection rates for phenotypic tests were 88% (β-CARBA), 91% (IMI/IMD) and 94% (Coris) in our collection.Conclusion. The study highlights the low incidence yet high genomic diversity of CP-Pa in Norway and the dominance of high-risk clones linked to imports, contributing to the high proportion of XDR.