International and regional spread of carbapenem-resistant Klebsiella pneumoniae in Europe

Klebsiella pneumoniae, an opportunistic pathogen able to cause hospital- and community-acquired infections, is of particular concern due to the active spread of antibiotic resistance genes associated with mobile genetic elements such as plasmids and transposons. Carbapenem-resistant K. pneumoniae (CRKP) exhibit a higher mortality rate than carbapenem-susceptible K. pneumoniae infections. In this COMBACTE-EURECA study, we present genomic data of 687 carbapenem-resistant strains recovered among clinical samples from 41 hospitals in nine Southern European countries (2016-2018) and compared these with the previous EuSCAPE collection (2013-2014). All isolates were resistant (EUCAST criteria) to at least one carbapenem antibiotic. We identified 11 clonal complexes (CCs), with most isolates belonging to the high-risk clones CC258, CC101, CC11, and CC307. blaKPC-like was the most prevalent carbapenemase-encoding gene (45%), along with the dominance of the CC258 lineage. Equally, blaOXA-48 had a wide-ranging spread (39%), and blaNDM was present in half of the ST11 isolates representing a particular lineage circulating in Greece. Two carbapenemase genes were found in 38 isolates (5.5%). Through the combination of both EURECA and EuSCAPE collections, we elucidated the evolution of K. pneumoniae high-risk clones circulating in Europe. Dominating clones and their associated carbapenemase genes exhibit relevant regional differences, namely CC258 in Greece, Italy, and Spain, CC101 present in Serbia and Romania and CC14 in Turkiye. Due to the wide expansion of CRKP, genomic surveillance across Europe with projects such as EURECA provides crucial insights for risk mapping at geo-temporal scales and informs necessary adaptions to the local settings for implementation of control strategies.