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

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) are of particular concern due to the spread of antibiotic resistance genes associated with mobile genetic elements. In this study, we collected 687 carbapenem-resistant strains recovered among clinical samples from 41 hospitals in nine Southern European countries (2016-2018). We identified 11 major clonal lineages, with most isolates belonging to the high-risk clones ST258/512, ST101, ST11, and ST307. bla_KPC-like was the most prevalent carbapenemase-encoding gene (46%), with bla_OXA-48 present in 39% of isolates. Through the combination and comparison of this EURECA collection with the previous EuSCAPE collection (2013-2014), we investigated the spread of high-risk clones circulating in Europe exhibiting regional differences. We particularly found bla_KPC-like ST258/512 in Greece, Italy, and Spain, bla_OXA-48 ST101 in Serbia and Romania, bla_NDM ST11 in Greece, and bla_OXA-48-like ST14 in Türkiye. Genomic surveillance across Europe thus provides crucial insights for local risk mapping and informs necessary adaptions for implementation of control strategies.

Fig. 1. Phylogenetic overview tree of the complete CRKP EURECA collection.

This phylogenetic tree contains 683 Klebsiella pneumoniae sensu stricto carbapenem resistant isolates collected as part of the EURECA study. The inner ring shows sequence type, and the different colors of the outer ring depict the carbapenemase genes. Main Sequence types with more than five isolates have been labeled.

Fig. 2. Comparison of EuSCAPE and EURECA surveys of carbapenem resistant K.pneumoniae.

a Proportion of the EuSCAPE carbapenem susceptible (CSKP) clonal lineages. b and c Clonal lineages of CRKP isolates of EuSCAPE and EURECA, respectively. d European countries, which participated in EuSCAPE (green), EURECA (blue), and the overlap of both surveys (purple). Map created with mapchart.net and included under CC BY-SA 4.0 licence. e and f Distribution of carbapenem resistance genes in EuSCAPE and EURECA, respectively.

Fig. 3. Global spread of the epidemic ST258/512.

A phylogenetic tree of 856 isolates of ST258, ST512 and single locus variants with 204 isolates from EURECA, 236 isolates submitted to EuSCAPE, and 415 isolates with publicly available sequence data. Reference genome: 30660/NJST258 (CP006923). Tree tip colors correspond to country. Columns indicate: Project, (1) country, (2) ST, (3) and KPC-variant. (4) For further metadata and interactive exploration, follow this Microreact link: https://microreact.org/project/gUrL4jULY1JEPNExrFK4zH-globalcollectionclonallineage258512.

Fig. 4. Phylogenetic analysis of ST307.

Combined analysis of 117 isolates from EuSCAPE and EURECA. Reference genome CPKp1825 (WMHT01). Columns present the information about: 1 – Project, 2 – single locus variants, 3 – Country, 4 – Different hospitals (shades for each country), 5 – Carbapenemase genes. Putative outbreaks are highlighted with orange branches, and clades of interest discussed in the text are shaded with boxes (pink for Italy and purple for Spain).

Fig. 5. Phylogenetic analysis of ST11.

a Combined analysis of 329 isolates from EuSCAPE and EURECA. Reference genome F64 (VILG01). Inner ring: project, (1) middle ring: geographic origin, (2) outer ring: carbapememase genes. (3) b Phylogenetic relationship between isolates ST11 from Serbia only. Columns display the information about project, (1) different colors representing different hospitals in Serbia, (4) SNP distance, (5) and carbapenemase genes (3).