Public health interventions to control the current epidemic of carbapenem-resistant Klebsiella pneumoniae rely on a comprehensive understanding of its emergence and spread over a wide range of geographical scales. We analysed the genome sequences and epidemiological data of >1,700 K. pneumoniae samples isolated from patients in 244 hospitals in 32 countries during the European Survey of Carbapenemase-Producing Enterobacteriaceae. We demonstrate that carbapenemase acquisition is the main cause of carbapenem resistance and that it occurred across diverse phylogenetic backgrounds. However, 477 of 682 (69.9%) carbapenemase-positive isolates are concentrated in four clonal lineages, sequence types 11, 15, 101, 258/512 and their derivatives. Combined analysis of the genetic and geographic distances between isolates with different β-lactam resistance determinants suggests that the propensity of K. pneumoniae to spread in hospital environments correlates with the degree of resistance and that carbapenemase-positive isolates have the highest transmissibility. Indeed, we found that over half of the hospitals that contributed carbapenemase-positive isolates probably experienced within-hospital transmission, and interhospital spread is far more frequent within, rather than between, countries. Finally, we propose a value of 21 for the number of single nucleotide polymorphisms that optimizes the discrimination of hospital clusters and detail the international spread of the successful epidemic lineage, ST258/512.
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All raw and assembled Illumina sequence data are available from the European Nucleotide Archive under the study accession no. PRJEB10018/ERP011196. Individual accession numbers for raw sequence data and de novo assemblies are also available in Supplementary Table 4. Phylogenetic analysis of the 1,717 K. pneumoniae isolates (EuSCAPE only) and the ST258/512 isolates (EuSCAPE and public data) together with all metadata and links to raw sequence data are available at the project URLs https://microreact.org/project/EuSCAPE_Kp and https://microreact.org/project/EuSCAPE_ST258 within Microreact (ref. 51). Phylogenetic analyses and the metadata of the isolates are also available separately for each of the contributing countries in Microreact (see Supplementary Table 7 for project URLs).
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We thank the Pathogen Informatics Group and Core Sequencing Facility at the Wellcome Sanger Institute for their contributions to the study. We also thank F. Bosma and M. Zigterman from the Medical Microbiology and Infection Prevention Department of the University Medical Center Groningen for their support in assembling the isolate collection. This work was funded by The Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Wellcome (grant nos. 098051 and 099202) and the NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance (NIHR 16/136/111). The EuSCAPE project was funded by ECDC through a specific framework contract (ECDC/2012/055) following an open call for tender (OJ/25/04/2012-PROC/2012/036). This work was carried out on behalf of the ESCMID Study Group for Epidemiological Markers (ESGEM); the full list of members is provided in the Supplementary Information.
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Figs. 1–3, Supplementary Table 1, Supplementary Table 5, Supplementary Table 7 and Supplementary Note.
Detailed QC results for all sequenced isolates submitted as K. pneumoniae.
Identification of best-matching taxa to the individual assembly contigs of all sequenced isolates using Mash.
Epidemiological and genotyping data for 1,717 K. pneumoniae isolates that passed sequencing QC filters.
Epidemiological and genotyping data and publication sources of 651 isolates used in the ST258/512 phylogenetic analysis.