Article
Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread: Inference from a continent-wide population analysis
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Published: | April 25, 2019 |
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Over the last decade, carbapenemase-resistant Enterobacterales (Enterobacteriaceae) most notable Klebsiella pneumoniae contributed the fastest increasing burden of disease in terms of numbers of infections and numbers of deaths across Europe. Public health interventions to control this current epidemic are reliant upon a comprehensive understanding of their emergence and spread over a wide range of geographical scales. We analysed the genome sequences and epidemiological data of >1700 Klebsiella pneumoniae, isolated from patients treated in 244 hospitals in 32 countries, during the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE). We demonstrate that carbapenemase acquisition is the main cause of carbapenem resistance and has occurred across diverse phylogenetic backgrounds including 69 sequence types (ST) of K. pneumoniae sensu stricto. However, 477/682 (69.9%) of the carbapenemase-positive isolates are concentrated in just four major clonal lineages, STs 11, 15, 101, 258/512, and their derivatives. Combined analysis of the genetic and geographic distances between isolates with different beta-lactam resistance determinants suggests that the propensity of K. pneumoniae to spread within and between hospitals correlates with the degree of resistance and that carbapenemase-positive isolates have the highest transmissibility. More than half of sampled hospitals that contributed carbapenemase-positive isolates likely experienced within-hospital transmission, and inter-hospital spread is far more frequent within a single country than across national borders. We propose a value of 21 for the number of single nucleotide polymorphisms (SNPs) that optimises discrimination of hospital clusters, and detail the international spread of the most successful epidemic lineage, ST258/512. Our analyses provide population-level evidence that the epidemic of carbapenemase-producing K. pneumoniae in Europe is driven by nosocomial spread, and that natural selection in environments with dense antibiotic use favours the transmission of few hospital-adapted clones.