Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread

Abstract

Public health interventions to control the current epidemic of carbapenem-resistant Klebsiella pneumoniae 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 K. pneumoniae, isolated from patients 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. However, 477/682 (69.9%) of carbapenemase-positive isolates are concentrated in four clonal lineages, sequence types (ST) 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 in hospital environments correlates with the degree of resistance and that carbapenemasepositive isolates have the highest transmissibility. Indeed, we found that over half of hospitals contributing carbapenemase-positive isolates likely experienced within-hospital transmission, and inter-hospital spread is far more frequent within, rather than between, countries. Finally, 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 successful epidemic lineage, ST258/512.