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 beta-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