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

David, S.; Reuter, S.; Harris, S. R.; Glasner, C.; Feltwell, T.; Argimon, S.; Abudahab, K.; Goater, R.; Giani, T.; Errico, G.; Aspbury, M.; Sjunnebo, S.; Koraqi, A.; Lacej, D.; Apfalter, P.; Hartl, R.; Glupczynski, Y.; Huang, T. -D.; Strateva, T.; Marteva-Proevska, Y.; Andrasevic, A. T.; Butic, I.; Pieridou-Bagatzouni, D.; Maikanti-Charalampous, P.; Hrabak, J.; Zemlickova, H.; Hammerum, A.; Jakobsen, L.; Ivanova, M.; Pavelkovich, A.; Jalava, J.; Osterblad, M.; Dortet, L.; Vaux, S.; Kaase, M.; Gatermann, S. G.; Vatopoulos, A.; Tryfinopoulou, K.; Toth, A.; Janvari, L.; Boo, T. W.; Mcgrath, E.; Carmeli, Y.; Adler, A.; Pantosti, A.; Monaco, M.; Raka, L.; Kurti, A.; Balode, A.; Saule, M.; Miciuleviciene, J.; Mierauskaite, A.; Perrin-Weniger, M.; Reichert, P.; Nestorova, N.; Debattista, S.; Mijovic, G.; Lopicic, M.; Samuelsen, O.; Haldorsen, B.; Zabicka, D.; Literacka, E.; Canica, M.; Manageiro, V.; Kaftandzieva, A.; Trajkovska-Dokic, E.; Damian, M.; Lixandru, B.; Jelesic, Z.; Trudic, A.; Niks, M.; Schreterova, E.; Pirs, M.; Cerar, T.; Oteo, J.; Aracil, B.; Giske, C.; Sjostrom, K.; Gur, D.; Cakar, A.; Woodford, N.; Hopkins, K.; Wiuff, C.; Brown, D. J.; Feil, E. J.; Rossolini, G. M.; Aanensen, D. M.; Grundmann, H.

doi:10.1038/s41564-019-0492-8

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.

Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread / David S.; Reuter S.; Harris S.R.; Glasner C.; Feltwell T.; Argimon S.; Abudahab K.; Goater R.; Giani T.; Errico G.; Aspbury M.; Sjunnebo S.; Koraqi A.; Lacej D.; Apfalter P.; Hartl R.; Glupczynski Y.; Huang T.-D.; Strateva T.; Marteva-Proevska Y.; Andrasevic A.T.; Butic I.; Pieridou-Bagatzouni D.; Maikanti-Charalampous P.; Hrabak J.; Zemlickova H.; Hammerum A.; Jakobsen L.; Ivanova M.; Pavelkovich A.; Jalava J.; Osterblad M.; Dortet L.; Vaux S.; Kaase M.; Gatermann S.G.; Vatopoulos A.; Tryfinopoulou K.; Toth A.; Janvari L.; Boo T.W.; McGrath E.; Carmeli Y.; Adler A.; Pantosti A.; Monaco M.; Raka L.; Kurti A.; Balode A.; Saule M.; Miciuleviciene J.; Mierauskaite A.; Perrin-Weniger M.; Reichert P.; Nestorova N.; Debattista S.; Mijovic G.; Lopicic M.; Samuelsen O.; Haldorsen B.; Zabicka D.; Literacka E.; Canica M.; Manageiro V.; Kaftandzieva A.; Trajkovska-Dokic E.; Damian M.; Lixandru B.; Jelesic Z.; Trudic A.; Niks M.; Schreterova E.; Pirs M.; Cerar T.; Oteo J.; Aracil B.; Giske C.; Sjostrom K.; Gur D.; Cakar A.; Woodford N.; Hopkins K.; Wiuff C.; Brown D.J.; Feil E.J.; Rossolini G.M.; Aanensen D.M.; Grundmann H.. - In: NATURE MICROBIOLOGY. - ISSN 2058-5276. - ELETTRONICO. - 4:(2019), pp. 1919-1929. [10.1038/s41564-019-0492-8]