Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014–2018 national laboratory surveillance
Kim van der Zwaluw, Sandra Witteveen, L. Wielders, Marga van Santen, Fabian Landman, Angela de Haan, Leo M. Schouls, Thijs Bosch, J. W. T. Cohen Stuart, Damian C. Melles∗, Karin van Dijk, Caroline E. Visser, Daan W. Notermans, M L van Ogtrop, B. F. M. Werdmuller, B.C. van Hees, Jan Kluytmans, Wouter van den Bijllaardt, E.M. Kraan, M. P. M. van der Linden, Eva Mattsson, F.W. Sebens, E.M.G.J. de Jong, H. M. E. Frénay, B. Maraha, A. J. van Griethuysen, G. J. van Asselt, A. A. Demeulemeester, B.B. Wintermans, M. van Trijp, Alewijn Ott, Erik Bathoorn, Mariëtte Lokate, J. C. Sinnige, E. I. G. B. de Brauwer, F S Stals, W. Silvis, Lytske Bakker, J W Dorigo-Zetsma, B U Ridwan, K. Waar, A.T. Bernards, S. P. van Mens, Nienke Roescher, Marrigje H. Nabuurs-Franssen, Heiman Wertheim, T. Schülin, B. M. W. Diederen, L. Bode, M. van Rijn, S. Dinant, Oscar Pontesilli, Petr Man, Michael Hall, E.P.M. van Elzakker, Anouk E. Muller, Nicole H. M. Renders, D. W. van Dam, A. G. M. Buiting, A. L. M. Vlek, Ascelijn E. Reuland, F.N.J. Frakking, I. T. M. A. Overdevest, Ron Bosboom, T. A. M. Trienekens, Marjan J. Bruins, M. J. H. M. Wolfhagen
Abstract
ObjectivesCarbapenem resistance mediated by mobile genetic elements has emerged worldwide and has become a major public health threat. To gain insight into the molecular epidemiology of carbapenem resistance in The Netherlands, Dutch medical microbiology laboratories are requested to submit suspected carbapenemase-producing Enterobacterales (CPE) to the National Institute for Public Health and the Environment as part of a national surveillance system.MethodsMeropenem MICs and species identification were confirmed by E-test and MALDI-TOF and carbapenemase production was assessed by the Carbapenem Inactivation Method. Of all submitted CPE, one species/carbapenemase gene combination per person per year was subjected to next-generation sequencing (NGS).ResultsIn total, 1838 unique isolates were received between 2014 and 2018, of which 892 were unique CPE isolates with NGS data available. The predominant CPE species were Klebsiella pneumoniae (n = 388, 43%), Escherichia coli (n = 264, 30%) and Enterobacter cloacae complex (n = 116, 13%). Various carbapenemase alleles of the same carbapenemase gene resulted in different susceptibilities to meropenem and this effect varied between species. Analyses of NGS data showed variation of prevalence of carbapenemase alleles over time with blaOXA-48 being predominant (38%, 336/892), followed by blaNDM-1 (16%, 145/892). For the first time in the Netherlands, blaOXA-181, blaOXA-232 and blaVIM-4 were detected. The genetic background of K. pneumoniae and E. coli isolates was highly diverse.ConclusionsThe CPE population in the Netherlands is diverse, suggesting multiple introductions. The predominant carbapenemase alleles are blaOXA-48 and blaNDM-1. There was a clear association between species, carbapenemase allele and susceptibility to meropenem.