Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014-2018 national laboratory surveillance

K van der Zwaluw; S Witteveen; L Wielders; M van Santen; F Landman; A de Haan; L M Schouls; T Bosch; Dutch CPE surveillance Study Group

doi:10.1016/j.cmi.2020.01.027

Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014-2018 national laboratory surveillance

Clin Microbiol Infect. 2020 Oct;26(10):1412.e7-1412.e12. doi: 10.1016/j.cmi.2020.01.027. Epub 2020 Feb 5.

Authors

K van der Zwaluw¹, S Witteveen², L Wielders², M van Santen², F Landman², A de Haan², L M Schouls², T Bosch²; Dutch CPE surveillance Study Group²

Collaborators

Dutch CPE surveillance Study Group:
J W T Cohen Stuart³, D C Melles⁴, K van Dijk⁵, C E Visser⁶, D W Notermans⁷, M L van Ogtrop⁸, B F M Werdmuller⁹, B C van Hees¹⁰, J A J W Kluytmans¹¹, W van den Bijllaardt¹¹, E M Kraan¹², M P M van der Linden¹², E E Mattsson¹³, F W Sebens¹⁴, E de Jong¹⁵, H M E Frénay¹⁶, B Maraha¹⁶, A J van Griethuysen¹⁷, G J van Asselt¹⁸, A Demeulemeester¹⁹, B B Wintermans²⁰, M van Trijp²¹, A Ott²², E Bathoorn²³, M Lokate²³, J C Sinnige²⁴, E I G B de Brauwer²⁵, F S Stals²⁵, W Silvis²⁶, L J Bakker²⁷, J W Dorigo-Zetsma²⁷, B Ridwan²⁸, K Waar²⁹, A T Bernards³⁰, S P van Mens³¹, N Roescher³², M H Nabuurs-Franssen³³, H Wertheim³⁴, T Schülin³⁵, B M W Diederen³⁶, L Bode³⁷, M van Rijn³⁸, S Dinant³⁹, O Pontesilli³⁹, P de Man⁴⁰, M A Leversteijn-van Hall⁴¹, E P M van Elzakker⁴², A E Muller⁴³, N H Renders⁴⁴, D W van Dam⁴⁵, A G M Buiting⁴⁶, A L M Vlek⁴⁷, A Reuland⁴⁸, F N J Frakking⁴⁹, I T M A Overdevest⁵⁰, R W Bosboom⁵¹, T A M Trienekens⁵², M J Bruins⁵³, M J H M Wolfhagen⁵³

Affiliations

¹ Centre for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Electronic address: Kim.van.der.Zwaluw@rivm.nl.
² Centre for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
³ Noordwest Ziekenhuisgroep, Department of Medical Microbiology, Alkmaar, the Netherlands.
⁴ Department of Medical Microbiology, Meander Medical Center Amersfoort and St. Jansdal Hospital, Harderwijk, the Netherlands.
⁵ Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Medical Microbiology and Infection Control, Amsterdam, the Netherlands.
⁶ Amsterdam UMC, Academic Medical Center, Department of Medical Microbiology, Amsterdam, the Netherlands.
⁷ Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
⁸ Onze Lieve Vrouwe Gasthuis, Department of Medical Microbiology, Amsterdam, the Netherlands.
⁹ Public Health Service, Public Health Laboratory, Amsterdam, the Netherlands.
¹⁰ Gelre Hospitals, Department of Medical Microbiology and Infection prevention, Apeldoorn, the Netherlands.
¹¹ Microvida Laboratory for Medical Microbiology, Amphia Hospital, Breda and Bravis Hospital, Bergen op Zoom and Roosendaal, the Netherlands.
¹² IJsselland Hospital, Department of Medical Microbiology, Capelle a/d IJssel, the Netherlands.
¹³ Reinier de Graaf Groep, Department of Medical Microbiology, Delft, the Netherlands.
¹⁴ Deventer Hospital, Department of Medical Microbiology, Deventer, the Netherlands.
¹⁵ Slingeland Hospital, Department of Medical Microbiology, Doetinchem, the Netherlands.
¹⁶ Albert Schweitzer Hospital, Department of Medical Microbiology, Dordrecht, the Netherlands.
¹⁷ Gelderse Vallei Hospital, Department of Medical Microbiology, Ede, the Netherlands.
¹⁸ SHL-Groep, Etten-Leur, the Netherlands; STAR Medical Diagnostic Center, Rotterdam, the Netherlands.
¹⁹ SHL-Groep, Etten-Leur, the Netherlands.
²⁰ Admiraal De Ruyter Hospital, Department of Medical Microbiology, Goes, the Netherlands.
²¹ Groene Hart Hospital, Department of Medical Microbiology and Infection Prevention, Gouda, the Netherlands.
²² Certe, Department of Medical Microbiology, Groningen, the Netherlands.
²³ University of Groningen, University Medical Center, Department of Medical Microbiology, Groningen, the Netherlands.
²⁴ Regional Laboratory of Public Health, Haarlem, the Netherlands.
²⁵ Zuyderland Medical Centre, Department of Medical Microbiology and Infection Control, Heerlen, the Netherlands.
²⁶ Laboratory of Medical Microbiology and Public Health, Hengelo, the Netherlands.
²⁷ CBSL, Tergooi Hospital, Department of Medical Microbiology, Hilversum, the Netherlands.
²⁸ Westfriesgasthuis, Department of Medical Microbiology, Hoorn, the Netherlands.
²⁹ Izore Centre for Infectious Diseases Friesland, Leeuwarden, the Netherlands.
³⁰ Leiden University Medical Center, Department of Medical Microbiology, Leiden, the Netherlands.
³¹ Maastricht University Medical Centre, Department of Medical Microbiology, Maastricht, the Netherlands.
³² St Antonius Hospital, Department of Medical Microbiology and Immunology, Nieuwegein, the Netherlands.
³³ Canisius Wilhelmina Hospital, Department of Medical Microbiology and Infectious Diseases, Nijmegen, the Netherlands.
³⁴ Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, the Netherlands.
³⁵ Laurentius Hospital, Department of Medical Microbiology, Roermond, the Netherlands.
³⁶ Department of Medical Microbiology, Bravis Hospital, Roosendaal and ZorgSaam Hospital Zeeuws-Vlaanderen, Terneuzen, the Netherlands.
³⁷ Erasmus University Medical Center, Department of Medical Microbiology, Rotterdam, the Netherlands.
³⁸ Ikazia Hospital, Department of Medical Microbiology, Rotterdam, the Netherlands.
³⁹ Maasstad Hospital, Department of Medical Microbiology, Rotterdam, the Netherlands.
⁴⁰ Sint Franciscus Gasthuis, Department of Medical Microbiology, Rotterdam, the Netherlands.
⁴¹ Haaglanden Medical Centre / Alrijne Hospital, Department of Medical Microbiology and Infection Control, 's-Gravenhage, the Netherlands.
⁴² Haga Hospital, Department of Medical Microbiology, 's-Gravenhage, the Netherlands.
⁴³ MCH Westeinde Hospital, Department of Medical Microbiology, 's-Gravenhage, the Netherlands.
⁴⁴ Jeroen Bosch Hospital, Department of Medical Microbiology and Infection Control, 's-Hertogenbosch, the Netherlands.
⁴⁵ Zuyderland Medical Centre, Department of Medical Microbiology and Infection Control, Sittard-Geleen, the Netherlands.
⁴⁶ St. Elisabeth Hospital, Department of Medical Microbiology, Tilburg, the Netherlands.
⁴⁷ Diakonessenhuis, Department of Medical Microbiology and Immunology, Utrecht, the Netherlands.
⁴⁸ Saltro Diagnostic Centre, Department of Medical Microbiology, Utrecht, the Netherlands.
⁴⁹ University Medical Center Utrecht, Department of Medical Microbiology, Utrecht, the Netherlands.
⁵⁰ PAMM, Laboratory of Medical Microbiology, Veldhoven, the Netherlands.
⁵¹ Rijnstate Hospital, Laboratory for Medical Microbiology and Immunology, Velp, the Netherlands.
⁵² VieCuri Medical Center, Department of Medical Microbiology, Venlo, the Netherlands.
⁵³ Isala Hospital, Laboratory of Medical Microbiology and Infectious Diseases, Zwolle, the Netherlands.

PMID: 32006688
DOI: 10.1016/j.cmi.2020.01.027

Abstract

Objectives: Carbapenem 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.

Methods: Meropenem 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).

Results: In 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 bla_OXA-48 being predominant (38%, 336/892), followed by bla_NDM-1 (16%, 145/892). For the first time in the Netherlands, bla_OXA-181, bla_OXA-232 and bla_VIM-4 were detected. The genetic background of K. pneumoniae and E. coli isolates was highly diverse.

Conclusions: The CPE population in the Netherlands is diverse, suggesting multiple introductions. The predominant carbapenemase alleles are bla_OXA-48 and bla_NDM-1. There was a clear association between species, carbapenemase allele and susceptibility to meropenem.

Keywords: CPE; Carbapenemase activity; Carbapenemase genes; NGS; Surveillance.

MeSH terms

Anti-Bacterial Agents / pharmacology
Bacterial Proteins / genetics*
Bacterial Proteins / metabolism
Carbapenem-Resistant Enterobacteriaceae / drug effects
Carbapenem-Resistant Enterobacteriaceae / genetics*
Carbapenem-Resistant Enterobacteriaceae / isolation & purification*
Enterobacter cloacae / drug effects
Enterobacter cloacae / genetics
Enterobacter cloacae / isolation & purification
Enterobacteriaceae Infections / drug therapy
Enterobacteriaceae Infections / epidemiology*
Enterobacteriaceae Infections / microbiology
Escherichia coli / drug effects
Escherichia coli / genetics
Escherichia coli / isolation & purification
Humans
Interspersed Repetitive Sequences / genetics
Klebsiella pneumoniae / drug effects
Klebsiella pneumoniae / genetics
Klebsiella pneumoniae / isolation & purification
Meropenem / pharmacology
Microbial Sensitivity Tests
Molecular Epidemiology
Netherlands / epidemiology
beta-Lactamases / genetics*
beta-Lactamases / metabolism

Substances

Anti-Bacterial Agents
Bacterial Proteins
beta-Lactamases
carbapenemase
Meropenem