A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing blaVIM-1and mcr-9 in the Netherlands

Antoni P. A. Hendrickx; Sylvia Debast; María Pérez-Vázquez; Annelot F. Schoffelen; Daan W. Notermans; Fabian Landman; Cornelia C. H. Wielders; Javier E. Cañada Garcia; Jacky Flipse; Angela de Haan; Sandra Witteveen; Marga van Santen-Verheuvel; Sabine C. de Greeff; Ed Kuijper; Leo M. Schouls; A. Maijer-Reuwer; M. A. Leversteijn-van Hall; J. A. J. W. Kluytmans; I. J. B. Spijkerman; K. van Dijk; T. Halaby; B. Zwart; B. M. W. Diederen; A. Voss; J. W. Dorigo-Zetsma; A. Ott; J. H. Oudbier; M. van der Vusse; A. L. M. Vlek; A. G. M. Buiting; L. Bode; S. Paltansing; A. J. van Griethuysen; M. den Reijer; M. van Trijp; E. P. M. van Elzakker; A. E. Muller; M. P. M. van der Linden; M. van Rijn; M. J. H. M. Wolfhagen; K. Waar; E. Kolwijck; W. Silvis; T. Schulin; M. Damen; S. Dinant; S. P. van Mens; D. C. Melles; J. W. T. Cohen Stuart; M. L. van Ogtrop; I. T. M. A. Overdevest; A. P. van Dam; H. Wertheim; H. M. E. Frénay; J. C. Sinnige; E. E. Mattsson; R. W. Bosboom; A. Stam; E. de Jong; N. Roescher; E. Heikens; R. Steingrover; A. Troelstra; E. Bathoorn; T. A. M. Trienekens; D. W. van Dam; E. I. G. B. de Brauwer; F. S. Stals

doi:https://doi.org/10.1093/jacamr/dlab046

A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing blaVIM-1and mcr-9 in the Netherlands

Antoni P. A. Hendrickx, Sylvia Debast, María Pérez-Vázquez, Annelot F. Schoffelen, Daan W. Notermans, Fabian Landman, Cornelia C. H. Wielders, Javier E. Cañada Garcia, Jacky Flipse, Angela de Haan, Sandra Witteveen, Marga van Santen-Verheuvel, Sabine C. de Greeff, Ed Kuijper, Leo M. Schouls, A. Maijer-Reuwer, M. A. Leversteijn-van Hall, J. A. J. W. Kluytmans, I. J. B. Spijkerman, K. van DijkT. Halaby, B. Zwart, B. M. W. Diederen, A. Voss, J. W. Dorigo-Zetsma, A. Ott, J. H. Oudbier, M. van der Vusse, A. L. M. Vlek, A. G. M. Buiting, L. Bode, S. Paltansing, A. J. van Griethuysen, M. den Reijer, M. van Trijp, E. P. M. van Elzakker, A. E. Muller, M. P. M. van der Linden, M. van Rijn, M. J. H. M. Wolfhagen, K. Waar, E. Kolwijck, W. Silvis, T. Schulin, M. Damen, S. Dinant, S. P. van Mens, D. C. Melles, J. W. T. Cohen Stuart, M. L. van Ogtrop, I. T. M. A. Overdevest, A. P. van Dam, H. Wertheim, H. M. E. Frénay, J. C. Sinnige, E. E. Mattsson, R. W. Bosboom, A. Stam, E. de Jong, N. Roescher, E. Heikens, R. Steingrover, A. Troelstra, E. Bathoorn, T. A. M. Trienekens, D. W. van Dam, E. I. G. B. de Brauwer, F. S. Stals

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Abstract

Background: Carbapenemases produced by Enterobacterales are often encoded by genes on transferable plasmids and represent a major healthcare problem, especially if the plasmids contain additional antibiotic resistance genes. As part of Dutch national surveillance, 50 medical microbiological laboratories submit their Enterobacterales isolates suspected of carbapenemase production to the National Institute for Public Health and the Environment for characterization. All isolates for which carbapenemase production is confirmed are subjected to next-generation sequencing. Objectives: To study the molecular characteristics of a genetic cluster of Enterobacter cloacae complex isolates collected in Dutch national surveillance in the period 2015-20 in the Netherlands. Methods: Short-and long-read genome sequencing was used in combination with MLST and pan-genome MLST (pgMLST) analyses. Automated antimicrobial susceptibility testing (AST), the Etest for meropenem and the broth microdilution test for colistin were performed. The carbapenem inactivation method was used to assess carbapenemase production. Results: pgMLST revealed that nine E. cloacae complex isolates from three different hospitals in the Netherlands differed by <20 alleles and grouped in a genetic cluster termed EclCluster-013. Seven isolates were submitted by one hospital in 2016-20. EclCluster-013 isolates produced carbapenemase and were from ST78, a globally disseminated lineage. EclCluster-013 isolates harboured a 316 078 bp IncH12 plasmid carrying the blaVIM-1 carbapenemase and the novel mcr-9 colistin resistance gene along with genes encoding resistance to different antibiotic classes. AST showed that EclCluster-013 isolates were MDR, but susceptible to meropenem (<2 mg/L) and colistin (<2 mg/L). Conclusions: The EclCluster-013 reported here represents an MDR E. cloacae complex ST78 strain containing an IncH12 plasmid carrying both the blaVIM-1 carbapenemase and the mcr-9 colistin resistance gene.

Original language	English
Article number	dlab046
Journal	JAC-antimicrobial resistance
Volume	3
Issue number	2
DOIs	https://doi.org/10.1093/jacamr/dlab046
Publication status	Published - 1 Jun 2021

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Hendrickx, A. P. A., Debast, S., Pérez-Vázquez, M., Schoffelen, A. F., Notermans, D. W., Landman, F., Wielders, C. C. H., Cañada Garcia, J. E., Flipse, J., de Haan, A., Witteveen, S., van Santen-Verheuvel, M., de Greeff, S. C., Kuijper, E., Schouls, L. M., Maijer-Reuwer, A., Leversteijn-van Hall, M. A., Kluytmans, J. A. J. W., Spijkerman, I. J. B., ... Stals, F. S. (2021). A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing blaVIM-1and mcr-9 in the Netherlands. JAC-antimicrobial resistance, 3(2), Article dlab046. https://doi.org/10.1093/jacamr/dlab046

@article{cf8abcb18e824df0b9a21a2e8d42234b,

title = "A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing blaVIM-1and mcr-9 in the Netherlands",

abstract = "Background: Carbapenemases produced by Enterobacterales are often encoded by genes on transferable plasmids and represent a major healthcare problem, especially if the plasmids contain additional antibiotic resistance genes. As part of Dutch national surveillance, 50 medical microbiological laboratories submit their Enterobacterales isolates suspected of carbapenemase production to the National Institute for Public Health and the Environment for characterization. All isolates for which carbapenemase production is confirmed are subjected to next-generation sequencing. Objectives: To study the molecular characteristics of a genetic cluster of Enterobacter cloacae complex isolates collected in Dutch national surveillance in the period 2015-20 in the Netherlands. Methods: Short-and long-read genome sequencing was used in combination with MLST and pan-genome MLST (pgMLST) analyses. Automated antimicrobial susceptibility testing (AST), the Etest for meropenem and the broth microdilution test for colistin were performed. The carbapenem inactivation method was used to assess carbapenemase production. Results: pgMLST revealed that nine E. cloacae complex isolates from three different hospitals in the Netherlands differed by <20 alleles and grouped in a genetic cluster termed EclCluster-013. Seven isolates were submitted by one hospital in 2016-20. EclCluster-013 isolates produced carbapenemase and were from ST78, a globally disseminated lineage. EclCluster-013 isolates harboured a 316 078 bp IncH12 plasmid carrying the blaVIM-1 carbapenemase and the novel mcr-9 colistin resistance gene along with genes encoding resistance to different antibiotic classes. AST showed that EclCluster-013 isolates were MDR, but susceptible to meropenem (<2 mg/L) and colistin (<2 mg/L). Conclusions: The EclCluster-013 reported here represents an MDR E. cloacae complex ST78 strain containing an IncH12 plasmid carrying both the blaVIM-1 carbapenemase and the mcr-9 colistin resistance gene.",

author = "Hendrickx, {Antoni P. A.} and Sylvia Debast and Mar{\'i}a P{\'e}rez-V{\'a}zquez and Schoffelen, {Annelot F.} and Notermans, {Daan W.} and Fabian Landman and Wielders, {Cornelia C. H.} and {Ca{\~n}ada Garcia}, {Javier E.} and Jacky Flipse and {de Haan}, Angela and Sandra Witteveen and {van Santen-Verheuvel}, Marga and {de Greeff}, {Sabine C.} and Ed Kuijper and Schouls, {Leo M.} and A. Maijer-Reuwer and {Leversteijn-van Hall}, {M. A.} and Kluytmans, {J. A. J. W.} and Spijkerman, {I. J. B.} and {van Dijk}, K. and T. Halaby and B. Zwart and Diederen, {B. M. W.} and A. Voss and Dorigo-Zetsma, {J. W.} and A. Ott and Oudbier, {J. H.} and {van der Vusse}, M. and Vlek, {A. L. M.} and Buiting, {A. G. M.} and L. Bode and S. Paltansing and {van Griethuysen}, {A. J.} and {den Reijer}, M. and {van Trijp}, M. and {van Elzakker}, {E. P. M.} and Muller, {A. E.} and {van der Linden}, {M. P. M.} and {van Rijn}, M. and Wolfhagen, {M. J. H. M.} and K. Waar and E. Kolwijck and W. Silvis and T. Schulin and M. Damen and S. Dinant and {van Mens}, {S. P.} and Melles, {D. C.} and {Cohen Stuart}, {J. W. T.} and {van Ogtrop}, {M. L.} and Overdevest, {I. T. M. A.} and {van Dam}, {A. P.} and H. Wertheim and Fr{\'e}nay, {H. M. E.} and Sinnige, {J. C.} and Mattsson, {E. E.} and Bosboom, {R. W.} and A. Stam and {de Jong}, E. and N. Roescher and E. Heikens and R. Steingrover and A. Troelstra and E. Bathoorn and Trienekens, {T. A. M.} and {van Dam}, {D. W.} and {de Brauwer}, {E. I. G. B.} and Stals, {F. S.}",

year = "2021",

month = jun,

day = "1",

doi = "https://doi.org/10.1093/jacamr/dlab046",

language = "English",

volume = "3",

journal = "JAC-antimicrobial resistance",

issn = "2632-1823",

publisher = "Oxford University Press",

number = "2",

}

Hendrickx, APA, Debast, S, Pérez-Vázquez, M, Schoffelen, AF, Notermans, DW, Landman, F, Wielders, CCH, Cañada Garcia, JE, Flipse, J, de Haan, A, Witteveen, S, van Santen-Verheuvel, M, de Greeff, SC, Kuijper, E, Schouls, LM, Maijer-Reuwer, A, Leversteijn-van Hall, MA, Kluytmans, JAJW, Spijkerman, IJB , van Dijk, K, Halaby, T, Zwart, B, Diederen, BMW, Voss, A, Dorigo-Zetsma, JW, Ott, A, Oudbier, JH, van der Vusse, M, Vlek, ALM, Buiting, AGM, Bode, L, Paltansing, S, van Griethuysen, AJ, den Reijer, M, van Trijp, M, van Elzakker, EPM, Muller, AE, van der Linden, MPM, van Rijn, M, Wolfhagen, MJHM, Waar, K, Kolwijck, E, Silvis, W, Schulin, T, Damen, M, Dinant, S, van Mens, SP, Melles, DC, Cohen Stuart, JWT, van Ogtrop, ML, Overdevest, ITMA, van Dam, AP, Wertheim, H, Frénay, HME, Sinnige, JC, Mattsson, EE, Bosboom, RW, Stam, A, de Jong, E, Roescher, N, Heikens, E, Steingrover, R, Troelstra, A, Bathoorn, E, Trienekens, TAM, van Dam, DW, de Brauwer, EIGB & Stals, FS 2021, 'A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing blaVIM-1and mcr-9 in the Netherlands', JAC-antimicrobial resistance, vol. 3, no. 2, dlab046. https://doi.org/10.1093/jacamr/dlab046

TY - JOUR

T1 - A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing blaVIM-1and mcr-9 in the Netherlands

AU - Hendrickx, Antoni P. A.

AU - Debast, Sylvia

AU - Pérez-Vázquez, María

AU - Schoffelen, Annelot F.

AU - Notermans, Daan W.

AU - Landman, Fabian

AU - Wielders, Cornelia C. H.

AU - Cañada Garcia, Javier E.

AU - Flipse, Jacky

AU - de Haan, Angela

AU - Witteveen, Sandra

AU - van Santen-Verheuvel, Marga

AU - de Greeff, Sabine C.

AU - Kuijper, Ed

AU - Schouls, Leo M.

AU - Maijer-Reuwer, A.

AU - Leversteijn-van Hall, M. A.

AU - Kluytmans, J. A. J. W.

AU - Spijkerman, I. J. B.

AU - van Dijk, K.

AU - Halaby, T.

AU - Zwart, B.

AU - Diederen, B. M. W.

AU - Voss, A.

AU - Dorigo-Zetsma, J. W.

AU - Ott, A.

AU - Oudbier, J. H.

AU - van der Vusse, M.

AU - Vlek, A. L. M.

AU - Buiting, A. G. M.

AU - Bode, L.

AU - Paltansing, S.

AU - van Griethuysen, A. J.

AU - den Reijer, M.

AU - van Trijp, M.

AU - van Elzakker, E. P. M.

AU - Muller, A. E.

AU - van der Linden, M. P. M.

AU - van Rijn, M.

AU - Wolfhagen, M. J. H. M.

AU - Waar, K.

AU - Kolwijck, E.

AU - Silvis, W.

AU - Schulin, T.

AU - Damen, M.

AU - Dinant, S.

AU - van Mens, S. P.

AU - Melles, D. C.

AU - Cohen Stuart, J. W. T.

AU - van Ogtrop, M. L.

AU - Overdevest, I. T. M. A.

AU - van Dam, A. P.

AU - Wertheim, H.

AU - Frénay, H. M. E.

AU - Sinnige, J. C.

AU - Mattsson, E. E.

AU - Bosboom, R. W.

AU - Stam, A.

AU - de Jong, E.

AU - Roescher, N.

AU - Heikens, E.

AU - Steingrover, R.

AU - Troelstra, A.

AU - Bathoorn, E.

AU - Trienekens, T. A. M.

AU - van Dam, D. W.

AU - de Brauwer, E. I. G. B.

AU - Stals, F. S.

PY - 2021/6/1

Y1 - 2021/6/1

N2 - Background: Carbapenemases produced by Enterobacterales are often encoded by genes on transferable plasmids and represent a major healthcare problem, especially if the plasmids contain additional antibiotic resistance genes. As part of Dutch national surveillance, 50 medical microbiological laboratories submit their Enterobacterales isolates suspected of carbapenemase production to the National Institute for Public Health and the Environment for characterization. All isolates for which carbapenemase production is confirmed are subjected to next-generation sequencing. Objectives: To study the molecular characteristics of a genetic cluster of Enterobacter cloacae complex isolates collected in Dutch national surveillance in the period 2015-20 in the Netherlands. Methods: Short-and long-read genome sequencing was used in combination with MLST and pan-genome MLST (pgMLST) analyses. Automated antimicrobial susceptibility testing (AST), the Etest for meropenem and the broth microdilution test for colistin were performed. The carbapenem inactivation method was used to assess carbapenemase production. Results: pgMLST revealed that nine E. cloacae complex isolates from three different hospitals in the Netherlands differed by <20 alleles and grouped in a genetic cluster termed EclCluster-013. Seven isolates were submitted by one hospital in 2016-20. EclCluster-013 isolates produced carbapenemase and were from ST78, a globally disseminated lineage. EclCluster-013 isolates harboured a 316 078 bp IncH12 plasmid carrying the blaVIM-1 carbapenemase and the novel mcr-9 colistin resistance gene along with genes encoding resistance to different antibiotic classes. AST showed that EclCluster-013 isolates were MDR, but susceptible to meropenem (<2 mg/L) and colistin (<2 mg/L). Conclusions: The EclCluster-013 reported here represents an MDR E. cloacae complex ST78 strain containing an IncH12 plasmid carrying both the blaVIM-1 carbapenemase and the mcr-9 colistin resistance gene.

AB - Background: Carbapenemases produced by Enterobacterales are often encoded by genes on transferable plasmids and represent a major healthcare problem, especially if the plasmids contain additional antibiotic resistance genes. As part of Dutch national surveillance, 50 medical microbiological laboratories submit their Enterobacterales isolates suspected of carbapenemase production to the National Institute for Public Health and the Environment for characterization. All isolates for which carbapenemase production is confirmed are subjected to next-generation sequencing. Objectives: To study the molecular characteristics of a genetic cluster of Enterobacter cloacae complex isolates collected in Dutch national surveillance in the period 2015-20 in the Netherlands. Methods: Short-and long-read genome sequencing was used in combination with MLST and pan-genome MLST (pgMLST) analyses. Automated antimicrobial susceptibility testing (AST), the Etest for meropenem and the broth microdilution test for colistin were performed. The carbapenem inactivation method was used to assess carbapenemase production. Results: pgMLST revealed that nine E. cloacae complex isolates from three different hospitals in the Netherlands differed by <20 alleles and grouped in a genetic cluster termed EclCluster-013. Seven isolates were submitted by one hospital in 2016-20. EclCluster-013 isolates produced carbapenemase and were from ST78, a globally disseminated lineage. EclCluster-013 isolates harboured a 316 078 bp IncH12 plasmid carrying the blaVIM-1 carbapenemase and the novel mcr-9 colistin resistance gene along with genes encoding resistance to different antibiotic classes. AST showed that EclCluster-013 isolates were MDR, but susceptible to meropenem (<2 mg/L) and colistin (<2 mg/L). Conclusions: The EclCluster-013 reported here represents an MDR E. cloacae complex ST78 strain containing an IncH12 plasmid carrying both the blaVIM-1 carbapenemase and the mcr-9 colistin resistance gene.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85130268744&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/34223115

U2 - https://doi.org/10.1093/jacamr/dlab046

DO - https://doi.org/10.1093/jacamr/dlab046

M3 - Article

C2 - 34223115

SN - 2632-1823

VL - 3

JO - JAC-antimicrobial resistance

JF - JAC-antimicrobial resistance

IS - 2

M1 - dlab046

ER -

A genetic cluster of MDR Enterobacter cloacae complex ST78 harbouring a plasmid containing blaVIM-1and mcr-9 in the Netherlands

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