Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission

Jessica Martin; Hang T T Phan; Jacqueline Findlay; Nicole Stoesser; Louise Pankhurst; Indre Navickaite; Nicola De Maio; David W Eyre; Giles Toogood; Nicolas M Orsi; Andrew Kirby; Nicola Young; Jane F Turton; Robert L R Hill; Katie L Hopkins; Neil Woodford; Tim E A Peto; A Sarah Walker; Derrick W Crook; Mark H Wilcox

doi:10.1093/jac/dkx264

Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission

Jessica Martin, Hang T T Phan, Jacqueline Findlay, Nicole Stoesser, Louise Pankhurst, Indre Navickaite, Nicola De Maio, David W Eyre, Giles Toogood, Nicolas M Orsi, Andrew Kirby, Nicola Young, Jane F Turton, Robert L R Hill, Katie L Hopkins, Neil Woodford, Tim E A Peto, A Sarah Walker, Derrick W Crook, Mark H Wilcox

School of Cellular and Molecular Medicine

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC -Kpn ), are an increasing threat to patient safety.

Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak.

Materials and methods: Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013-14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn 4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI.

Results: Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC -Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn 4401 a), except one KPC -Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC -Kpn (ST491) with Tn 4401 a-carrying pKpQIL-D2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC -Kpn (ST14,ST661) including clonal spread of KPC- Kpn (ST661) from a symptomatic case to nine ward contacts.

Conclusions: WGS of outbreak KPC isolates demonstrated bla KPC dissemination via horizontal transposition (Tn 4401 a), plasmid spread (pKpQIL-D2) and clonal spread ( K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of bla KPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts.

Original language	English
Pages (from-to)	3025-3034
Journal	Journal of Antimicrobial Chemotherapy
Volume	72
Issue number	11
DOIs	https://doi.org/10.1093/jac/dkx264
Publication status	Published - 7 Aug 2017

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Journal Article

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Martin, J., Phan, H. T. T., Findlay, J., Stoesser, N., Pankhurst, L., Navickaite, I., De Maio, N., Eyre, D. W., Toogood, G., Orsi, N. M., Kirby, A., Young, N., Turton, J. F., Hill, R. L. R., Hopkins, K. L., Woodford, N., Peto, T. E. A., Walker, A. S., Crook, D. W., & Wilcox, M. H. (2017). Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission. Journal of Antimicrobial Chemotherapy, 72(11), 3025-3034. https://doi.org/10.1093/jac/dkx264

@article{9df3b7807a4d4dc09f9dcaba084e40a4,

title = "Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission",

abstract = "Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC -Kpn ), are an increasing threat to patient safety.Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak.Materials and methods: Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013-14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn 4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI.Results: Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC -Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn 4401 a), except one KPC -Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC -Kpn (ST491) with Tn 4401 a-carrying pKpQIL-D2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC -Kpn (ST14,ST661) including clonal spread of KPC- Kpn (ST661) from a symptomatic case to nine ward contacts.Conclusions: WGS of outbreak KPC isolates demonstrated bla KPC dissemination via horizontal transposition (Tn 4401 a), plasmid spread (pKpQIL-D2) and clonal spread ( K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of bla KPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts.",

keywords = "Journal Article",

author = "Jessica Martin and Phan, {Hang T T} and Jacqueline Findlay and Nicole Stoesser and Louise Pankhurst and Indre Navickaite and {De Maio}, Nicola and Eyre, {David W} and Giles Toogood and Orsi, {Nicolas M} and Andrew Kirby and Nicola Young and Turton, {Jane F} and Hill, {Robert L R} and Hopkins, {Katie L} and Neil Woodford and Peto, {Tim E A} and Walker, {A Sarah} and Crook, {Derrick W} and Wilcox, {Mark H}",

year = "2017",

month = aug,

day = "7",

doi = "10.1093/jac/dkx264",

language = "English",

volume = "72",

pages = "3025--3034",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "11",

}

Martin, J, Phan, HTT, Findlay, J, Stoesser, N, Pankhurst, L, Navickaite, I, De Maio, N, Eyre, DW, Toogood, G, Orsi, NM, Kirby, A, Young, N, Turton, JF, Hill, RLR, Hopkins, KL, Woodford, N, Peto, TEA, Walker, AS, Crook, DW & Wilcox, MH 2017, 'Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission', Journal of Antimicrobial Chemotherapy, vol. 72, no. 11, pp. 3025-3034. https://doi.org/10.1093/jac/dkx264

Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission. / Martin, Jessica; Phan, Hang T T; Findlay, Jacqueline et al.
In: Journal of Antimicrobial Chemotherapy, Vol. 72, No. 11, 07.08.2017, p. 3025-3034.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak

T2 - long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission

AU - Martin, Jessica

AU - Phan, Hang T T

AU - Findlay, Jacqueline

AU - Stoesser, Nicole

AU - Pankhurst, Louise

AU - Navickaite, Indre

AU - De Maio, Nicola

AU - Eyre, David W

AU - Toogood, Giles

AU - Orsi, Nicolas M

AU - Kirby, Andrew

AU - Young, Nicola

AU - Turton, Jane F

AU - Hill, Robert L R

AU - Hopkins, Katie L

AU - Woodford, Neil

AU - Peto, Tim E A

AU - Walker, A Sarah

AU - Crook, Derrick W

AU - Wilcox, Mark H

PY - 2017/8/7

Y1 - 2017/8/7

N2 - Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC -Kpn ), are an increasing threat to patient safety.Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak.Materials and methods: Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013-14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn 4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI.Results: Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC -Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn 4401 a), except one KPC -Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC -Kpn (ST491) with Tn 4401 a-carrying pKpQIL-D2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC -Kpn (ST14,ST661) including clonal spread of KPC- Kpn (ST661) from a symptomatic case to nine ward contacts.Conclusions: WGS of outbreak KPC isolates demonstrated bla KPC dissemination via horizontal transposition (Tn 4401 a), plasmid spread (pKpQIL-D2) and clonal spread ( K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of bla KPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts.

AB - Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC -Kpn ), are an increasing threat to patient safety.Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak.Materials and methods: Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013-14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn 4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI.Results: Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC -Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn 4401 a), except one KPC -Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC -Kpn (ST491) with Tn 4401 a-carrying pKpQIL-D2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC -Kpn (ST14,ST661) including clonal spread of KPC- Kpn (ST661) from a symptomatic case to nine ward contacts.Conclusions: WGS of outbreak KPC isolates demonstrated bla KPC dissemination via horizontal transposition (Tn 4401 a), plasmid spread (pKpQIL-D2) and clonal spread ( K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of bla KPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts.

KW - Journal Article

U2 - 10.1093/jac/dkx264

DO - 10.1093/jac/dkx264

M3 - Article (Academic Journal)

C2 - 28961793

SN - 0305-7453

VL - 72

SP - 3025

EP - 3034

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 11

ER -

Martin J, Phan HTT, Findlay J, Stoesser N, Pankhurst L, Navickaite I et al. Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission. Journal of Antimicrobial Chemotherapy. 2017 Aug 7;72(11):3025-3034. doi: 10.1093/jac/dkx264