A large, refractory nosocomial outbreak of klebsiella pneumoniae carbapenemase-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control

the TRACE Investigators’ Group

doi:10.1128/AAC.01689-18

A large, refractory nosocomial outbreak of klebsiella pneumoniae carbapenemase-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control

the TRACE Investigators’ Group

Research output: Contribution to journal › Article › peer-review

96 Citations (Scopus)

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) represent a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly being highlighted as important potential reservoirs. We investigated a large Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli outbreak and wider CRE incidence trends in the Central Manchester University Hospital NHS Foundation Trust (CMFT) (United Kingdom) over 8 years, to determine the impact of infection prevention and control measures. Bacteriology and patient administration data (2009 to 2017) were linked, and a subset of CMFT or regional hospital KPC-producing E. coli isolates (n 268) were sequenced. Control interventions followed international guidelines and included cohorting, rectal screening (n 184,539 screens), environmental sampling, enhanced cleaning, and ward closure and plumbing replacement. Segmented regression of time trends for CRE detections was used to evaluate the impact of interventions on CRE incidence. Genomic analysis (n 268 isolates) identified the spread of a KPC-producing E. coli outbreak clone (strain A, sequence type 216 [ST216]; n 125) among patients and in the environment, particularly on 2 cardiac wards (wards 3 and 4), despite control measures. ST216 strain A had caused an antecedent outbreak and shared its KPC plasmids with other E. coli lineages and Enterobacteriaceae species. CRE acquisition incidence declined after closure of wards 3 and 4 and plumbing replacement, suggesting an environmental contribution. However, ward 3/ward 4 wastewater sites were rapidly recolonized with CRE and patient CRE acquisitions recurred, albeit at lower rates. Patient relocation and plumbing replacement were associated with control of a clonal KPC-producing E. coli outbreak; however, environmental contamination with CRE and patient CRE acquisitions recurred rapidly following this intervention. The large numbers of cases and the persistence of bla_KPC in E. coli, including pathogenic lineages, are of concern.

Original language	English
Article number	e01689-18
Journal	Antimicrobial Agents and Chemotherapy
Volume	62
Issue number	12
DOIs	https://doi.org/10.1128/AAC.01689-18
Publication status	Published - Dec 2018

Bibliographical note

Funding Information:
We are grateful for and acknowledge the contributions of the clinical and support staff working in the MHC, CMFT; the microbiology laboratory staff and infection control teams at CMFT; the staff of the Manchester Medical Microbiology Partnership; and the research laboratory (in particular, Ali Vaughan) and informatics and project management teams working as part of the Modernising Medical Microbiology consortium (Oxford). We thank Jeff Scott, Ashley Sharp, and Theresa Shryane (Public Health England [PHE] North West) and Suzan Trienekens (Field Epidemiology Service, PHE) for data collection and Karen Mathieson (CMFT), Jane Turton, and Claire Perry (PHE) for outbreak investigation and support. We thank the Health Protection Research Unit Steering Group for review of the draft manuscript. This work was supported by the National Institute for Health Research, Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford University, in partnership with PHE (grant HPRU-2012-10041). The report presents independent research funded by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, or PHE. N.S. is funded by a PHE-University of Oxford Clinical Lectureship. Contemporaneous outbreak investigation by CMFT and PHE was undertaken as part of routine activity.

Funding Information:
We are grateful for and acknowledge the contributions of the clinical and support staff working in the MHC, CMFT; the microbiology laboratory staff and infection control teams at CMFT; the staff of the Manchester Medical Microbiology Partnership; and the research laboratory (in particular, Ali Vaughan) and informatics and project management teams working as part of the Modernising Medical Microbiology consortium (Oxford). We thank Jeff Scott, Ashley Sharp, and Theresa Shryane (Public Health England [PHE] North West) and Suzan Trienekens (Field Epidemiology Service, PHE) for data collection and Karen Mathieson (CMFT), Jane Turton, and Claire Perry (PHE) for outbreak investigation and support. We thank the Health Protection Research Unit Steering Group for review of the draft manuscript. The Transmission of Carbapenemase-producing Enterobacteriaceae (TRACE) study investigators are listed alphabetically, with those also included as named individuals in the author list in parentheses: (Zoie Aiken), (Oluwafemi Akinremi), (Julie Cawthorne), (Paul Cleary), (Derrick W. Crook), (Valerie Decraene), (Andrew Dodgson), Michel Doumith, Matthew Ellington, David W. Eyre, (Ryan George), (Malcolm Guiver), Robert Hill, Katie Hopkins, Rachel Jones, (Cheryl Lenney), (Amy J. Mathers), (Ashley McEwan), Ginny Moore, Sarah Neilson, Tim E. A. Peto, (Hang T. T. Phan), Mark Regan, (Anna C. Seale), (Nicole Stoesser), Jay Turner-Gardner, (Vicky Watts), Jimmy Walker, (A. Sarah Walker), (David H. Wyllie), (William Welfare), and (Neil Woodford). This work was supported by the National Institute for Health Research, Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford University, in partnership with PHE (grant HPRU-2012-10041). The report presents independent research funded by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, or PHE. N.S. is funded by a PHE-University of Oxford Clinical Lectureship. Contemporaneous outbreak investigation by CMFT and PHE was undertaken as part of routine activity. We have no conflicts of interest to declare.

Publisher Copyright:
© 2018 American Society for Microbiology. All Rights Reserved.

Keywords

Antimicrobial resistance
Carbapenemase-producing Enterobacteriaceae
Genome sequencing
Infection control
Molecular epidemiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{3bde301181c4475e937a90b8ff5ecc4e,

title = "A large, refractory nosocomial outbreak of klebsiella pneumoniae carbapenemase-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control",

abstract = "Carbapenem-resistant Enterobacteriaceae (CRE) represent a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly being highlighted as important potential reservoirs. We investigated a large Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli outbreak and wider CRE incidence trends in the Central Manchester University Hospital NHS Foundation Trust (CMFT) (United Kingdom) over 8 years, to determine the impact of infection prevention and control measures. Bacteriology and patient administration data (2009 to 2017) were linked, and a subset of CMFT or regional hospital KPC-producing E. coli isolates (n 268) were sequenced. Control interventions followed international guidelines and included cohorting, rectal screening (n 184,539 screens), environmental sampling, enhanced cleaning, and ward closure and plumbing replacement. Segmented regression of time trends for CRE detections was used to evaluate the impact of interventions on CRE incidence. Genomic analysis (n 268 isolates) identified the spread of a KPC-producing E. coli outbreak clone (strain A, sequence type 216 [ST216]; n 125) among patients and in the environment, particularly on 2 cardiac wards (wards 3 and 4), despite control measures. ST216 strain A had caused an antecedent outbreak and shared its KPC plasmids with other E. coli lineages and Enterobacteriaceae species. CRE acquisition incidence declined after closure of wards 3 and 4 and plumbing replacement, suggesting an environmental contribution. However, ward 3/ward 4 wastewater sites were rapidly recolonized with CRE and patient CRE acquisitions recurred, albeit at lower rates. Patient relocation and plumbing replacement were associated with control of a clonal KPC-producing E. coli outbreak; however, environmental contamination with CRE and patient CRE acquisitions recurred rapidly following this intervention. The large numbers of cases and the persistence of blaKPC in E. coli, including pathogenic lineages, are of concern.",

keywords = "Antimicrobial resistance, Carbapenemase-producing Enterobacteriaceae, Genome sequencing, Infection control, Molecular epidemiology",

author = "{the TRACE Investigators{\textquoteright} Group} and V. Decraene and Phan, {H. T.T.} and R. George and Wyllie, {D. H.} and O. Akinremi and Z. Aiken and Paul Cleary and A. Dodgson and L. Pankhurst and Crook, {D. W.} and C. Lenney and Walker, {A. S.} and Neil Woodford and R. Sebra and F. Fath-Ordoubadi and Mathers, {A. J.} and Seale, {A. C.} and Malcolm Guiver and A. McEwan and V. Watts and William Welfare and N. Stoesser and J. Cawthorne",

note = "Funding Information: We are grateful for and acknowledge the contributions of the clinical and support staff working in the MHC, CMFT; the microbiology laboratory staff and infection control teams at CMFT; the staff of the Manchester Medical Microbiology Partnership; and the research laboratory (in particular, Ali Vaughan) and informatics and project management teams working as part of the Modernising Medical Microbiology consortium (Oxford). We thank Jeff Scott, Ashley Sharp, and Theresa Shryane (Public Health England [PHE] North West) and Suzan Trienekens (Field Epidemiology Service, PHE) for data collection and Karen Mathieson (CMFT), Jane Turton, and Claire Perry (PHE) for outbreak investigation and support. We thank the Health Protection Research Unit Steering Group for review of the draft manuscript. This work was supported by the National Institute for Health Research, Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford University, in partnership with PHE (grant HPRU-2012-10041). The report presents independent research funded by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, or PHE. N.S. is funded by a PHE-University of Oxford Clinical Lectureship. Contemporaneous outbreak investigation by CMFT and PHE was undertaken as part of routine activity. Funding Information: We are grateful for and acknowledge the contributions of the clinical and support staff working in the MHC, CMFT; the microbiology laboratory staff and infection control teams at CMFT; the staff of the Manchester Medical Microbiology Partnership; and the research laboratory (in particular, Ali Vaughan) and informatics and project management teams working as part of the Modernising Medical Microbiology consortium (Oxford). We thank Jeff Scott, Ashley Sharp, and Theresa Shryane (Public Health England [PHE] North West) and Suzan Trienekens (Field Epidemiology Service, PHE) for data collection and Karen Mathieson (CMFT), Jane Turton, and Claire Perry (PHE) for outbreak investigation and support. We thank the Health Protection Research Unit Steering Group for review of the draft manuscript. The Transmission of Carbapenemase-producing Enterobacteriaceae (TRACE) study investigators are listed alphabetically, with those also included as named individuals in the author list in parentheses: (Zoie Aiken), (Oluwafemi Akinremi), (Julie Cawthorne), (Paul Cleary), (Derrick W. Crook), (Valerie Decraene), (Andrew Dodgson), Michel Doumith, Matthew Ellington, David W. Eyre, (Ryan George), (Malcolm Guiver), Robert Hill, Katie Hopkins, Rachel Jones, (Cheryl Lenney), (Amy J. Mathers), (Ashley McEwan), Ginny Moore, Sarah Neilson, Tim E. A. Peto, (Hang T. T. Phan), Mark Regan, (Anna C. Seale), (Nicole Stoesser), Jay Turner-Gardner, (Vicky Watts), Jimmy Walker, (A. Sarah Walker), (David H. Wyllie), (William Welfare), and (Neil Woodford). This work was supported by the National Institute for Health Research, Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford University, in partnership with PHE (grant HPRU-2012-10041). The report presents independent research funded by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, or PHE. N.S. is funded by a PHE-University of Oxford Clinical Lectureship. Contemporaneous outbreak investigation by CMFT and PHE was undertaken as part of routine activity. We have no conflicts of interest to declare. Publisher Copyright: {\textcopyright} 2018 American Society for Microbiology. All Rights Reserved.",

year = "2018",

month = dec,

doi = "10.1128/AAC.01689-18",

language = "English",

volume = "62",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "12",

}

A large, refractory nosocomial outbreak of klebsiella pneumoniae carbapenemase-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control. / the TRACE Investigators’ Group.
In: Antimicrobial Agents and Chemotherapy, Vol. 62, No. 12, e01689-18, 12.2018.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A large, refractory nosocomial outbreak of klebsiella pneumoniae carbapenemase-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control

AU - the TRACE Investigators’ Group

AU - Decraene, V.

AU - Phan, H. T.T.

AU - George, R.

AU - Wyllie, D. H.

AU - Akinremi, O.

AU - Aiken, Z.

AU - Cleary, Paul

AU - Dodgson, A.

AU - Pankhurst, L.

AU - Crook, D. W.

AU - Lenney, C.

AU - Walker, A. S.

AU - Woodford, Neil

AU - Sebra, R.

AU - Fath-Ordoubadi, F.

AU - Mathers, A. J.

AU - Seale, A. C.

AU - Guiver, Malcolm

AU - McEwan, A.

AU - Watts, V.

AU - Welfare, William

AU - Stoesser, N.

AU - Cawthorne, J.

N1 - Funding Information: We are grateful for and acknowledge the contributions of the clinical and support staff working in the MHC, CMFT; the microbiology laboratory staff and infection control teams at CMFT; the staff of the Manchester Medical Microbiology Partnership; and the research laboratory (in particular, Ali Vaughan) and informatics and project management teams working as part of the Modernising Medical Microbiology consortium (Oxford). We thank Jeff Scott, Ashley Sharp, and Theresa Shryane (Public Health England [PHE] North West) and Suzan Trienekens (Field Epidemiology Service, PHE) for data collection and Karen Mathieson (CMFT), Jane Turton, and Claire Perry (PHE) for outbreak investigation and support. We thank the Health Protection Research Unit Steering Group for review of the draft manuscript. This work was supported by the National Institute for Health Research, Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford University, in partnership with PHE (grant HPRU-2012-10041). The report presents independent research funded by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, or PHE. N.S. is funded by a PHE-University of Oxford Clinical Lectureship. Contemporaneous outbreak investigation by CMFT and PHE was undertaken as part of routine activity. Funding Information: We are grateful for and acknowledge the contributions of the clinical and support staff working in the MHC, CMFT; the microbiology laboratory staff and infection control teams at CMFT; the staff of the Manchester Medical Microbiology Partnership; and the research laboratory (in particular, Ali Vaughan) and informatics and project management teams working as part of the Modernising Medical Microbiology consortium (Oxford). We thank Jeff Scott, Ashley Sharp, and Theresa Shryane (Public Health England [PHE] North West) and Suzan Trienekens (Field Epidemiology Service, PHE) for data collection and Karen Mathieson (CMFT), Jane Turton, and Claire Perry (PHE) for outbreak investigation and support. We thank the Health Protection Research Unit Steering Group for review of the draft manuscript. The Transmission of Carbapenemase-producing Enterobacteriaceae (TRACE) study investigators are listed alphabetically, with those also included as named individuals in the author list in parentheses: (Zoie Aiken), (Oluwafemi Akinremi), (Julie Cawthorne), (Paul Cleary), (Derrick W. Crook), (Valerie Decraene), (Andrew Dodgson), Michel Doumith, Matthew Ellington, David W. Eyre, (Ryan George), (Malcolm Guiver), Robert Hill, Katie Hopkins, Rachel Jones, (Cheryl Lenney), (Amy J. Mathers), (Ashley McEwan), Ginny Moore, Sarah Neilson, Tim E. A. Peto, (Hang T. T. Phan), Mark Regan, (Anna C. Seale), (Nicole Stoesser), Jay Turner-Gardner, (Vicky Watts), Jimmy Walker, (A. Sarah Walker), (David H. Wyllie), (William Welfare), and (Neil Woodford). This work was supported by the National Institute for Health Research, Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford University, in partnership with PHE (grant HPRU-2012-10041). The report presents independent research funded by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, or PHE. N.S. is funded by a PHE-University of Oxford Clinical Lectureship. Contemporaneous outbreak investigation by CMFT and PHE was undertaken as part of routine activity. We have no conflicts of interest to declare. Publisher Copyright: © 2018 American Society for Microbiology. All Rights Reserved.

PY - 2018/12

Y1 - 2018/12

N2 - Carbapenem-resistant Enterobacteriaceae (CRE) represent a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly being highlighted as important potential reservoirs. We investigated a large Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli outbreak and wider CRE incidence trends in the Central Manchester University Hospital NHS Foundation Trust (CMFT) (United Kingdom) over 8 years, to determine the impact of infection prevention and control measures. Bacteriology and patient administration data (2009 to 2017) were linked, and a subset of CMFT or regional hospital KPC-producing E. coli isolates (n 268) were sequenced. Control interventions followed international guidelines and included cohorting, rectal screening (n 184,539 screens), environmental sampling, enhanced cleaning, and ward closure and plumbing replacement. Segmented regression of time trends for CRE detections was used to evaluate the impact of interventions on CRE incidence. Genomic analysis (n 268 isolates) identified the spread of a KPC-producing E. coli outbreak clone (strain A, sequence type 216 [ST216]; n 125) among patients and in the environment, particularly on 2 cardiac wards (wards 3 and 4), despite control measures. ST216 strain A had caused an antecedent outbreak and shared its KPC plasmids with other E. coli lineages and Enterobacteriaceae species. CRE acquisition incidence declined after closure of wards 3 and 4 and plumbing replacement, suggesting an environmental contribution. However, ward 3/ward 4 wastewater sites were rapidly recolonized with CRE and patient CRE acquisitions recurred, albeit at lower rates. Patient relocation and plumbing replacement were associated with control of a clonal KPC-producing E. coli outbreak; however, environmental contamination with CRE and patient CRE acquisitions recurred rapidly following this intervention. The large numbers of cases and the persistence of blaKPC in E. coli, including pathogenic lineages, are of concern.

AB - Carbapenem-resistant Enterobacteriaceae (CRE) represent a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly being highlighted as important potential reservoirs. We investigated a large Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli outbreak and wider CRE incidence trends in the Central Manchester University Hospital NHS Foundation Trust (CMFT) (United Kingdom) over 8 years, to determine the impact of infection prevention and control measures. Bacteriology and patient administration data (2009 to 2017) were linked, and a subset of CMFT or regional hospital KPC-producing E. coli isolates (n 268) were sequenced. Control interventions followed international guidelines and included cohorting, rectal screening (n 184,539 screens), environmental sampling, enhanced cleaning, and ward closure and plumbing replacement. Segmented regression of time trends for CRE detections was used to evaluate the impact of interventions on CRE incidence. Genomic analysis (n 268 isolates) identified the spread of a KPC-producing E. coli outbreak clone (strain A, sequence type 216 [ST216]; n 125) among patients and in the environment, particularly on 2 cardiac wards (wards 3 and 4), despite control measures. ST216 strain A had caused an antecedent outbreak and shared its KPC plasmids with other E. coli lineages and Enterobacteriaceae species. CRE acquisition incidence declined after closure of wards 3 and 4 and plumbing replacement, suggesting an environmental contribution. However, ward 3/ward 4 wastewater sites were rapidly recolonized with CRE and patient CRE acquisitions recurred, albeit at lower rates. Patient relocation and plumbing replacement were associated with control of a clonal KPC-producing E. coli outbreak; however, environmental contamination with CRE and patient CRE acquisitions recurred rapidly following this intervention. The large numbers of cases and the persistence of blaKPC in E. coli, including pathogenic lineages, are of concern.

KW - Antimicrobial resistance

KW - Carbapenemase-producing Enterobacteriaceae

KW - Genome sequencing

KW - Infection control

KW - Molecular epidemiology

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U2 - 10.1128/AAC.01689-18

DO - 10.1128/AAC.01689-18

M3 - Article

C2 - 30249685

AN - SCOPUS:85057146436

SN - 0066-4804

VL - 62

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 12

M1 - e01689-18

ER -

A large, refractory nosocomial outbreak of klebsiella pneumoniae carbapenemase-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control

Abstract

Bibliographical note

Keywords

UN SDGs

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