Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK: Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK)

Neil Woodford; Li Xu-McCrae; Shazad Mushtaq; Houdini Ho Tin Wu; Matthew Ellington; Owen Lancaster; Frances Davies; Hugo Donaldson; G. Gopal Rao; Anita Verma; David W. Wareham; Holly Ciesielczuk; Gregory G. Stone; Paurus M. Irani; Simon Bracher; Peter Hawkey

doi:10.1093/jac/dkx471

Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK: Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK)

Neil Woodford^*, Li Xu-McCrae, Shazad Mushtaq, Houdini Ho Tin Wu, Matthew Ellington, Owen Lancaster, Frances Davies, Hugo Donaldson, G. Gopal Rao, Anita Verma, David W. Wareham, Holly Ciesielczuk, Gregory G. Stone, Paurus M. Irani, Simon Bracher, Peter Hawkey

^*Corresponding author for this work

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

18 Citations (Scopus)

Abstract

Objectives: Although carbapenem susceptibility testing has been recommended for all Enterobacteriaceae from clinical specimens, for practical reasons a carbapenem is not included in many primary antibiotic panels for urine specimens. The 'iCREST' study sought carbapenemase-producing Enterobacteriaceae (CPE) in routine urine specimens yielding Gram-negative growth in five diagnostic laboratories in the UK. We sought also to compare locally and centrally determined MICs of meropenemand ceftazidime/avibactam. Methods: Positive growth from up to 2000 urine specimens per laboratory was plated onto chromID® CARBA SMART agar. Suspected CPE colonies were tested locally by Etest for susceptibility to meropenem and ceftazidime/ avibactam, and referred to central laboratories for PCR confirmation of CPE status and microbroth MIC determination. Results: Twenty-two suspected CPE were identified from 7504 urine specimens. Ten were confirmed by PCR to have NDM (5), IMP (2), KPC (2) or OXA-48-like (1) carbapenemases. Locally determined ceftazidime/avibactam MICs showed complete categorical agreement with those determined centrally by microbroth methodology. The seven ceftazidime/avibactam-resistant isolates (MICs≥256mg/L) had NDMor IMPmetallo-carbapenemases. Conclusions: The frequency of confirmed CPE among Gram-negative urinary isolates was low, at 0.13% (10/7504), but CPE were found in urines at all five participating sites and the diversity of carbapenemase genes detected reflected the complex epidemiology of CPE in the UK. These data can inform local policies about the cost-effectiveness and clinical value of testing Gram-negative bacteria from urine specimens routinely against a carbapenem as part of patient management and/or infection prevention and control strategies.

Original language	English
Pages (from-to)	698-702
Number of pages	5
Journal	Journal of Antimicrobial Chemotherapy
Volume	73
Issue number	3
DOIs	https://doi.org/10.1093/jac/dkx471
Publication status	Published - 1 Mar 2018

Bibliographical note

Funding Information:
G. G. S. and P. M. I. were employees of AstraZeneca, now Pfizer. S. B. received consultation fees from AstraZeneca in relation to this study. All other authors have no personal transparency declarations to make. PHE’s AMRHAI Reference Unit has received financial support for conference attendance, lectures, research projects or contracted evaluations from numerous sources, including: Accelerate, Achaogen, Allecra, Amplex, AstraZeneca, Basilea, Becton Dickinson Diagnostics, bioMérieux, Bio-Rad Laboratories, BSAC, Cepheid, Check-Points, Cubist Pharmaceuticals, Department of Health, Enigma Diagnostics, Food Standards Agency, GlaxoSmithKline, Henry Stewart Talks, IHMA, Kalidex, Melinta, Merck Sharpe & Dohme, Meiji, Mobidiag, Momentum Biosciences, Nordic, Norgine, Rempex, Roche, Rokitan, Smith & Nephew, Trius, VenatoRx and Wockhardt.

Funding Information:
This study and the associated database and medical writing costs were sponsored by AstraZeneca.

Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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Woodford, N., Xu-McCrae, L., Mushtaq, S., Wu, H. H. T., Ellington, M., Lancaster, O., Davies, F., Donaldson, H., Gopal Rao, G., Verma, A., Wareham, D. W., Ciesielczuk, H., Stone, G. G., Irani, P. M., Bracher, S., & Hawkey, P. (2018). Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK: Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK). Journal of Antimicrobial Chemotherapy, 73(3), 698-702. https://doi.org/10.1093/jac/dkx471

@article{704555e024894ed9a8fa6bf80e20d1a6,

title = "Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK: Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK)",

abstract = "Objectives: Although carbapenem susceptibility testing has been recommended for all Enterobacteriaceae from clinical specimens, for practical reasons a carbapenem is not included in many primary antibiotic panels for urine specimens. The 'iCREST' study sought carbapenemase-producing Enterobacteriaceae (CPE) in routine urine specimens yielding Gram-negative growth in five diagnostic laboratories in the UK. We sought also to compare locally and centrally determined MICs of meropenemand ceftazidime/avibactam. Methods: Positive growth from up to 2000 urine specimens per laboratory was plated onto chromID{\textregistered} CARBA SMART agar. Suspected CPE colonies were tested locally by Etest for susceptibility to meropenem and ceftazidime/ avibactam, and referred to central laboratories for PCR confirmation of CPE status and microbroth MIC determination. Results: Twenty-two suspected CPE were identified from 7504 urine specimens. Ten were confirmed by PCR to have NDM (5), IMP (2), KPC (2) or OXA-48-like (1) carbapenemases. Locally determined ceftazidime/avibactam MICs showed complete categorical agreement with those determined centrally by microbroth methodology. The seven ceftazidime/avibactam-resistant isolates (MICs≥256mg/L) had NDMor IMPmetallo-carbapenemases. Conclusions: The frequency of confirmed CPE among Gram-negative urinary isolates was low, at 0.13% (10/7504), but CPE were found in urines at all five participating sites and the diversity of carbapenemase genes detected reflected the complex epidemiology of CPE in the UK. These data can inform local policies about the cost-effectiveness and clinical value of testing Gram-negative bacteria from urine specimens routinely against a carbapenem as part of patient management and/or infection prevention and control strategies.",

author = "Neil Woodford and Li Xu-McCrae and Shazad Mushtaq and Wu, {Houdini Ho Tin} and Matthew Ellington and Owen Lancaster and Frances Davies and Hugo Donaldson and {Gopal Rao}, G. and Anita Verma and Wareham, {David W.} and Holly Ciesielczuk and Stone, {Gregory G.} and Irani, {Paurus M.} and Simon Bracher and Peter Hawkey",

note = "Funding Information: G. G. S. and P. M. I. were employees of AstraZeneca, now Pfizer. S. B. received consultation fees from AstraZeneca in relation to this study. All other authors have no personal transparency declarations to make. PHE{\textquoteright}s AMRHAI Reference Unit has received financial support for conference attendance, lectures, research projects or contracted evaluations from numerous sources, including: Accelerate, Achaogen, Allecra, Amplex, AstraZeneca, Basilea, Becton Dickinson Diagnostics, bioM{\'e}rieux, Bio-Rad Laboratories, BSAC, Cepheid, Check-Points, Cubist Pharmaceuticals, Department of Health, Enigma Diagnostics, Food Standards Agency, GlaxoSmithKline, Henry Stewart Talks, IHMA, Kalidex, Melinta, Merck Sharpe & Dohme, Meiji, Mobidiag, Momentum Biosciences, Nordic, Norgine, Rempex, Roche, Rokitan, Smith & Nephew, Trius, VenatoRx and Wockhardt. Funding Information: This study and the associated database and medical writing costs were sponsored by AstraZeneca. Publisher Copyright: {\textcopyright} The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.",

year = "2018",

month = mar,

day = "1",

doi = "10.1093/jac/dkx471",

language = "English",

volume = "73",

pages = "698--702",

journal = "Journal of Antimicrobial Chemotherapy",

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Woodford, N, Xu-McCrae, L, Mushtaq, S, Wu, HHT, Ellington, M, Lancaster, O, Davies, F, Donaldson, H, Gopal Rao, G, Verma, A, Wareham, DW, Ciesielczuk, H, Stone, GG, Irani, PM, Bracher, S & Hawkey, P 2018, 'Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK: Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK)', Journal of Antimicrobial Chemotherapy, vol. 73, no. 3, pp. 698-702. https://doi.org/10.1093/jac/dkx471

Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK: Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK). / Woodford, Neil; Xu-McCrae, Li; Mushtaq, Shazad et al.
In: Journal of Antimicrobial Chemotherapy, Vol. 73, No. 3, 01.03.2018, p. 698-702.

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

TY - JOUR

T1 - Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK

T2 - Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK)

AU - Woodford, Neil

AU - Xu-McCrae, Li

AU - Mushtaq, Shazad

AU - Wu, Houdini Ho Tin

AU - Ellington, Matthew

AU - Lancaster, Owen

AU - Davies, Frances

AU - Donaldson, Hugo

AU - Gopal Rao, G.

AU - Verma, Anita

AU - Wareham, David W.

AU - Ciesielczuk, Holly

AU - Stone, Gregory G.

AU - Irani, Paurus M.

AU - Bracher, Simon

AU - Hawkey, Peter

N1 - Funding Information: G. G. S. and P. M. I. were employees of AstraZeneca, now Pfizer. S. B. received consultation fees from AstraZeneca in relation to this study. All other authors have no personal transparency declarations to make. PHE’s AMRHAI Reference Unit has received financial support for conference attendance, lectures, research projects or contracted evaluations from numerous sources, including: Accelerate, Achaogen, Allecra, Amplex, AstraZeneca, Basilea, Becton Dickinson Diagnostics, bioMérieux, Bio-Rad Laboratories, BSAC, Cepheid, Check-Points, Cubist Pharmaceuticals, Department of Health, Enigma Diagnostics, Food Standards Agency, GlaxoSmithKline, Henry Stewart Talks, IHMA, Kalidex, Melinta, Merck Sharpe & Dohme, Meiji, Mobidiag, Momentum Biosciences, Nordic, Norgine, Rempex, Roche, Rokitan, Smith & Nephew, Trius, VenatoRx and Wockhardt. Funding Information: This study and the associated database and medical writing costs were sponsored by AstraZeneca. Publisher Copyright: © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Objectives: Although carbapenem susceptibility testing has been recommended for all Enterobacteriaceae from clinical specimens, for practical reasons a carbapenem is not included in many primary antibiotic panels for urine specimens. The 'iCREST' study sought carbapenemase-producing Enterobacteriaceae (CPE) in routine urine specimens yielding Gram-negative growth in five diagnostic laboratories in the UK. We sought also to compare locally and centrally determined MICs of meropenemand ceftazidime/avibactam. Methods: Positive growth from up to 2000 urine specimens per laboratory was plated onto chromID® CARBA SMART agar. Suspected CPE colonies were tested locally by Etest for susceptibility to meropenem and ceftazidime/ avibactam, and referred to central laboratories for PCR confirmation of CPE status and microbroth MIC determination. Results: Twenty-two suspected CPE were identified from 7504 urine specimens. Ten were confirmed by PCR to have NDM (5), IMP (2), KPC (2) or OXA-48-like (1) carbapenemases. Locally determined ceftazidime/avibactam MICs showed complete categorical agreement with those determined centrally by microbroth methodology. The seven ceftazidime/avibactam-resistant isolates (MICs≥256mg/L) had NDMor IMPmetallo-carbapenemases. Conclusions: The frequency of confirmed CPE among Gram-negative urinary isolates was low, at 0.13% (10/7504), but CPE were found in urines at all five participating sites and the diversity of carbapenemase genes detected reflected the complex epidemiology of CPE in the UK. These data can inform local policies about the cost-effectiveness and clinical value of testing Gram-negative bacteria from urine specimens routinely against a carbapenem as part of patient management and/or infection prevention and control strategies.

AB - Objectives: Although carbapenem susceptibility testing has been recommended for all Enterobacteriaceae from clinical specimens, for practical reasons a carbapenem is not included in many primary antibiotic panels for urine specimens. The 'iCREST' study sought carbapenemase-producing Enterobacteriaceae (CPE) in routine urine specimens yielding Gram-negative growth in five diagnostic laboratories in the UK. We sought also to compare locally and centrally determined MICs of meropenemand ceftazidime/avibactam. Methods: Positive growth from up to 2000 urine specimens per laboratory was plated onto chromID® CARBA SMART agar. Suspected CPE colonies were tested locally by Etest for susceptibility to meropenem and ceftazidime/ avibactam, and referred to central laboratories for PCR confirmation of CPE status and microbroth MIC determination. Results: Twenty-two suspected CPE were identified from 7504 urine specimens. Ten were confirmed by PCR to have NDM (5), IMP (2), KPC (2) or OXA-48-like (1) carbapenemases. Locally determined ceftazidime/avibactam MICs showed complete categorical agreement with those determined centrally by microbroth methodology. The seven ceftazidime/avibactam-resistant isolates (MICs≥256mg/L) had NDMor IMPmetallo-carbapenemases. Conclusions: The frequency of confirmed CPE among Gram-negative urinary isolates was low, at 0.13% (10/7504), but CPE were found in urines at all five participating sites and the diversity of carbapenemase genes detected reflected the complex epidemiology of CPE in the UK. These data can inform local policies about the cost-effectiveness and clinical value of testing Gram-negative bacteria from urine specimens routinely against a carbapenem as part of patient management and/or infection prevention and control strategies.

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Woodford N, Xu-McCrae L, Mushtaq S, Wu HHT, Ellington M, Lancaster O et al. Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK: Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK). Journal of Antimicrobial Chemotherapy. 2018 Mar 1;73(3):698-702. doi: 10.1093/jac/dkx471

Prevalence of carbapenem resistance and carbapenemase production among Enterobacteriaceae isolated from urine in the UK: Results of the UK infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-UK)

Abstract

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