Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region

Brian D Johnston; Paul Thuras; Stephen B. Porter; Mariana Castanheira; James R Johnson

doi:10.1016/j.jgar.2020.12.017

Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region

Brian D Johnston, Paul Thuras, Stephen B. Porter, Mariana Castanheira, James R Johnson

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

9 Scopus citations

Abstract

Objectives: Carbapenem resistance has emerged inEscherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. Meropenem/vaborbactam (MVB) is a recently approved carbapenem/β-lactamase inhibitor combination with broad-spectrum inhibition of β-lactamases, including serine carbapenemases. The activity of MVB against carbapenem-resistant (CR) E. coli infections in relation to phylogenetic background, resistance genotype and geographical region is unknown. Methods: We characterised 140 contemporary CR clinicalE. coli isolates from 17 non-US countries (2003–2017) for phylogroup, clonal group (including ST131, H30R and the CTX-M-15-associated H30Rx subset), relevant β-lactamase genes, and broth microdilution MICs for MVB and 11 comparators. Results: Overall, MVB was moderately active (66% susceptible), more so than all comparators except tigecycline and amikacin (100% and 74% susceptible, respectively). Most MVB-non-susceptible isolates carried metallo-β-lactamase or OXA-48 resistance genes. MVB's activity varied significantly in relation to phylogroup, clonal background, resistance genotype and global region: it was greatest among phylogroup F, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive and Latin American isolates, and lowest among phylogroup B1, metallo-β-lactamase gene-containing and Asia-West Pacific region isolates. Enhancement of meropenem's activity by vaborbactam was most evident for isolates from phylogroups B2, C and D, and those containing KPC. MVB retained appreciable (albeit somewhat reduced) activity against isolates resistant to comparator agents. Conclusion: MVB should be useful for treating international CRE. coli infections, largely independent of other resistance phenotypes, although this likely will vary with the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.

Original language	English (US)
Pages (from-to)	190-197
Number of pages	8
Journal	Journal of Global Antimicrobial Resistance
Volume	24
DOIs	https://doi.org/10.1016/j.jgar.2020.12.017
State	Published - Mar 2021

Bibliographical note

Funding Information:
This work was supported in part by an investigator-initiated research grant from Melinta and by the Department of Veterans Affairs, Office of Research and Development [grant # 2I01CX000920-04 to JRJ]. The funders had no control over the content of the report or the decision to publish. The opinions expressed are those of the authors and not necessarily those of the authors’ institutions or the Department of Veterans Affairs.

Publisher Copyright:
© 2021 The Author(s)

Keywords

Carbapenem resistance
Escherichia coli
Klebsiella pneumoniae carbapenemase
Meropenem/vaborbactam
New Delhi metallo-β-lactamase
ST131

UN SDGs

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

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Johnston, B. D., Thuras, P., Porter, S. B., Castanheira, M., & Johnson, J. R. (2021). Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region. Journal of Global Antimicrobial Resistance, 24, 190-197. https://doi.org/10.1016/j.jgar.2020.12.017

Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region. / Johnston, Brian D; Thuras, Paul; Porter, Stephen B. et al.
In: Journal of Global Antimicrobial Resistance, Vol. 24, 03.2021, p. 190-197.

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

Johnston, BD, Thuras, P, Porter, SB, Castanheira, M & Johnson, JR 2021, 'Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region', Journal of Global Antimicrobial Resistance, vol. 24, pp. 190-197. https://doi.org/10.1016/j.jgar.2020.12.017

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abstract = "Objectives: Carbapenem resistance has emerged inEscherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. Meropenem/vaborbactam (MVB) is a recently approved carbapenem/β-lactamase inhibitor combination with broad-spectrum inhibition of β-lactamases, including serine carbapenemases. The activity of MVB against carbapenem-resistant (CR) E. coli infections in relation to phylogenetic background, resistance genotype and geographical region is unknown. Methods: We characterised 140 contemporary CR clinicalE. coli isolates from 17 non-US countries (2003–2017) for phylogroup, clonal group (including ST131, H30R and the CTX-M-15-associated H30Rx subset), relevant β-lactamase genes, and broth microdilution MICs for MVB and 11 comparators. Results: Overall, MVB was moderately active (66% susceptible), more so than all comparators except tigecycline and amikacin (100% and 74% susceptible, respectively). Most MVB-non-susceptible isolates carried metallo-β-lactamase or OXA-48 resistance genes. MVB's activity varied significantly in relation to phylogroup, clonal background, resistance genotype and global region: it was greatest among phylogroup F, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive and Latin American isolates, and lowest among phylogroup B1, metallo-β-lactamase gene-containing and Asia-West Pacific region isolates. Enhancement of meropenem's activity by vaborbactam was most evident for isolates from phylogroups B2, C and D, and those containing KPC. MVB retained appreciable (albeit somewhat reduced) activity against isolates resistant to comparator agents. Conclusion: MVB should be useful for treating international CRE. coli infections, largely independent of other resistance phenotypes, although this likely will vary with the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.",

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doi = "10.1016/j.jgar.2020.12.017",

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AU - Thuras, Paul

AU - Porter, Stephen B.

AU - Castanheira, Mariana

AU - Johnson, James R

N1 - Funding Information: This work was supported in part by an investigator-initiated research grant from Melinta and by the Department of Veterans Affairs, Office of Research and Development [grant # 2I01CX000920-04 to JRJ]. The funders had no control over the content of the report or the decision to publish. The opinions expressed are those of the authors and not necessarily those of the authors’ institutions or the Department of Veterans Affairs. Publisher Copyright: © 2021 The Author(s)

PY - 2021/3

Y1 - 2021/3

N2 - Objectives: Carbapenem resistance has emerged inEscherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. Meropenem/vaborbactam (MVB) is a recently approved carbapenem/β-lactamase inhibitor combination with broad-spectrum inhibition of β-lactamases, including serine carbapenemases. The activity of MVB against carbapenem-resistant (CR) E. coli infections in relation to phylogenetic background, resistance genotype and geographical region is unknown. Methods: We characterised 140 contemporary CR clinicalE. coli isolates from 17 non-US countries (2003–2017) for phylogroup, clonal group (including ST131, H30R and the CTX-M-15-associated H30Rx subset), relevant β-lactamase genes, and broth microdilution MICs for MVB and 11 comparators. Results: Overall, MVB was moderately active (66% susceptible), more so than all comparators except tigecycline and amikacin (100% and 74% susceptible, respectively). Most MVB-non-susceptible isolates carried metallo-β-lactamase or OXA-48 resistance genes. MVB's activity varied significantly in relation to phylogroup, clonal background, resistance genotype and global region: it was greatest among phylogroup F, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive and Latin American isolates, and lowest among phylogroup B1, metallo-β-lactamase gene-containing and Asia-West Pacific region isolates. Enhancement of meropenem's activity by vaborbactam was most evident for isolates from phylogroups B2, C and D, and those containing KPC. MVB retained appreciable (albeit somewhat reduced) activity against isolates resistant to comparator agents. Conclusion: MVB should be useful for treating international CRE. coli infections, largely independent of other resistance phenotypes, although this likely will vary with the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.

AB - Objectives: Carbapenem resistance has emerged inEscherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. Meropenem/vaborbactam (MVB) is a recently approved carbapenem/β-lactamase inhibitor combination with broad-spectrum inhibition of β-lactamases, including serine carbapenemases. The activity of MVB against carbapenem-resistant (CR) E. coli infections in relation to phylogenetic background, resistance genotype and geographical region is unknown. Methods: We characterised 140 contemporary CR clinicalE. coli isolates from 17 non-US countries (2003–2017) for phylogroup, clonal group (including ST131, H30R and the CTX-M-15-associated H30Rx subset), relevant β-lactamase genes, and broth microdilution MICs for MVB and 11 comparators. Results: Overall, MVB was moderately active (66% susceptible), more so than all comparators except tigecycline and amikacin (100% and 74% susceptible, respectively). Most MVB-non-susceptible isolates carried metallo-β-lactamase or OXA-48 resistance genes. MVB's activity varied significantly in relation to phylogroup, clonal background, resistance genotype and global region: it was greatest among phylogroup F, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive and Latin American isolates, and lowest among phylogroup B1, metallo-β-lactamase gene-containing and Asia-West Pacific region isolates. Enhancement of meropenem's activity by vaborbactam was most evident for isolates from phylogroups B2, C and D, and those containing KPC. MVB retained appreciable (albeit somewhat reduced) activity against isolates resistant to comparator agents. Conclusion: MVB should be useful for treating international CRE. coli infections, largely independent of other resistance phenotypes, although this likely will vary with the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.

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KW - Escherichia coli

KW - Klebsiella pneumoniae carbapenemase

KW - Meropenem/vaborbactam

KW - New Delhi metallo-β-lactamase

KW - ST131

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Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region

Abstract

Bibliographical note

Keywords

UN SDGs

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