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Global molecular epidemiology of carbapenem-resistant Escherichia coli (2002–2017)

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Abstract

The emergence of carbapenem-resistant (CR) Escherichia coli obliges an assessment of such strains’ molecular epidemiology. Accordingly, we characterized in detail a globally distributed collection of CR E. coli isolates, then explored for associations between geographical origin and bacterial traits, and between different bacterial traits. We used established PCR-based assays and broth microdilution MIC determinations to characterize 343 global CR (i.e., non-susceptible to ≥ 1 carbapenem) extraintestinal E. coli isolates (2002–2017) for diverse molecular traits—including phylogroups, sequence types (STs), beta-lactamase genes, and 51 virulence genes—and susceptibility to 12 relevant antimicrobial agents. The study population was tremendously diverse according to all assessed variables. Nonetheless, certain geographically aligned, unifying themes emerged. These included an association of an Asia/West Pacific origin with non-B2/D/F phylogroups and STs, lower molecularly inferred virulence, more extensive resistance, and specific resistance genes (notably, metallo-beta-lactamases). Likewise, U.S. isolates from the central region, vs. other regions, were more virulent-appearing and more often from phylogroup B2 and ST131, but less extensively resistant and more often carbapenemase-gene negative. The global CR E. coli population is highly diverse according to multiple characteristics and varies significantly by geographical region. This predictably will pose challenges for prevention and management, and obliges ongoing surveillance.

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The Minnesota Department of Health and JMI Laboratories provided the study isolates.

Funding

This work was supported in part by investigator-initiated grants from Allergan, Cipla/Achaogen, Melinta, Merck, Shionogi, and Tetraphase. It was also supported by Office of Research and Development, Department of Veterans Affairs. The sponsors had no role in study design, data collection, data analysis, writing the manuscript, or the decision to publish.

Author information

Authors and Affiliations

  1. Infectious Diseases (111F), VA Medical Center, Minneapolis VA Health Care System, 1 Veterans Drive, Minneapolis, MN, 55417, USA

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

  2. University of Minnesota, Minneapolis, MN, USA

    Brian D. Johnston, Paul Thuras & James R. Johnson

  3. Minnesota Department of Health, St. Paul, MN, USA

    Melissa Anacker, Brittany VonBank, Paula Snippes Vagnone & Medora Witwer

  4. JMI Laboratories, North Liberty, IA, USA

    Mariana Castanheira

Authors
  1. Brian D. Johnston
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  2. Paul Thuras
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  4. Melissa Anacker
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  6. Paula Snippes Vagnone
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  8. Mariana Castanheira
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  9. James R. Johnson
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Contributions

Brian Johnston: data collection and validation, laboratory procedures, data analysis, construction of tables, manuscript writing and editing.

Paul Thuras: statistical analysis.

Stephen B. Porter: isolate collection, data collection, manuscript editing.

Melissa Anacker: provision of isolates, data collection, manuscript editing.

Brittany VonBank: provision of isolates, data collection, manuscript editing.

Paula Snippes Vagnone: provision of isolates, data collection, manuscript editing.

Medora Witwer: provision of isolates, data collection, manuscript editing.

Mariana Castanheira: provision of isolates, data collection, manuscript editing.

James R. Johnson: concept, funding, project oversight, manuscript writing and editing.

Corresponding author

Correspondence to James R. Johnson.

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Ethics approval

The study was approved by the MVAMC Institutional Review Board.

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Conflict of interest

James R. Johnson has had grants and/or consultancies with Allergan/Actavis, Cipla/Achaogen, Janssen/Crucell, Melinta/The Medicines Company, Merck, Shionogi, Syntiron, and Tetraphase.

Mariana Castanheira is an employee of JMI Laboratories. JMI Laboratories contracted to perform services in 2019 for Achaogen, Inc., Albany College of Pharmacy and Health Sciences, Allecra Therapeutics, Allergan, AmpliPhi Biosciences Corp., Amicrobe Advanced Biomaterials, Amplyx, Antabio, American Proficiency Institute, Arietis Corp., Arixa Pharmaceuticals, Inc., Astellas Pharma Inc., Athelas, Basilea Pharmaceutica Ltd., Bayer AG, Becton, Dickinson and Company, bioMerieux SA, Boston Pharmaceuticals, Bugworks Research Inc., CEM-102 Pharmaceuticals, Cepheid, Cidara Therapeutics, Inc., CorMedix Inc., DePuy Synthes, Destiny Pharma, Discuva Ltd., Dr. Falk Pharma GmbH, Emery Pharma, Entasis Therapeutics, Eurofarma Laboratorios SA, U.S. Food and Drug Administration, Fox Chase Chemical Diversity Center, Inc., Gateway Pharmaceutical LLC, GenePOC Inc., Geom Therapeutics, Inc., GlaxoSmithKline plc, Harvard University, Helperby, HiMedia Laboratories, F. Hoffmann-La Roche Ltd., ICON plc, Idorsia Pharmaceuticals Ltd., Iterum Therapeutics plc, Laboratory Specialists, Inc., Melinta Therapeutics, Inc., Merck & Co., Inc., Microchem Laboratory, Micromyx, MicuRx Pharmaceuticals, Inc., Mutabilis Co., Nabriva Therapeutics plc, NAEJA-RGM, Novartis AG, Oxoid Ltd., Paratek Pharmaceuticals, Inc., Pfizer, Inc., Polyphor Ltd., Pharmaceutical Product Development, LLC, Prokaryotics Inc., Qpex Biopharma, Inc., Roivant Sciences, Ltd., Safeguard Biosystems, Scynexis, Inc., SeLux Diagnostics, Inc., Shionogi and Co., Ltd., SinSa Labs, Spero Therapeutics, Summit Pharmaceuticals International Corp., Synlogic, T2 Biosystems, Inc., Taisho Pharmaceutical Co., Ltd., TenNor Therapeutics Ltd., Tetraphase Pharmaceuticals, Theravance Biopharma, University of Colorado, University of Southern California-San Diego, University of North Texas Health Science Center, VenatoRx Pharmaceuticals, Inc., Viosera Therapeutics, Vyome Therapeutics Inc., Wockhardt, Yukon Pharmaceuticals, Inc., Zai Lab, and Zavante Therapeutics, Inc. She has no speakers’ bureaus or stock options to declare.

The other authors report no financial conflicts of interest.

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Johnston, B.D., Thuras, P., Porter, S.B. et al. Global molecular epidemiology of carbapenem-resistant Escherichia coli (2002–2017). Eur J Clin Microbiol Infect Dis (2021). https://doi.org/10.1007/s10096-021-04310-6

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