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Comparative activity of plazomicin against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012–2017) in relation to phylogenetic background, sequence type 131 subclones, blaCTX-M genotype, and resistance to comparator agents

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Abstract

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (blaCTX-M-15-associated) H30Rx subclone and (blaCTX-M-27-associated) C1-M27 subset within the H30R1 subclone. The comparative activity against such strains of alternative antimicrobial agents, including the recently developed aminoglycoside plazomicin, is undefined, so was investigated here. We assessed plazomicin and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012–2017) and then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (blaCTX-M; group 1 and 9 variants), and co-resistance. Percent susceptible was > 99% for plazomicin, meropenem, imipenem, and tigecycline; 96–98% for amikacin and ertapenem; and ≤ 75% for the remaining comparators. For most comparators, MICs varied significantly in relation to multiple bacterial characteristics, in agent-specific patterns. By contrast, for plazomicin, the only bacterial characteristic significantly associated with MICs was ST131 subclone: plazomicin MICs were lowest among O16 ST131 isolates and highest among ST131-H30R1 C1-M27 subclone isolates. Additionally, plazomicin MICs varied significantly in relation to resistance vs. susceptibility to comparator agents only for amikacin and levofloxacin. For most study agents, antimicrobial activity against ESCREC varied extensively in relation to multiple bacterial characteristics, including clonal background, whereas for plazomicin, it varied only by ST131 subclone (C1-M27 isolates least susceptible, O16 isolates most susceptible). These findings support plazomicin as a reliable alternative for treating ESCREC infections and urge continued attention to the C1-M27 ST131 subclone.

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Acknowledgements

The MVAMC Clinical Microbiology Laboratory provided the study isolates.

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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Funding

This work was supported by an investigator-initiated grant from Cipla/Achaogen. This work was also supported by Office of Research and Development, Department of Veterans Affairs and the National Institute of Allergy and Infectious Diseases of the NIH (Antibacterial Resistance Leadership Group, award number UM1AI104681) (JRJ). The sponsors had no role in study design, data collection, data analysis, writing the manuscript, or the decision to publish.

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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, Connie Clabots & James R. Johnson

  2. University of Minnesota, Minneapolis, MN, USA

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

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  1. Brian D. Johnston
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  2. Paul Thuras
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  4. Connie Clabots
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Contributions

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

2. Paul Thuras: Statistical analysis

3. Stephen B. Porter: Isolate collection, data collection, and manuscript editing

4. Connie Clabots: Isolate collection, data collection, and manuscript editing

5. James R. Johnson: Concept, funding, project oversight, and manuscript drafting and editing

Corresponding author

Correspondence to James R. Johnson.

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Ethics approval (include appropriate approvals or waivers): 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. The other authors report no financial conflicts of interest.

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Johnston, B.D., Thuras, P., Porter, S.B. et al. Comparative activity of plazomicin against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012–2017) in relation to phylogenetic background, sequence type 131 subclones, blaCTX-M genotype, and resistance to comparator agents. Eur J Clin Microbiol Infect Dis 40, 2069–2075 (2021). https://doi.org/10.1007/s10096-021-04256-9

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