The H30 subclone of Escherichia coli sequence type 131 (ST131-H30) has become the leading antimicrobial resistance E. coli lineage in the United States and often exhibits resistance to one or both of the two key antimicrobial classes for treating Gram-negative infections, extended-spectrum cephalosporins (ESCs) and fluoroquinolones (FQs). However, the timing of and reasons for its recent emergence are inadequately defined. Accordingly, from E. coli clinical isolates collected systematically across the United States by the SENTRY Antimicrobial Surveillance Program in 2000, 2003, 2006, and 2009, 234 isolates were selected randomly, stratified by year, within three resistance categories: (i) ESC-reduced susceptibility, regardless of FQ phenotype (ESC-RS); (ii) FQ resistance, ESC susceptible (FQ-R); and (iii) FQ susceptible, ESC susceptible (FQ-S). Susceptibility profiles, phylogroup, ST, ST131 subclone, and virulence genotypes were determined, and temporal trends and between-variable associations were assessed statistically. From 2000 to 2006, concurrently with the emergence of ESC-RS and FQ-R strains, the prevalence of (virulence-associated) phylogroup B2 among such strains also rose dramatically, due entirely to rapid emergence of ST131, especially H30. By 2009, H30 was the dominant E. coli lineage overall (22%), accounting for a median of 43% of all single-agent and multidrug resistance (68% for ciprofloxacin). H30’s emergence increased the net virulence gene content of resistant (especially FQ-R) isolates, giving stable overall virulence gene scores despite an approximately 4-fold expansion of the historically less virulent resistant population. These findings define more precisely the timing and tempo of H30’s emergence in the United States, identify possible reasons for it, and suggest potential consequences, including more frequent and/or aggressive antimicrobial-resistant infections.
Bibliographical noteFunding Information:
This work was supported by merit review award numbers I01 CX000192 01 and I01 CX000920 from the U.S. Department of Veterans Affairs Clinical Sciences R&D (CSRD) Service (both to J.R.J.). The sponsor had no involvement in the conduct of the study, data analysis, manuscript preparation, or decision to publish. J. R. Johnson has received contracts, grants, or consultancies from Actavis, Jannsen, Merck, and Tetraphase and has patent applications pertaining to tests for specific E. coli strains. M. Castanheira is an employee of JMI Laboratories, which was contracted to perform services in 2016 for Achaogen, Actelion, Allecra, Allergan, Ampliphi, API, Astellas, AstraZeneca, Basilea, Bayer, BD, Biomodels, Cardeas, CEM-102 Pharma, Cempra, Cidara, Cormedix, CSA Biotech, Cubist, Debiopharm, Dipexium, Duke, Durata, Entasis, Fortress, Fox Chase Chemical, GSK, Medpace, Melinta, Merck, Micurx, Motif, N8 Medical, Nabriva, Nexcida, Novartis, Paratek, Pfizer, Polyphor, Rempex, Scynexis, Shionogi, Spero Therapeutics, Symbal Therapeutics, Synolgoic, TGV Therapeutics, The Medicines Company, Theravance, Thermo Fisher, VenatoRx, Wockhardt, and Zavante. Additionally, some JMI employees are advisors/consultants for Allergan, Astellas, Cubist, Pfizer, Cempra, and Theravance. The other authors report no conflicts of interest.
© 2017 American Society for Microbiology. All Rights Reserved.
Copyright 2017 Elsevier B.V., All rights reserved.
- Antimicrobial resistance
- Epidemic emergence
- Escherichia coli ST131
- Extended-spectrum beta-lactamases
- Fluoroquinolone resistance
- Molecular epidemiology