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Extended-spectrum cephalosporin resistant (ESC-R) Escherichia coli (ESC-R- Ec ) is an urgent public health threat with clonal complex (CC) 131, phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R- Ec infections. To address the paucity of recent ESC-R- Ec molecular epidemiology data in the United States (US), we used whole genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R- Ec at a tertiary care cancer center in Houston, Texas collected from 2016-2020. During the study timeframe, there were 1154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R. Using time series analyses, we identified a temporal dynamic of ESC-R E. coli BSIs ( Ec -BSIs), distinct from ESC-susceptible Ec -BSIs, with cases peaking in the last 6 months of the calendar year. WGS of 297 ESC-R Ec -BSI strains revealed that while CC131 strains accounted for ∼45% of total infections, the proportion of CC131 strains remained stable across the time-period, and infection peaks were driven by genetically diverse, non-CC131 isolates. Bla (CTX-M) variants accounted for most β-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R Ec -BSIs), and amplification of bla (CTX-M) genes was widely detected in ESC-R Ec -BSI strains, particularly in carbapenem non-susceptible strains and in strains causing recurrent BSIs. Bla (CTX- M-55) was significantly enriched within phylogroup A strains, and we identified bla (CTX-M-55) plasmid-to-chromosome transmission occurring across non-B2 strains. Our data provide important information regarding the current molecular epidemiology of invasive ESC-R E. coli and provide novel insights into the genetic basis of observed temporal variability for these clinically important pathogens. IMPORTANCE: Given that E. coli is the leading cause of ESC-R Enterobacterales infection, we sought to assess the current molecular epidemiology of ESC-R- Ec using a WGS based analysis of many BSIs over a several year period. We identified a clear temporal dynamic of ESC-R- Ec infections, which has also recently been identified in other geographical regions such as Israel. Our WGS data allowed us to visualize the stable nature of CC131 over the study period and demonstrate that non-CC131 strains drove the infection peaks. Additionally, we provide the first widespread assessment of β-lactamase gene copy number in ESC-R- Ec infections and delineate mechanisms by which such amplifications are achieved in a diverse array of ESC-R- Ec strains. These data suggest that even for a tertiary care center, serious ESC-R- Ec infections are driven by a diverse array of strains and impacted by environmental factors suggesting that community-based monitoring could inform novel preventative measures. |
