Temporal Dynamics of Genetically Heterogeneous Extended-Spectrum Cephalosporin ResistantEscherichia coliBloodstream Infections

Abstract

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. BlaCTX-M variants accounted for most beta-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R Ec-BSIs), and amplification of blaCTX-M genes was widely detected in ESC-R Ec-BSI strains, particularly in carbapenem non-susceptible strains and in strains causing recurrent BSIs. BlaCTX-M-55 was significantly enriched within phylogroup A strains, and we identified blaCTX-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.

A high-resolution genomic and phenotypic analysis of resistance evolution of an Escherichia coli strain from a critical care patient treated with piperacillin/tazobactam.

“…The importance of improving phenotypic-based AST, biochemical assays and utilising predictions from genomic data is highlighted by the TZP-R/3GC-S phenotype presented in this study, and the need to account for gene copy number and predicted expression levels when predicting resistance to BL/BLI combinations. Scores for BL/BLI resistance prediction from genomic data have been developed (72) in addition to β-lactamase copy number calculators (73) and tools like these will be vital to support decisions for use of new BL/BLI combinations and ensure their future efficacy is safeguarded. Alternative diagnostic methods, based on protein detection, such as matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) technology, may provide an alternative strategy to rapidly detect β-lactamase hyperproduction (74).…”