Faculty, Staff and Student Publications
Publication Date
12-12-2023
Journal
Microbiology Spectrum
Abstract
Currently, whole-genome sequencing (WGS) data have not shown strong concordance with Escherichia coli susceptibility profiles to the commonly used β-lactam/β-lactamase inhibitor (BL/BLI) combinations: ampicillin-sulbactam (SAM), amoxicillin-clavulanate (AMC), and piperacillin-tazobactam (TZP). Progressive resistance to these BL/BLIs in the absence of cephalosporin resistance, also known as extended-spectrum resistance to BL/BLI (ESRI), has been suggested to primarily result from increased copy numbers of bla TEM variants, which is not routinely assessed in WGS data. We sought to determine whether addition of gene amplification could improve genotype-phenotype associations through WGS analysis of 147 E. coli bacteremia isolates with increasing categories of BL/BLI non-susceptibility ranging from ampicillin (AMP) susceptibility to being fully resistant to all three BL/BLIs. Consistent with a key role of bla TEM in ESRI, 112/134 strains (84%) with at least ampicillin non-susceptibility encoded bla TEM. Evidence of bla TEM amplification (i.e., bla TEM gene copy number estimates > 2×) was present in 40/112 (36%) strains. There were positive correlations between bla TEM copy numbers with minimum inhibitory concentrations of AMC and TZP (P < 0.05) but not for SAM (P = 0.09). The diversity of β-lactam resistance mechanisms, including non-ceftriaxone hydrolyzing bla CTX-M variants, bla OXA-1, and ampC and bla TEM strong promoter mutations, was greater in AMC- and TZP-non-susceptible strains but rarely observed within SAM- and AMP-non-susceptible isolates. Our study indicates that comprehensive analysis of WGS data, including β-lactamase-encoding gene amplification, can help categorize E. coli with AMC or TZP non-susceptibility but that discerning the transition from SAM susceptibility to SAM non-susceptibility using genetic data requires further refinement.
Keywords
Humans, beta-Lactamase Inhibitors, Escherichia coli, Anti-Bacterial Agents, Lactams, Escherichia coli Infections, Phenotype, beta-Lactams, Monobactams, beta-Lactamases, Microbial Sensitivity Tests, ESRI, progressive AMR resistance, BL/BLI, AMR gene amplification
Included in
Bioinformatics Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Genomics Commons, Medical Genetics Commons, Molecular Genetics Commons, Oncology Commons
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Associated Data
PMID: 37800937