Genetic determinants underlying the progressive phenotype of β-lactam/β-lactamase inhibitor resistance in < em > Escherichia coli < /em >

Microbiol Spectr. 2023 Oct 6:e0222123. doi: 10.1128/spectrum.02221-23. Online ahead of print.ABSTRACTCurrently, 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 blaTEM 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 blaTEM in ESRI, 112/134 strains (84%) with at least ampicillin non-susceptibility encoded blaTEM. Evidence of blaTEM amplification (i.e., blaTEM gene copy number estimates > 2×) was present in 40/112 (36%) strains. There were positive correlations between blaTEM 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 blaCTX-M variants, ...
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research