Predicting β-lactam resistance using whole genome sequencing in Klebsiella pneumoniae: the challenge of β-lactamase inhibitors. Academic Article uri icon

Overview

abstract

  • Although multiple antimicrobial resistance (AMR) determinants can confer the same in vitro antimicrobial susceptibility testing (AST) phenotype, their differing effect on optimal therapeutic choices is uncertain. Using a large population-based collection of clinical strains spanning a 3.5-year period, we applied WGS to detect inhibitor resistant (IR), extended-spectrum β-lactamase (ESBL), and carbapenem resistant (CR) β-lactamase (bla) genes and compared the genotype to the AST phenotype in select isolates. All blaNDM-1 (9/9) and the majority of blaNDM-1/OXA-48 (3/4) containing isolates were resistant to CAZ/AVI as predicted by WGS. The combination of ATM and CAZ/AVI restored susceptibility by disk diffusion assay. Unexpectedly, clinical Kp isolates bearing blaKPC-8 (V240G) and blaKPC-14 (G242 and T243 deletion) did not test fully resistant to CAZ/AVI. Lastly, despite the complexity of the β-lactamase background, CAZ/AVI retained potency. Presumed phenotypes conferred by AMR determinants need to be tested if therapeutic decisions are being guided by their presence or absence.

publication date

  • July 25, 2020

Research

keywords

  • Anti-Bacterial Agents
  • Klebsiella pneumoniae
  • beta-Lactamase Inhibitors
  • beta-Lactams

Identity

PubMed Central ID

  • PMC8519184

Scopus Document Identifier

  • 85089725456

Digital Object Identifier (DOI)

  • 10.1093/cid/ciz1155

PubMed ID

  • 32858260

Additional Document Info

volume

  • 98

issue

  • 3