Predicting β-lactam resistance using whole genome sequencing in Klebsiella pneumoniae: the challenge of β-lactamase inhibitors

Andrea M. Hujer, S. Wesley Long, Randall J. Olsen, Magdalena A. Taracila, Laura J. Rojas, James M. Musser, Robert A. Bonomo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number115149
JournalDiagnostic Microbiology and Infectious Disease
Volume98
Issue number3
DOIs
StatePublished - Nov 2020

Keywords

  • Avibactam
  • Aztreonam
  • Ceftolozane
  • Klebsiella pneumoniae
  • beta-Lactamase inhibitors

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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