1. Academic Validation
  2. Resistance to Ceftazidime/Avibactam plus Meropenem/Vaborbactam When Both Are Used Together Is Achieved in Four Steps in Metallo-β-Lactamase-Negative Klebsiella pneumoniae

Resistance to Ceftazidime/Avibactam plus Meropenem/Vaborbactam When Both Are Used Together Is Achieved in Four Steps in Metallo-β-Lactamase-Negative Klebsiella pneumoniae

  • Antimicrob Agents Chemother. 2020 Sep 21;64(10):e00409-20. doi: 10.1128/AAC.00409-20.
Punyawee Dulyayangkul  # 1 Edward J A Douglas  # 1 Filip Lastovka 1 Matthew B Avison 2
Affiliations

Affiliations

  • 1 School of Cellular & Molecular Medicine, University of Bristol, Bristol, United Kingdom.
  • 2 School of Cellular & Molecular Medicine, University of Bristol, Bristol, United Kingdom bimba@bris.ac.uk.
  • # Contributed equally.
Abstract

Serine β-lactamases are dominant causes of β-lactam resistance in Klebsiella pneumoniae isolates. Recently, this has driven clinical deployment of the β-lactam-β-lactamase inhibitor pairs ceftazidime/avibactam and meropenem/vaborbactam. We show that four steps, i.e., ompK36 and ramR mutation plus carriage of OXA-232 and KPC-3-D178Y variant β-lactamases, confer ceftazidime/avibactam and meropenem/vaborbactam resistance when both pairs are used together. These findings have implications for decision making about sequential and combinatorial use of these β-lactam-β-lactamase inhibitor pairs to treat K. pneumoniae infections.

Keywords

KPC; OXA-48; porin; β-lactamase.

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