Resistance to Ceftazidime/Avibactam Plus Meropenem/Vaborbactam When Both are Used Together Achieved in Four Steps from Metallo-β-Lactamase Negative Klebsiella pneumoniae.

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Resistance to Ceftazidime/Avibactam Plus Meropenem/Vaborbactam When Both are Used Together Achieved in Four Steps from Metallo-β-Lactamase Negative Klebsiella pneumoniae.

Antimicrob Agents Chemother. 2020 Jul 13;:

Authors: Dulyayangkul P, Douglas EJA, Lastovka F, Avison MB

Abstract
Serine β-lactamases are dominant causes of β-lactam resistance in Klebsiella pneumoniae Recently, this has driven clinical deployment of the β-lactam/β-lactamase inhibitor pairs ceftazidime/avibactam and meropenem/vaborbactam. We show that four steps: 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.

PMID: 32660988 [PubMed - as supplied by publisher]