Resistance to ceftazidime/avibactam plus meropenem/vaborbactam when both are used together is achieved in four steps in metallo-β-lactamase-negative Klebsiella pneumoniae

Punyawee Dulyayangkul, Ed Douglas, Filip Lastovka, Matthew Avison

Research output: Contribution to journalArticlepeer-review

Abstract

Meropenem-vaborbactam resistance in Klebsiella pneumoniae isolates is associated with loss-of-function mutations in the OmpK35 and OmpK36 porins. We identify two previously unknown loss-of-function mutations that confer cefuroxime resistance in K. pneumoniae isolates. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor that controls capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem-vaborbactam in a KPC-3-producing K. pneumoniae isolate.
Original languageEnglish
Article numbere02208-19
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number7
Early online date23 Jun 2020
DOIs
Publication statusPublished - 23 Jun 2020

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