4.7 Article

Klebsiella pneumoniae Mutants Resistant to Ceftazidime-Avibactam Plus Aztreonam, Imipenem-Relebactam, Meropenem-Vaborbactam, and Cefepime-Taniborbactam

Journal

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 66, Issue 4, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/aac.02179-21

Keywords

KPC; carbapenemase

Funding

  1. Antimicrobial Resistance Cross Council Initiative [MR/S004769/1]
  2. National Institute for Health Research
  3. University of Bristol

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The study reveals a variant of Klebsiella pneumoniae that exhibits resistance to multiple antibiotics, including ceftazidime-avibactam and meropenem-vaborbactam. Further mutations and enzyme production are required for resistance to other antibiotics.
We show that a previously described Klebsiella pneumoniae variant that is resistant to ceftazidime-avibactam plus meropenem-vaborbactam, has a ramR plus ompK36 mutation, and produces the V239G variant KPC-3 (V240G per the standard numbering system) exhibits resistance to ceftazidime-avibactam plus aztreonam and imipenem-relebactam but not cefepime-taniborbactam. The V239G variant does not generate collateral beta-lactam susceptibility like many KPC-3 variants associated with ceftazidime-avibactam resistance. Additional mutation of ompK35 and production of the OXA-48-like carbapenemase OXA-232 were required to confer cefepime-taniborbactam resistance.

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