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

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.