Klebsiella pneumoniae mutants resistant to ceftazidime/avibactam plus aztreonam, imipenem/relebactam, meropenem/vaborbactam and cefepime/taniborbactam

Abstract

Using modified Klebsiella pneumoniae clinical isolates, we show that ramR plus ompK36 mutation together with production of the V239G variant KPC-3 confirs resistance to ceftazidime/avibactam plus aztreonam, imipenem/relebactam and meropenem/vaborbactam, but not cefepime/taniborbactam. This is because the V239G variant does not generate collateral β-lactam susceptibility as do many other KPC-3 variants associated with ceftazidime/avibactam resistance. Additional mutation of ompK35 and carriage of a plasmid expressing the OXA-48-like carbapenemase OXA-232 was required to confer cefepime/taniborbactam resistance.