In vitro development of imipenem/relebactam resistance in KPC-producing Klebsiella pneumoniae involves multiple mutations including OmpK36 disruption and KPC modification.

Objectives: In order to inform and anticipate potential strategies aimed at combating KPC-producing Klebsiella pneumoniae infections, we analysed imipenem/relebactam and ceftazidime/avibactam single-step mutant frequencies, resistance development trajectories, differentially selected resistance mechanisms and their associated fitness cost using four representative high-risk K. pneumoniae clones.

Methods: Mutant frequencies and mutant preventive concentrations were determined using agar plates containing incremental concentrations of β-lactam/β-lactamase inhibitor.

Antimicrobial Activity of Cefiderocol against the Carbapenemase-Producing Enterobacter cloacae Complex and Characterization of Reduced Susceptibility Associated with Metallo-β-Lactamase VIM-1.

Emergence of cefiderocol resistance among carbapenemase-producing Enterobacterales, particularly those in the Enterobacter cloacae complex (ECC), is becoming of alarming concern; however, the mechanistic basis of this phenomenon remains poorly understood. We describe the acquisition of VIM-1-mediated reduced cefiderocol susceptibility (MICs 0.5 to 4 mg/L) in a collection of 54 carbapenemase-producing isolates belonging to the ECC.

Activity of aztreonam in combination with novel β-lactamase inhibitors against metallo-β-lactamase-producing Enterobacterales from Spain.

Metallo-β-lactamase (MBL)-producing Enterobacterales are of particular concern because they are widely disseminated and difficult to treat, being resistant to almost all β-lactam antibiotics. Aztreonam is not hydrolysed by MBLs but is labile to serine β-lactamases (SBLs), which are usually co-produced by MBL-producing Enterobacterales. This study investigated the activity of aztreonam in combination with novel β-lactamase inhibitors (BLIs) against a national multi-centre study collection of strains co-producing MBLs and SBLs.