<i>In Vitro</i> Activity of Cefiderocol Against Carbapenem-Resistant <i>Enterobacterales</i> and <i>Pseudomonas aeruginosa</i>

Abstract

The objective of this study was to assess the susceptibility of cefiderocol against multidrug-resistant carbapenemase-producing and nonproducing bacteria. The panel comprised 182 isolates of the order Enterobacterales , and 40 strains of Pseudomonas aeruginosa . Antimicrobial susceptibility testing has been performed using broth microdilution method according to the European Committee on Antimicrobial Susceptibility Testing recommendations. Mass spectrometry matrix-assisted laser desorption/ionization-time of flight mass spectrometry and carbapenemase-producing test were used to verify the presence of carbapenemases in clinical isolates. The genetic expression of single carbapenemases ( bla KPC , bla OXA-48 , bla NDM , bla VIM , bla IMP , bla GES ) was determined by real-time polymerase chain reaction. Cefiderocol exhibited a good activity against the majority of strains tested in this study. Altogether, growth of 81.9% ( n = 149) strains of the order Enterobacterales and 77.5% ( n = 31) of P. aeruginosa isolates were inhibited at minimal inhibitory concentration (MIC) ≤2 mg/L. Values MIC 50 /MIC 90 were 0.5/8 mg/L for enterobacteria, and 1/8 mg/L for P. aeruginosa . One isolate ( Klebsiella pneumoniae ) harboring two carbapenemases ( bla OXA-48 , bla NDM ) had cefiderocol MIC 0.5 mg/L. In enterobacteria resistant to cefiderocol, bla NDM carbapenemase prevailed (43.3%, n = 29), followed by bla OXA-48 (31.3%, n = 21) and bla KPC (4.5%, n = 3). bla IMP ( n = 8) and bl a VIM ( n = 1) metallo-β-lactamases dominated in cefiderocol-resistant P. aeruginosa ( n = 9) isolates. Very good susceptibility (100%) to this drug showed bla GES -positive strains of P. aeruginosa ( n = 8) and isolates resistant to meropenem without confirmed carbapenemase gene ( n = 10). In this study, cefiderocol demonstrated potent activity against important nosocomial pathogens, therefore, therapeutic options of this drug against multidrug-resistant bacteria should be considered.