In Vitro Activity of Cefiderocol Against Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa
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 bla(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.