Investigation of cefiderocol resistance prevalence and resistance mechanisms in carbapenem-resistant Pseudomonas aeruginosa, Germany 2019-21

BACKGROUND: Cefiderocol, a novel siderophore cephalosporin, is a promising therapeutic option for infections caused by multidrug-resistant Pseudomonas aeruginosa. We evaluated the activity of cefiderocol against carbapenem-resistant P. aeruginosa (Cr-Pa) isolates and investigated the potential mechanisms involved in resistance. METHODS: 108 CR-Pa isolates collected from patients without prior exposure to the substance were studied. MICs of cefiderocol were determined by broth microdilution using iron-depleted cation-adjusted Mueller-Hinton broth. Whole genome sequencing was performed to investigate the potential resistance mechanisms by comparing resistant and susceptible P. aeruginosa isolates and identifying unique mutations in the resistant group. RESULTS: Of the 108 isolates, nine were resistant to cefiderocol with MIC values ranging from 4 to 32 mg/L. The genetic analysis revealed a broad spectrum of mutations in the resistant isolates associated with iron uptake systems, efflux pumps, AmpC

• Kocer, K.
• Boutin, S.
• Moll, M.
• Nurjadi, D.