Objectives: Cefiderocol maintains activity against most MDR Gram-negative pathogens including Pseudomonas aeruginosa. In laboratory-derived isolates, down-regulation of TonB-dependent siderophore receptors have been implicated in resistance to cefiderocol.
Methods: In this report, the expression of seven TonB-dependent siderophore receptors was examined in 10 clinical isolates with cefiderocol MICs ranging from ≤0.03-8 mg/L. In addition, genetic sequences of the siderophore receptors were analysed to identify potentially disruptive mutations.
Results: There was no clear association between expression of the receptors with cefiderocol susceptibility, including the receptors piuA/piuD and pirA previously implicated in cefiderocol uptake. In addition, there were no disabling mutations identified in the receptors. Acquired β-lactamase activity also could not explain the range in cefiderocol susceptibility.
Conclusions: The aetiology of reduced susceptibility to cefiderocol in clinical isolates of P. aeruginosa remains an enigma and worthy of further investigation.
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