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Case Reports
. 2024 Jan 10;68(1):e0100923.
doi: 10.1128/aac.01009-23. Epub 2023 Dec 8.

The emergence of cefiderocol resistance in Pseudomonas aeruginosa from a heteroresistant isolate during prolonged therapy

Nicholas Teran  1 , Stephanie L Egge  2   3 , Kady Phe  1 , Rodrigo P Baptista  2   4 , Vincent H Tam  5 , William R Miller  2   3   4
Affiliations
Case Reports

The emergence of cefiderocol resistance in Pseudomonas aeruginosa from a heteroresistant isolate during prolonged therapy

Nicholas Teran et al. Antimicrob Agents Chemother. .

Abstract

Cefiderocol is a siderophore cephalosporin designed to target multi-drug-resistant Gram-negative bacteria. Previously, the emergence of cefiderocol non-susceptibility has been associated with mutations in the chromosomal cephalosporinase (PDC) along with mutations in the PirA and PiuA/D TonB-dependent receptor pathways. Here, we report a clinical case of cefiderocol-resistant P. aeruginosa that emerged in a patient during treatment. This resistance was associated with mutations not previously reported, suggesting potential novel pathways to cefiderocol resistance.

Keywords: Pseudomonas aeruginosa; cefiderocol; gram-negative bacteria; siderophores.

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Conflict of interest statement

V.H.T. has received consultant fees from Taxis Pharmaceuticals, Inc. W.R.M. has received research support from Merck and royalties from UpToDate. S.L.E., R.P.B., N.T. and K.P.: none to declare.

Figures

Fig 1
Fig 1
Population analysis profiles of sequentially collected multi-drug-resistant P. aeruginosa. Isolate profiles were compared to representative susceptible control (PAO1, open circle) and heteroresistant control (C1814, X) phenotypes. Dash-dot line represents the cutoff for heteroresistance. Error bars represent 95% confidence intervals across triplicate runs with a controlled inoculum of approximately 107–108. P-values for comparison of individual isolate growth relative to PAO1: ns, not significant, * ≤0.05, ** ≤0.01, *** ≤0.001, **** ≤0.0001.
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