Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa
We report in vivo development of cefiderocol (FDC) resistance among four sequentialPseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recoveredP. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-typeP. aeruginosa (0.12 –0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively). Those isolates also showed variable and gradual increasing levels of resistance to most β-lactams tested in this study. Surprisingly, no acquired β-la ctamase was identified in any of those isolates. Whole-genome sequence analysis suggested that this resistance was driven by multifactorial mechanisms including mutational changes in iron transporter proteins associated with FDC uptake,ampC gene overproduction, andmexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription.