Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa

作者：Mustafa Sadek, Rémi Le Guern, Éric Kipnis, Philippe Gosset, Laurent Poirel, Rodrigue Dessein, Patrice Nordmann · 发表于：European Journal of Clinical Microbiology & Infectious Diseases · 年份：2022 · DOI：10.1007/s10096-022-04526-0 · 被引用次数：38 · 研究领域：Antibiotic Resistance in Bacteria、Bacterial biofilms and quorum sensing、Antibiotic Use and Resistance

We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas 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 recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. 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-lactamase 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, and mexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription.