Year: 2022
Type: article
Abstract: 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.
Institutions: University of Fribourg, South Valley University, Centre National de la Recherche Scientifique, Inserm, Université de Lille, Institut Pasteur de Lille, Centre Hospitalier Universitaire de Lille, Center for Infection and Immunity of Lille, Institut Pasteur, Centre Hospitalier Universitaire Vaudois, University of Lausanne
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,190
OpenAlex ID: W4308986769