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Activity of the novel siderophore cephalosporin cefiderocol against multidrug-resistant Gram-negative pathogens

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Abstract

The novel siderophore cephalosporin cefiderocol (S-649266) with potent activity against Gram-negative pathogens was recently developed (Shionogi & Co., Ltd.). Here, we evaluated the activity of this new molecule and comparators against a collection of previously characterized Gram-negative isolates using broth microdilution panels. A total of 753 clinical multidrug-resistant Gram-negative isolates collected from hospitals worldwide were tested against cefiderocol and antibiotic comparators (ceftolozane–tazobactam [CT], meropenem [MEM], ceftazidime [CAZ], ceftazidime–avibactam [CZA], colistin [CST], aztreonam [ATM], amikacin [AMK], ciprofloxacin [CIP], cefepime [FEP], and tigecycline [TGC]) for their susceptibility. The collection included Escherichia coli (n = 164), Klebsiella pneumoniae (n = 298), Enterobacter sp. (n = 159), Pseudomonas aeruginosa (n = 45), and Acinetobacter baumannii (n = 87). Resistance mechanisms included producers of carbapenemases and extended-spectrum β-lactamases (ESBLs). In addition, a series of colistin-resistant enterobacterial isolates (n = 74), including 15 MCR-1 producers, were tested. The MIC90 of cefiderocol was 2 mg/L, while those of comparative drugs were >64 mg/L for CT, MEM, CAZ, CZA, and AMK, >32 mg/L for ATM, >16 mg/L for FEP, 8 mg/L for CST, and 2 mg/L for TGC. The MIC50 of cefiderocol was 0.5 mg/L, while those of other drugs were >64 mg/L for CAZ, 64 mg/L for CT, >32 mg/L for ATM, >16 mg/L for FEP, 8 mg/L for MEM and AMK, >4 mg/L for CIP, 1 mg/L for CZA, 0.5 mg/L for TGC, and <0.5 mg/L for CST. Only 20 out of 753 strains showed MIC values of cefiderocol ≥8 μg/mL. Compared to the other drugs tested, cefiderocol was more active, with the exception of colistin and tigecycline showing equivalent activity against certain subgroups of bacteria.

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Authors and Affiliations

  1. Emerging Antibiotic Resistance Unit, University of Fribourg, Fribourg, Switzerland

    J. Dobias, V. Dénervaud-Tendon, L. Poirel & P. Nordmann

  2. National Reference Center for Emerging Antibiotic Resistance (Switzerland), University of Fribourg, Fribourg, Switzerland

    J. Dobias, V. Dénervaud-Tendon, L. Poirel & P. Nordmann

  3. French INSERM European Unit (LEA/IAME), University of Fribourg, Fribourg, Switzerland

    J. Dobias, V. Dénervaud-Tendon, L. Poirel & P. Nordmann

  4. Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, rue Albert Gockel 3, 1700, Fribourg, Switzerland

    J. Dobias, V. Dénervaud-Tendon, L. Poirel & P. Nordmann

  5. Institute for Microbiology, University of Lausanne and University Hospital Centre, Lausanne, Switzerland

    P. Nordmann

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  1. J. Dobias
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  2. V. Dénervaud-Tendon
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  3. L. Poirel
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  4. P. Nordmann
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Correspondence to P. Nordmann.

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This work was funded by grants from the University of Fribourg and from Shionogi & Co., Ltd.

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Dobias, J., Dénervaud-Tendon, V., Poirel, L. et al. Activity of the novel siderophore cephalosporin cefiderocol against multidrug-resistant Gram-negative pathogens. Eur J Clin Microbiol Infect Dis 36, 2319–2327 (2017). https://doi.org/10.1007/s10096-017-3063-z

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  • DOI: https://doi.org/10.1007/s10096-017-3063-z

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