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

  • Dobias J Emerging Antibiotic Resistance Unit, University of Fribourg, Fribourg, Switzerland.
  • Dénervaud-Tendon V Emerging Antibiotic Resistance Unit, University of Fribourg, Fribourg, Switzerland.
  • Poirel L Emerging Antibiotic Resistance Unit, University of Fribourg, Fribourg, Switzerland.
  • Nordmann P Emerging Antibiotic Resistance Unit, University of Fribourg, Fribourg, Switzerland. patrice.nordmann@unifr.ch.
  • 2017-07-28
Published in:
  • European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. - 2017
Cephalosporins
Dose-Response Relationship, Drug
Drug Resistance, Multiple, Bacterial
Gram-Negative Bacteria
Gram-Negative Bacterial Infections
Humans
Microbial Sensitivity Tests
English 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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  • English
Open access status
green
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https://sonar.ch/global/documents/93765
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