Acquisition of Extended-Spectrum β-Lactamase GES-6 Leading to Resistance to Ceftolozane-Tazobactam Combination in Pseudomonas aeruginosa

  • Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01809-18. doi: 10.1128/AAC.01809-18.
Laurent Poirel  1  2  3 ,  José-Manuel Ortiz De La Rosa  4  2 ,  Nicolas Kieffer  4  3 ,  Véronique Dubois  5  6 ,  Aurélie Jayol  4  2  3  7 ,  Patrice Nordmann  4  2  3  8
Affiliations
  • 1. Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland [email protected].
  • 2. INSERM European Unit (LEA), IAME, Paris, France.
  • 3. Swiss National Reference Center for Emerging Antibiotic Resistance, Fribourg, Switzerland.
  • 4. Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
  • 5. Laboratory of Bacteriology, Bordeaux University Hospital, Bordeaux, France.
  • 6. CNRS UMR5234, University of Bordeaux, Bordeaux, France.
  • 7. Laboratory of Microbiology, Hospital Yverdon, Yverdon-les-Bains, Switzerland.
  • 8. University of Lausanne and University Hospital Center, Lausanne, Switzerland.
PMID: 30323045 DOI: 10.1128/AAC.01809-18
Abstract

A clinical Pseudomonas aeruginosa isolate resistant to all β-lactams, including ceftolozane-tazobactam and carbapenems, was recovered. It belonged to sequence type 235 and produced the extended-spectrum β-lactamase (ESBL) GES-6 differing from GES-1 by two amino acid substitutions (E104K and G170S). GES-6 possessed an increased hydrolytic activity toward carbapenems and to ceftolozane and a decreased susceptibility to β-lactamase inhibitors compared to GES-1, except for avibactam. We show here that resistance to ceftolozane-tazobactam may occur through acquisition of a specific ESBL in P. aeruginosa but that ceftazidime-avibactam combination remains an effective alternative.

Keywords
ESBL; GES-6; Pseudomonas aeruginosa; ceftolozane-tazobactam.
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