2. Academic Validation
  3. In-vitro activity of newly-developed β-lactamase inhibitors avibactam, relebactam and vaborbactam in combination with anti-pseudomonal β-lactam antibiotics against AmpC-overproducing clinical Pseudomonas aeruginosa isolates

In-vitro activity of newly-developed β-lactamase inhibitors avibactam, relebactam and vaborbactam in combination with anti-pseudomonal β-lactam antibiotics against AmpC-overproducing clinical Pseudomonas aeruginosa isolates

  • Eur J Clin Microbiol Infect Dis. 2024 Nov 26. doi: 10.1007/s10096-024-04965-x.
Christophe Le Terrier 1 2,  Otávio Hallal Ferreira Raro 1,  Alaaeldin Mohamed Saad 1 3,  Patrice Nordmann 1 4,  Laurent Poirel 5 6
Affiliations

Affiliations

  • 1 Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Chemin du Musée 18, Fribourg, CH-1700, Switzerland.
  • 2 Division of Intensive Care Unit, University Hospitals of Geneva, Geneva, Switzerland.
  • 3 Department of Zoonoses, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
  • 4 Swiss National Reference Center for Emerging Antibiotic Resistance, Fribourg, Switzerland.
  • 5 Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Chemin du Musée 18, Fribourg, CH-1700, Switzerland. laurent.poirel@unifr.ch.
  • 6 Swiss National Reference Center for Emerging Antibiotic Resistance, Fribourg, Switzerland. laurent.poirel@unifr.ch.
PMID: 39589655 DOI: 10.1007/s10096-024-04965-x
Abstract

Purpose: Overproduction of the intrinsic chromosomally-encoded AmpC β-lactamase is one of the main mechanisms responsible for broad-spectrum β-lactam resistance in Pseudomonas aeruginosa. Our study aimed to evaluate the in-vitro activity of anti-pseudomonal β-lactam molecules associated with the recently-developed and commercially-available β-lactamase inhibitors, namely avibactam, relebactam and vaborbactam, against P. aeruginosa isolates overproducing their AmpC.

Methods: MIC values of ceftazidime, cefepime, meropenem, imipenem and ceftolozane with or without β-lactam Inhibitor were determined for 50 AmpC-overproducing P. aeruginosa clinical isolates. MIC breakpoints for resistance were retained at 8 mg/L for β-lactams and β-lactam/β-lactamase inhibitor combinations containing ceftazidime, cefepime and meropenem, while 4 mg/L was used for those containing imipenem and ceftolozane. The concentration of all β-lactamases inhibitors was fixed at 4 mg/L, except for vaborbactam (8 mg/L).

Results: The rates of isolates not being resistant to ceftazidime, cefepime, meropenem, imipenem and ceftolozane were found at 12%, 22%, 34%, 8% and 74%, respectively. When combined with avibactam, those rates increased to 60%, 62%, 60%, 46%, and 80%, respectively. The highest rates were found with relebactam-based combinations, being 76%, 64%, 66%, 76% and 84%, respectively. By contrast, associations with vaborbactam did not lead to significantly increased "non-resistance" rates.

Conclusion: Our results showed that all combinations including relebactam led to higher "non-resistance" rates against AmpC-overproducing P. aeruginosa clinical isolates. The best activity was achieved by combining ceftolozane and relebactam, that might therefore be considered as an excellent clinical alternative against AmpC overproducers.

Keywords

Pseudomonas aeruginosa; AmpC overproducing; Antimicrobial resistance; Avibactam; Carbapenem; Ceftolozane; Cephalosporins; Relebactam; Vaborbactam; β-lactamases inhibitors.

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