Interactions between Avibactam and Ceftazidime-Hydrolyzing Class D β-Lactamases
Jean-Marie Frère,
Pierre Bogaerts,
Te-Din Huang,
Patrick Stefanic,
Joël Moray,
Fabrice Bouillenne,
Alain Brans
Affiliations
Jean-Marie Frère
Centre for Protein Engineering, University of Liège, B 4000 Liège, Belgium
Pierre Bogaerts
National Reference Laboratory for Monitoring of Antimicrobial Resistance in Gram-Negative Bacteria, CHU Dinant-Godinne, UCL Namur, B 5530 Yvoir, Belgium
Te-Din Huang
National Reference Laboratory for Monitoring of Antimicrobial Resistance in Gram-Negative Bacteria, CHU Dinant-Godinne, UCL Namur, B 5530 Yvoir, Belgium
Patrick Stefanic
Centre for Protein Engineering, University of Liège, B 4000 Liège, Belgium
Joël Moray
Centre for Protein Engineering, University of Liège, B 4000 Liège, Belgium
Fabrice Bouillenne
Centre for Protein Engineering, University of Liège, B 4000 Liège, Belgium
Alain Brans
Centre for Protein Engineering, University of Liège, B 4000 Liège, Belgium
Class D β-lactamases exhibit very heterogeneous hydrolysis activity spectra against the various types of clinically useful β-lactams. Similarly, and according to the available data, their sensitivities to inactivation by avibactam can vary by a factor of more than 100. In this paper, we performed a detailed kinetic study of the interactions between two ceftazidime-hydrolyzing OXA enzymes and showed that they were significantly more susceptible to avibactam than several other class D enzymes that do not hydrolyze ceftazidime. From a clinical point of view, this result is rather interesting if one considers that avibactam is often administered in combination with ceftazidime.
