AmpC β-lactamase induction by avibactam and relebactam

Area of Science:

• Microbiology
• Pharmacology
• Molecular Biology

Background:

• Diazabicyclooctanes, including avibactam and relebactam, are novel beta-lactamase inhibitors.
• Their inhibitory spectrum encompasses AmpC enzymes, necessitating an investigation into their potential to induce these enzymes.

Purpose of the Study:

• To determine if avibactam and relebactam induce AmpC enzymes in key bacterial species.
• To compare the induction potential of these novel inhibitors with cefoxitin.

Main Methods:

• AmpC mRNA levels were quantified using RT-PCR in Enterobacter cloacae, Citrobacter freundii, and Pseudomonas aeruginosa exposed to avibactam, relebactam, and cefoxitin.
• Induction was defined as significant if induction ratios exceeded 10 at two consecutive time points, with strong induction >100.

Main Results:

• Cefoxitin induced AmpC in all strains concentration-dependently.
• Relebactam did not induce significant AmpC expression in any tested strain.
• Avibactam exhibited variable AmpC induction, with strong induction observed in some strains of E. cloacae and P. aeruginosa.

Conclusions:

• Avibactam possesses a strain-variable capacity to induce AmpC enzymes.
• Relebactam does not induce AmpC enzymes.
• Observed induction by avibactam occurred at concentrations exceeding therapeutic levels.