Avibactam free acid is a potent β-lactamase inhibitor exhibiting covalent and reversible properties, capable of inhibiting TEM-1, P99, and CTX-M-15 at nanomolar concentrations. Avibactam free acid and Ceftazidime may be combined for treating urinary tract infections.

CTX-M-15:5 nM, TEM1:8 nM

Using TEM-1 as the research subject, the inhibitory effect of Avibactam free acid was characterized by measuring the on-rate (acylation) and off-rate (deacylation) of the enzyme. The results showed that the deacylation dissociation rate was 0.045 min⁻¹, providing potential insights into the deacylation pathway of TEM-1 enzyme. Using nuclear magnetic resonance (NMR) and mass spectrometry (MS), we discovered that the deacylation process regenerates intact Avibactam free acid rather than proceeding via hydrolysis [1].

In the mouse model infected with Klebsiella pneumoniae strain Y8, Ceftazidime-Avibactam free acid (0.375 mg/g, subcutaneous injection, every 8 hours for 10 days) exhibited significant antibacterial effects and produced certain therapeutic outcomes [3].
In the neutropenic pneumonia mouse model with Pseudomonas aeruginosa infection, following a single subcutaneous injection of Avibactam free acid (64 mg/kg), the mean estimated terminal-phase half-life in mouse plasma was 0.24 hours [3].