Avibactam sodium hydrate (NXL-104 hydrate) is a covalent and reversible inhibitor of β-lactamase that does not contain a β-lactam core. Avibactam sodium hydrate inhibits β-lactamase CTX-M-15 and TEM-1 with IC 50 s of 5 nM and 8 nM, respectively.

Avibactam sodium hydrate (NXL-104 hydrate) is a compound exhibiting minimal antibacterial activity, primarily functioning to inhibit class A and C β-lactamases. However, it is ineffective against metallo-β-lactamases and Acinetobacter OXA carbapenemases [2].

Avibactam sodium hydrate (NXL-104 hydrate) exhibits a gradual restoration of its activity, with a delineated off-rate of 0.045±0.022 min^-1, equating to a residence time half-life (t1/2) of approximately 16±8 minutes. This suggests that Avibactam undergoes slow deacylation through hydrolysis or reversibility, contrasting with its previously cited extended half-life values of greater than 1 or 7 days when inhibiting TEM-1 [1]. As a novel β-lactamase inhibitor, Avibactam shows promise in countering β-lactamase-induced resistance. In experimental models, mice infected with approximately 10^6 CFU of Pseudomonas aeruginosa either intramuscularly in the thigh or intranasally to induce pneumonia receive eight distinct (single) subcutaneous doses of GR20263 and Avibactam in various combinations, with dosage ranging from 1 to 128 mg/kg in two-fold increments. The observed average half-life of GR20263 in plasma during the terminal phase is 0.28 h (SD, 0.02 h), while Avibactam exhibits a half-life of 0.24 h (SD, 0.04 h). The distribution volumes for GR20263 and Avibactam are 0.80 liters/kg (SD, 0.14 liters/kg) and 1.18 liters/kg (SD, 0.34 liters/kg), respectively [3].