Indications
Avibactam, when used in combination with ceftazidime (known as AVYCAZ), is indicated for the treatment of specific bacterial infections. In conjunction with metronidazole, it is approved for addressing complicated intra-abdominal infections in patients aged 18 and older, caused by susceptible organisms such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca, and Pseudomonas aeruginosa. Additionally, AVYCAZ is prescribed for the treatment of complicated urinary tract infections, including pyelonephritis, in adults, targeting similar microorganisms.
Pharmacodynamics
Detailed pharmacodynamic data for avibactam is currently not available. However, as a β-lactamase inhibitor, avibactam enhances the efficacy of ceftazidime by protecting it from degradation by β-lactamase enzymes produced by certain bacteria, thereby expanding its antibacterial activity.
Absorption
Information regarding the absorption characteristics of avibactam is not specified. As a component of AVYCAZ, it is administered intravenously, which facilitates direct entry into the systemic circulation, bypassing gastrointestinal absorption processes.
Metabolism
Avibactam remains largely unmetabolized in the human body. Studies with human liver preparations have shown no significant metabolic activity concerning avibactam. The compound is predominantly excreted unchanged, with the majority detected in human plasma and urine. Regarding ceftazidime, 80-90% is eliminated in its unchanged form, also highlighting minimal metabolic alteration post-administration.
Mechanism of Action
Avibactam functions as a non-β lactam β-lactamase inhibitor that effectively neutralizes specific β-lactamases, including Ambler classes A, C, and certain class D enzymes. It achieves this through a distinctive covalent and reversible mechanism. This action safeguards ceftazidime from degradation by certain β-lactamases. Avibactam rapidly permeates into the bacterial periplasm at sufficient concentrations, thereby restoring the efficacy of ceftazidime against strains that are resistant due to β-lactamase production. Importantly, avibactam does not compromise the activity of ceftazidime against organisms that are already susceptible to it.
