• Penicillins And others

  • Beta-lactamase inhibitors

    • Avibactam

      • Avibactam

      • Mechanism of Action

        • Avibactam representative substantial change in beta-lactamase inhibitor design.

        • This agent is a non-beta-lactamase inhibitor that exhibits a covalent, slowly reversible bond with beta-lactamases, with a deacylation rate of 0.045/min, i.e. about 4.5%/min^1,5

          • The slowly reversible bond with beta-lactamases allows for sustained inhibition since the process regenerates intact inhibitor, allowing avibactam to reform its ring structure and bind again to another target lactamase.^5,6 

        • The reversible covalent mechanism add this to drug potency and enhances the spectrum of activity.

        • Avibactam is a potent inhibitor of Ambler Class A (including ESBLs [extended-spectrum beta-lactamases] and KPC [Klebsiella pneumoniae carbapenemase], Class C enzymes (AmpC),as well as some class D enzymes including OXA-48 carbapenemases.

          • Avibactam-mediated inhibition of both KPC and OXA-48 enhances its clinical importance targeting many carbapenem-resistance Enterobacterales (CRE, Carbapenem-resistant Enterobacterales).

          • However, avibactam does not exhibit activity against Class B metallo-beta-lactamases (MBLs).^3,4

      • Pharmacokinetics

        • Absorption

          • Avibactam uses the intravenous route of administration (IV).⁷

        • Distribution

          • Avibactam exhibits very low plasma protein binding (5.7%-8.2%) with the volume of distribution of about 22 L.^{7, 8}

        • Metabolism

          • Avibactam does not exhibit notable metabolism in humans.

            • Avibactam is eliminated from the body as the unchanged parent compound.^6,7

        • Excretion

          • Elimination is almost exclusively via the kidneys.

            • Over 97% of an administered dose is recovered unchanged in the urine.

            • The elimination half-life is approximately 2.7 hours. ^1,6  

      • Therapeutic Uses: ceftazidime-avibactam is appropriate for difficult Gram-negative infections. FDA-approved indications include:^10,11

        • Complicated urinary tract infections (cUTIs), including pyelonephritis, due to susceptible Gram-negative bacteria (including many ESBL and some carbapenemase producers).

        • Complicated intra-abdominal infections (cIAIs) (used in combination with metronidazole for anaerobic coverage),

          • This combination is typically effective against resistant Enterobacteriaceae in intra-abdominal abscesses or infections.

        • Hospital-acquired and ventilator-associated pneumonia (HABP/VABP) due to Gram-negative rods, including P. aeruginosa and Enterobacterales that are not susceptible to other agents.¹¹

August, 2025