Avibactam

Chemical Identity

Property	Value
Chemical Formula	C7H11N3O6S
Molecular Weight	265.24 Da
CAS Number	1192500-31-4
Peptide Class	Diazabicyclooctane (DBO)
Type	Non-beta-lactam beta-lactamase inhibitor

Structure

Avibactam is a novel non-beta-lactam beta-lactamase inhibitor based on a diazabicyclooctane (DBO) core. Unlike classical inhibitors (clavulanate, tazobactam, sulbactam), avibactam does not contain a beta-lactam ring. It features a sulfonate group that participates in a reversible covalent mechanism with serine beta-lactamases.

Mechanism of Action

Avibactam forms a reversible covalent bond with the active site serine of class A, class C, and some class D beta-lactamases, including KPC carbapenemases. Unlike irreversible inhibitors, avibactam is slowly released from the enzyme (deacylation), regenerating both the inhibitor and the enzyme. This reversible mechanism provides sustained inhibition.

Clinical Applications

• Complicated intra-abdominal infections: Ceftazidime-avibactam (Avycaz)
• Complicated UTIs: Including pyelonephritis
• Hospital-acquired pneumonia: Including VAP
• CRE infections: KPC-producing Enterobacterales

Pharmacokinetics

• Half-life: 2 hours (with ceftazidime)
• Protein binding: 5.7-8.2%
• Elimination: Renal (97% unchanged)
• Dosing: 0.5 g with ceftazidime 2 g every 8 hours
• Route: IV infusion

Safety and Side Effects

Nausea, diarrhea, vomiting, headache, and Clostridioides difficile infection. Generally well-tolerated. No significant drug interactions beyond the partner beta-lactam.

References

• Ehmann, D.E., et al. (2012). Avibactam covalently inhibits beta-lactamases. Proceedings of the National Academy of Sciences, 109, 11663-11668.
• Lucasti, C., et al. (2014). Ceftazidime-avibactam for intra-abdominal infections. Journal of Antimicrobial Chemotherapy, 69, 2156-2167.