Avibactam sodium
[CAS# 1192491-61-4]

Identification

• Classification: API >> Antibiotics
• Name: Avibactam sodium
• Synonyms: (2S,5R)-7-Oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide monosodium salt; NXL 104
• Molecular Formula: C₇H₁₀N₃O₆S.Na
• Molecular Weight: 287.23
• CAS Registry Number: 1192491-61-4
• EC Number: 834-591-9
• SMILES: C1C[C@H](N2C[C@@H]1N(C2=O)OS(=O)(=O)[O-])C(=O)N.[Na+]

Properties

• Solubility: 10 mM (water), 69 mg/ml (DMSO)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

Avibactam sodium is a novel non-β-lactam β-lactamase inhibitor with a molecular formula of C₇H₁₀N₃NaO₆S and a molecular weight of 293.22 g/mol. It is known for its ability to restore the efficacy of β-lactam antibiotics and is important in the fight against antibiotic-resistant bacterial infections.

Avibactam was discovered during research efforts to address the growing threat of antibiotic resistance. Traditional β-lactamase inhibitors, such as clavulanic acid, have limitations against certain resistant strains. Scientists at Novexel (later acquired by AstraZeneca and subsequently by Pfizer) developed avibactam to target a wider range of β-lactamases, including class A, C, and some class D enzymes. The discovery of the drug was reported in the late 2000s, and by 2015, avibactam sodium received FDA approval in combination with ceftazidime for the treatment of complicated intra-abdominal and urinary tract infections.

Avibactam inhibits β-lactamases, enzymes produced by bacteria that hydrolyze β-lactam antibiotics, rendering them ineffective. Unlike conventional inhibitors, avibactam is a diazabicyclooctane (DBO) that covalently but reversibly binds to β-lactamases, thereby preserving the antibiotic's structure and allowing it to inhibit bacterial cell wall synthesis.

Avibactam is not used alone, but in combination with ceftazidime, an established β-lactam antibiotic. The combination (marketed as Avycaz in the United States and Zavicefta in Europe) is effective in treating infections caused by resistant Gram-negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa.

It is particularly effective against complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI), including cases where other treatments have failed. Avibactam's ability to fight beta-lactamase-producing bacteria makes it a key option in these situations.

Ongoing studies are exploring combining avibactam with other beta-lactam antibiotics, with the goal of expanding its use against a wider range of pathogens and developing new treatment options for multidrug-resistant infections.

References

2009. In vitro activity of the {beta}-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases. The Journal of antimicrobial chemotherapy.
DOI: 10.1093/jac/dkp197

2010. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor. Antimicrobial Agents and Chemotherapy.
DOI: 10.1128/aac.00568-10

2024. The Challenge of Treating Infections Caused by Metallo‐&bets;‐Lactamase-Producing Gram-Negative Bacteria: A Narrative Review. Drugs.
DOI: 10.1007/s40265-024-02102-8