Aztreonam
[CAS# 78110-38-0]

Identification

• Classification: API >> Antibiotics >> Beta-lactamase inhibitor
• Name: Aztreonam
• Synonyms: [2S-[2a,3b(Z)]]-2-[[[1-(2-Amino-4-thiazolyl)-2-[(2-methyl-4-oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid
• Molecular Formula: C₁₃H₁₇N₅O₈S₂
• Molecular Weight: 435.43
• CAS Registry Number: 78110-38-0
• EC Number: 278-839-9
• SMILES: C[C@H]1[C@@H](C(=O)N1S(=O)(=O)O)NC(=O)/C(=N\OC(C)(C)C(=O)O)/C2=CSC(=N2)N

Properties

• Density: 1.83 g/mL
• Solubility: DMSO 87 mg/mL, Water 11 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Danger
• Hazard Statements: H315-H317-H334-H372-H400
• Precautionary Statements: P233-P260-P261-P264-P270-P271-P272-P273-P280-P284-P302+P352-P304+P340-P319-P321-P332+P317-P333+P317-P342+P316-P362+P364-P391-P403-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Respiratory sensitization	Resp. Sens.	1	H334
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin sensitization	Skin Sens.	1	H317

Discovory and Applicatios

Aztreonam is a synthetic monobactam antibiotic belonging to the beta-lactam class, characterized by its unique monocyclic beta-lactam ring structure. It was discovered in the 1980s during research efforts to develop new antibiotics effective against Gram-negative bacterial infections, particularly those resistant to other beta-lactam antibiotics.

The mechanism of action of aztreonam involves the inhibition of bacterial cell wall synthesis. It binds selectively to penicillin-binding protein 3 (PBP-3), an enzyme essential for the cross-linking of peptidoglycan strands in the bacterial cell wall. This binding disrupts the construction of the cell wall, leading to cell lysis and death of susceptible bacteria.

Aztreonam exhibits potent activity primarily against aerobic Gram-negative bacteria, including species such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Haemophilus influenzae. However, it lacks significant activity against Gram-positive bacteria and anaerobes. This selective spectrum is clinically useful in treating infections caused by multidrug-resistant Gram-negative pathogens.

Clinically, aztreonam is used to treat a variety of infections, including urinary tract infections, lower respiratory tract infections, intra-abdominal infections, septicemia, and skin and soft tissue infections caused by susceptible Gram-negative organisms. It is often employed in patients allergic to penicillins or cephalosporins due to its low cross-reactivity with other beta-lactams.

Aztreonam can be administered intravenously, intramuscularly, or via inhalation for respiratory infections, particularly in patients with cystic fibrosis to target Pseudomonas aeruginosa colonization. Its pharmacokinetic profile allows for effective concentrations in the blood and tissues, contributing to its clinical efficacy.

The safety profile of aztreonam is generally favorable, with common adverse effects including local reactions at the injection site, gastrointestinal disturbances, and occasional allergic reactions. Because of its narrow spectrum, aztreonam is less likely to disrupt normal flora compared to broad-spectrum antibiotics.

Resistance to aztreonam can occur, primarily through the production of beta-lactamases such as extended-spectrum beta-lactamases (ESBLs) or metallo-beta-lactamases by bacteria, which can hydrolyze the beta-lactam ring and inactivate the drug.

In summary, aztreonam is a monobactam antibiotic selectively active against aerobic Gram-negative bacteria. Since its discovery, it has become a valuable therapeutic option for treating resistant infections, particularly in patients with beta-lactam allergies, contributing to the management of challenging bacterial infections in clinical practice.

References

1987. In vitro activities of aztreonam, imipenem, and amoxycillin-clavulanate against ampicillin-resistant Haemophilus influenzae. Antimicrobial Agents and Chemotherapy, 31(12).
DOI: 10.1128/aac.31.12.1871

1991. Sensitization to aztreonam and cross-reactivity with other beta-lactam antibiotics in high-risk patients with cystic fibrosis. The Journal of Allergy and Clinical Immunology, 87(1 Pt 1).
DOI: 10.1016/0091-6749(91)90215-a

2007. Enterobacteriaceae Bloodstream Infections: Presence of Integrons, Risk Factors, and Outcome. Antimicrobial Agents and Chemotherapy, 51(7).
DOI: 10.1128/aac.00044-07