Aztreonam
[CAS# 149496-40-2]

Identification

• Classification: API >> Antibiotics >> Beta-lactamase inhibitor
• Name: Aztreonam
• Synonyms: 2-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid
• Molecular Formula: C₁₃H₁₇N₅O₈S₂
• Molecular Weight: 435.43
• CAS Registry Number: 149496-40-2
• 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

• 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

Discovory and Applicatios

Aztreonam is a synthetic monobactam antibiotic first discovered in the late 1970s as part of efforts to develop novel β-lactam antibiotics with enhanced activity against Gram-negative bacteria. It is unique among β-lactam antibiotics due to its monocyclic β-lactam ring structure, distinguishing it from penicillins and cephalosporins, which possess bicyclic structures. This distinct chemical structure contributes to its specific spectrum of antibacterial activity and resistance profile.

Aztreonam’s discovery was motivated by the increasing need for antibiotics effective against Gram-negative aerobic bacteria, especially those resistant to existing treatments. Its molecular design targets the bacterial cell wall synthesis by binding to penicillin-binding protein 3 (PBP3), which plays a critical role in bacterial cell division. By inhibiting PBP3, Aztreonam disrupts cell wall synthesis, leading to bacterial cell death.

The antibiotic is primarily effective against aerobic Gram-negative bacteria, including pathogens such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, and Haemophilus influenzae. Notably, Aztreonam shows no significant activity against Gram-positive bacteria or anaerobes, which is important for its clinical use. It is also resistant to many β-lactamases produced by Gram-negative bacteria, including some extended-spectrum β-lactamases (ESBLs), which contribute to its effectiveness in treating infections caused by resistant strains.

Aztreonam is administered mainly by intravenous or intramuscular injection, allowing it to reach systemic infections effectively. It has been used in the treatment of various infections such as urinary tract infections, lower respiratory tract infections, septicemia, intra-abdominal infections, and skin and soft tissue infections caused by susceptible Gram-negative bacteria. It is particularly valuable for patients who are allergic to penicillins and cephalosporins because it generally does not exhibit cross-reactivity with these classes.

Clinically, Aztreonam’s safety and tolerability profile have been well established, and it is often reserved for specific infections where its narrow but potent activity spectrum is advantageous. Its resistance to many β-lactamases enhances its utility in healthcare settings with high prevalence of resistant Gram-negative bacteria.

In addition to its therapeutic applications, Aztreonam’s development contributed to the broader understanding of β-lactam antibiotic mechanisms and resistance. It paved the way for designing other monobactam antibiotics and informed strategies to overcome bacterial resistance through molecular modification.

In summary, Aztreonam is a monobactam antibiotic discovered to target Gram-negative aerobic bacteria with specificity and resistance to certain β-lactamases. Its clinical applications focus on treating infections caused by susceptible Gram-negative pathogens, especially in patients with allergies to other β-lactams, making it an important option in antimicrobial therapy.

References

1986. Beta-Lactamase Stability and in vitro Activity of Aztreonam, with a Comparison to 9 Other Beta-Lactam Antibiotics and Gentamicin. Chemotherapy, 32(4).
DOI: 10.1159/000238431

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).
DOI: 10.1016/0091-6749(91)90215-A

2003. In vitro Synergy Studies Using Aztreonam and Fluoroquinolone Combinations against Six Species of Gram-Negative Bacilli. Chemotherapy, 49(1-2).
DOI: 10.1159/000069786