Understanding Aztreonam: A Unique Monobactam Antibiotic
Aztreonam represents a unique class of beta-lactam antibiotics known as monobactams [1.2.3]. Unlike other beta-lactams such as penicillins and cephalosporins, which have a fused ring structure, aztreonam possesses a standalone, monocyclic beta-lactam ring [1.2.1, 1.2.2]. This structural distinction is fundamental to its mechanism of action and its safety profile, particularly in patients with allergies to other beta-lactam antibiotics [1.3.3]. It is sold under brand names including Azactam® for injection and Cayston® for inhalation [1.2.2, 1.4.3].
Mechanism of Action
Like other beta-lactam antibiotics, aztreonam works by inhibiting the synthesis of the bacterial cell wall, which is crucial for the bacterium's survival [1.3.3]. It specifically targets and binds with high affinity to penicillin-binding protein 3 (PBP-3) [1.2.1]. This binding action disrupts the final step of peptidoglycan synthesis in the bacterial cell wall, leading to the formation of long, unstable bacterial filaments and ultimately causing cell lysis and death [1.2.1]. Its high selectivity for PBP-3 of Gram-negative aerobic bacteria is a key reason for its targeted spectrum of activity [1.2.1].
Spectrum of Activity: A Specialized Focus
Aztreonam's clinical utility is defined by its narrow and specific spectrum of activity. It is highly effective against a wide range of aerobic Gram-negative bacteria but has no clinically useful activity against Gram-positive bacteria or anaerobic bacteria [1.2.3, 1.3.2, 1.14.3].
Effective against:
- Enterobacteriaceae: Including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Serratia marcescens [1.3.3, 1.4.2].
- Pseudomonas aeruginosa: Aztreonam is active against this often multi-drug resistant pathogen, making it a vital option for certain infections [1.2.3].
- Haemophilus influenzae [1.3.3].
- Neisseria gonorrhoeae [1.3.3].
Not effective against:
- Gram-positive bacteria: Such as Staphylococcus and Streptococcus species [1.3.2].
- Anaerobic bacteria: Including Bacteroides fragilis [1.3.2].
- Atypical bacteria: Such as Legionella [1.2.2].
This targeted spectrum means that when used alone, aztreonam has a minimal effect on the normal anaerobic flora of the gut [1.2.3].
Clinical Applications and Administration
Aztreonam is FDA-approved for treating a variety of infections caused by susceptible Gram-negative organisms [1.2.2, 1.4.2]. Due to its poor oral absorption (less than 1%), it must be administered parenterally, either intravenously (IV) or intramuscularly (IM), for systemic infections [1.2.3, 1.4.1]. An inhaled formulation, aztreonam lysine (Cayston), is specifically used to manage chronic Pseudomonas aeruginosa lung infections in patients with cystic fibrosis [1.3.1, 1.12.1, 1.12.2].
Common indications for injectable aztreonam (Azactam) include:
- Urinary Tract Infections (UTIs): Both complicated and uncomplicated [1.4.2, 1.13.1].
- Lower Respiratory Tract Infections: Such as pneumonia and bronchitis [1.4.2].
- Septicemia (bloodstream infections) [1.4.2].
- Skin and Skin-Structure Infections [1.4.2].
- Intra-abdominal Infections: Often used in combination with an agent covering anaerobes, like metronidazole [1.2.2].
- Gynecologic Infections [1.4.2].
A crucial role for aztreonam is in treating Gram-negative infections in patients with a history of severe, IgE-mediated penicillin allergy [1.2.2, 1.6.1]. Its unique monobactam structure results in a lack of cross-reactivity with most other beta-lactams, making it a safer alternative in this population [1.3.3]. The only notable exception is a potential cross-reactivity with ceftazidime, due to an identical side chain [1.2.2].
Aztreonam Compared to Other Antibiotics
To understand aztreonam's place in therapy, it is useful to compare it with other antibiotics used for similar indications.
| Feature | Aztreonam | Meropenem (A Carbapenem) | Tobramycin (An Aminoglycoside) |
|---|---|---|---|
| Class | Monobactam [1.2.2] | Carbapenem | Aminoglycoside [1.8.1] |
| Mechanism | Inhibits cell wall synthesis (PBP-3) [1.2.1] | Inhibits cell wall synthesis (multiple PBPs) | Inhibits protein synthesis |
| Gram-Negative | Good (including Pseudomonas) [1.2.3] | Excellent (including Pseudomonas) | Excellent (including Pseudomonas) [1.8.1] |
| Gram-Positive | None [1.3.2] | Good | None |
| Anaerobes | None [1.3.2] | Excellent | None |
| Penicillin Allergy | Generally safe (low cross-reactivity) [1.6.1] | Contraindicated in severe allergy | Safe to use |
| Primary Use | Gram-negative infections, esp. in penicillin allergy [1.3.3] | Broad-spectrum, severe/mixed infections | Gram-negative infections, synergy, CF (inhaled) [1.8.1] |
| Formulations | IV, IM, Inhaled [1.11.2, 1.11.1] | IV | IV, IM, Inhaled, Ophthalmic [1.8.1] |
Resistance, Side Effects, and Conclusion
Bacterial resistance to aztreonam can occur, primarily through the production of certain beta-lactamase enzymes (like ESBLs and AmpC) that can hydrolyze the drug, or through mutations in penicillin-binding protein 3 [1.3.1, 1.9.1, 1.9.2]. To combat some forms of resistance, aztreonam is sometimes combined with a beta-lactamase inhibitor like avibactam [1.9.1].
Aztreonam is generally well-tolerated. The most common side effects include local reactions at the injection site (pain, swelling), diarrhea, nausea, and rash [1.4.1, 1.5.1]. Serious side effects are rare but can include severe diarrhea (Clostridioides difficile-associated) and allergic reactions [1.5.1, 1.5.3].
In conclusion, aztreonam is a valuable monobactam antibiotic with a specialized but critical role in medicine. Its focused activity against aerobic Gram-negative pathogens, including P. aeruginosa, and its favorable safety profile in most penicillin-allergic patients secure its position as an important therapeutic agent for specific and challenging infections [1.2.2, 1.3.3].
For more information from an authoritative source, you can visit the Aztreonam page on MedlinePlus. [1.4.1]
