Aztreonam
 | |
| Systematic (IUPAC) name | |
|---|---|
|
2-{[(1Z)-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 | |
| Clinical data | |
| Trade names | Azactam |
| AHFS/Drugs.com | monograph |
| Pregnancy category | |
| Routes of administration | Intravenous, intramuscular, inhalation |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 100% (IM) 0.1% (Oral in Rats) Unknown (Oral in humans) |
| Protein binding | 56% |
| Metabolism | hepatic (minor %) |
| Biological half-life | 1.7 hours |
| Excretion | Renal |
| Identifiers | |
| CAS Number |
78110-38-0  |
| ATC code | J01DF01 (WHO) |
| PubChem | CID 54116 |
| DrugBank |
DB00355 |
| ChemSpider |
4674940 |
| UNII |
G2B4VE5GH8 |
| KEGG |
D00240 |
| ChEBI |
CHEBI:161680 |
| ChEMBL |
CHEMBL158 |
| Chemical data | |
| Formula | C13H17N5O8S2 |
| Molar mass | 435.433 g/mol |
| |
| |
| (verify) | |
Aztreonam (trade names Azactam injection, Cayston inhalation) is a monobactam antibiotic used primarily to treat infections caused by gram-negative bacteria. It is a synthetic drug based on a simpler monobactam isolated from Chromobacterium violaceum. It is resistant to some beta-lactamases, but is inactivated by extended-spectrum beta-lactamases.
It was approved by the U.S. Food and Drug Administration (FDA) in 1986.
Medical uses
Aztreonam has strong activity against susceptible Gram-negative bacteria, including Pseudomonas aeruginosa. It has no useful activity against Gram-positive bacteria or anaerobes. It is known to be effective against a wide range of bacteria including Citrobacter, Enterobacter, E. coli, Haemophilus, Klebsiella, Proteus, and Serratia species.[1] The following represents MIC susceptibility data for a few medically significant microorganisms.
- Staphylococcus aureus 8 - >128 μg/ml
- Staphylococcus epidermidis 8 - 32 μg/ml
- Streptococcus pyogenes 8 - ≥128 μg/ml
Synergism between aztreonam and arbekacin or tobramycin against P. aeruginosa has been suggested.[3]
Spectrum of bacterial susceptibility and resistance
Acinetobacter anitratus, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis are generally susceptible to aztreonam, while some staphylococci, Staphylococcus aureus, Staphylococcus hemolyticus and Xanthomonas maltophilia are resistant to it. Furthermore, Aeromonas hydrophila, Citrobacter diversus, Enterobacter agglomerans, Haemophilus spp. and Streptococcus pyogenes have developed resistance to aztreonam to varying degrees.[4]
Aztreonam is often used in patients who are penicillin allergic or who cannot tolerate aminoglycosides.
Administration
Aztreonam is poorly absorbed when given orally, so it must be administered as an intravenous or intramuscular injection (trade name Azactam ), or inhaled (trade name Cayston) using an ultrasonic nebulizer. In the United States, the FDA approved the inhalation form on February 22, 2010, for the suppression of P. aeruginosa infections in patients with cystic fibrosis.[5] It received conditional approval for administration in Canada and the European Union in September 2009,[5] and has been fully approved in Australia.[6]
Side effects
Reported side effects include injection site reactions, rash, and rarely toxic epidermal necrolysis. Gastrointestinal side effects generally include diarrhea and nausea and vomiting. There may be drug-induced eosinophilia. Because of the unfused beta-lactam ring unique to aztreonam, there is somewhat lower cross-reactivity between aztreonam and many other beta-lactam antibiotics, and it may be safe to administer aztreonam to many patients with hypersensitivity (allergies) to penicillins and nearly all cephalosporins. [7] However, like other beta lactams, there is a risk of very serious allergic reactions, including anaphylaxis. The aztreonam label directs physicians to be aware of the possibility of these severe adverse reactions. This is more likely if the patient is allergic to a certain cephalosporin known as ceftazidime. Azetreonam exhibits cross-reactivity with this cephalosporin due to a similar side chain. Physicians should evaluate prior allergy history when prescribing this medicine.
Special caution is warranted in patients who are allergic to ceftazidime and are subsequently placed on aztreonam therapy.
Mechanism of action
Aztreonam is similar in action to penicillin. It inhibits mucopeptide synthesis in the bacterial cell wall, thereby blocking peptidoglycan crosslinking. It has a very high affinity for penicillin-binding protein-3 and mild affinity for penicillin-binding protein-1a. Aztreonam binds the penicillin-binding proteins of Gram-positive and anaerobic bacteria very poorly and is largely ineffective against them.[7] Aztreonam is bactericidal, but less so than some of the cephalosporins.
References
- ↑ Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc. 2006.
- ↑ http://www.toku-e.com/Assets/MIC/Aztreonam.pdf
- ↑ Kobayashi, Y., Uchida, H., Kawakami Y. (1992). "Synergy with aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa isolated from blood". J Antimicrob Chemother 30 (6): 871–872. doi:10.1093/jac/30.6.871. PMID 1289363.
- ↑ "Aztreonam spectrum of bacterial susceptibility and Resistance" (PDF). Retrieved 15 May 2012.
- 1 2 Larkin, Catherine (February 22, 2010). "Gilead’s Inhaled Antibiotic for Lungs Wins Approval". BusinessWeek. Retrieved 2010-03-05.
- ↑ "FDA approves Gilead cystic fibrosis drug Cayston". BusinessWeek. February 23, 2010. Retrieved 2010-03-05.
- 1 2 AHFS DRUG INFORMATION 2006 (2006 ed.). American Society of Health-System Pharmacists. 2006.
External links
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||