Aztreonam

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Aztreonam
Aztreonam structure.svg
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 cat. B1 (Au), B (U.S.)
Legal status ℞-only (U.S.)
Routes Intravenous, intramuscular, inhalation
Pharmacokinetic data
Bioavailability 100% (IM)
Protein binding 56%
Metabolism hepatic (minor %)
Half-life 1.7 hours
Excretion Renal
Identifiers
CAS number 78110-38-0 YesY
ATC code J01DF01
PubChem CID 54116
DrugBank DB00355
ChemSpider 4674940 YesY
UNII G2B4VE5GH8 YesY
KEGG D00240 YesY
ChEBI CHEBI:161680 YesY
ChEMBL CHEMBL158 YesY
Chemical data
Formula C13H17N5O8S2 
Mol. mass 435.433 g/mol
 YesY (what is this?)  (verify)

Aztreonam (trade names Azactam injection, Cayston inhalation) is a synthetic monocyclic beta-lactam antibiotic (a monobactam), with the nucleus based on a simpler monobactam isolated from Chromobacterium violaceum. It was approved by the U.S. Food and Drug Administration (FDA) in 1986. It is resistant to some beta-lactamases, but is inactivated by extended-spectrum beta-lactamases.

Mechanism of action[edit]

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.[1] Aztreonam is bactericidal, but less so than some of the cephalosporins.

Spectrum of bacterial susceptibility and resistance[edit]

Acinetobacter anitratus, Escherichia coli, and Proteus mirabilis are generally susceptible to aztreonam, while some Pseudomonas aeruginosa, 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.[2]

Indications and spectrum of activity[edit]

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.[3] 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

[4]

Synergism between aztreonam and arbekacin or tobramycin against P. aeruginosa has been suggested.[5]

Aztreonam is often used in patients who are penicillin allergic or who cannot tolerate aminoglycosides.

Administration[edit]

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.[6] It received conditional approval for administration in Canada and the European Union in September 2009,[6] and has been fully approved in Australia.[7]

Common adverse effects[edit]

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, limited cross-reactivity between aztreonam and other beta-lactam antibiotics occurs, and it is generally considered safe to admininister aztreonam to patients with hypersensitivity (allergies) to penicillins.[1]

Aztreonam is considered pregnancy category B.

References[edit]

  1. ^ a b AHFS DRUG INFORMATION 2006 (2006 ed.). American Society of Health-System Pharmacists. 2006. 
  2. ^ "Aztreonam spectrum of bacterial susceptibility and Resistance". Retrieved 15 May 2012. 
  3. ^ Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc. 2006. 
  4. ^ http://www.toku-e.com/Assets/MIC/Aztreonam.pdf
  5. ^ 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. 
  6. ^ a b Larkin, Catherine (February 22, 2010). "Gilead’s Inhaled Antibiotic for Lungs Wins Approval". BusinessWeek. Retrieved 2010-03-05. 
  7. ^ "FDA approves Gilead cystic fibrosis drug Cayston". BusinessWeek. February 23, 2010. Retrieved 2010-03-05. 

External links[edit]