Aztreonam

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 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 Y
ATC code	J01DF01
PubChem	CID 54116
DrugBank	APRD00815
ChemSpider	4674940 Y
UNII	G2B4VE5GH8 Y
KEGG	D00240 Y
ChEBI	CHEBI:161680 Y
ChEMBL	CHEMBL158 Y
Chemical data
Formula	C13H17N5O8S2
Mol. mass	435.433 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C13H17N5O8S2/c1-5-7(10(20)18(5)28(23,24)25)16-9(19)8(6-4-27-12(14)15-6)17-26-13(2,3)11(21)22/h4-5,7H,1-3H3,(H2,14,15)(H,16,19)(H,21,22)(H,23,24,25)/b17-8-/t5-,7-/m0/s1 Y Key:WZPBZJONDBGPKJ-VEHQQRBSSA-N Y
N(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

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 (PBP-3) and mild affinity for PBP-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.

Indications and spectrum of activity

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.^[2]

Synergism between aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa has been suggested.^[3]

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

Administration

Aztreonam is poorly absorbed when given via the oral route, 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 inhalative form on February 22, 2010 for the suppression of Pseudomonas aeruginosa infections in patients with cystic fibrosis.^[4] It received conditional approval for administration in Canada and the European Union September 2009,^[4] and has been fully approved in Australia.^[5]

Common adverse 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 un-fused beta-lactam ring unique to aztreonam, there is limited cross-reactivity between aztreonam and other beta-lactam antibiotics, and it is generally considered safe to admininister aztreonam to patients with hypersensitivity (allergies) to penicillins.^[1]

Aztreonam is considered Pregnancy category B.

References

1. ^ ^{a b} AHFS DRUG INFORMATION 2006 (2006 ed.). American Society of Health-System Pharmacists. 2006. 
2. ^ Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc.. 2006. 
3. ^ 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. 
4. ^ ^{a b} Larkin, Catherine (February 22, 2010). "Gilead’s Inhaled Antibiotic for Lungs Wins Approval". BusinessWeek. http://www.businessweek.com/news/2010-02-22/gilead-s-inhaled-antibiotic-for-lungs-wins-approval-update1-.html. Retrieved 2010-03-05. 
5. ^ "FDA approves Gilead cystic fibrosis drug Cayston". BusinessWeek. February 23, 2010. http://www.businessweek.com/ap/financialnews/D9E237QG1.htm. Retrieved 2010-03-05. 

External links

• MedlinePlus DrugInfo uspdi-202078