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Identification
NameAztreonam
Accession NumberDB00355  (APRD00815, EXPT00605)
TypeSmall Molecule
GroupsApproved
Description

A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with gram-positive organisms. [PubChem]

Structure
Thumb
Synonyms
(Z,)-2-((((2-Amino-4-thiazolyl)(((2S,3S,)-2-methyl-4-oxo-1-sulfo-3-azetidinyl)carbamoyl)methylene)amino)oxy)-2-methylpropionic acid
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
Azactam
Aztreonam
Aztréonam
Aztreonamum
Primbactam
External Identifiers
  • Corus 1020
  • SQ 26776
  • UNII-XNM7LT65NP
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Azactaminjection, solution1 g/50mLintravenousE.R. Squibb & Sons, L.L.C.2010-04-01Not applicableUs
Azactaminjection, powder, for solution1 g/1intramuscular; intravenousCardinal Health2009-06-01Not applicableUs
Azactaminjection, powder, for solution2 g/1intramuscular; intravenousE.R. Squibb & Sons, L.L.C.2010-04-01Not applicableUs
Azactaminjection, powder, for solution1 g/1intramuscular; intravenousE.R. Squibb & Sons, L.L.C.2010-04-01Not applicableUs
Azactaminjection, solution2 g/50mLintravenousE.R. Squibb & Sons, L.L.C.2010-04-01Not applicableUs
Caystonpowder for solution75 mginhalationGilead Sciences Canada Inc2009-11-11Not applicableCanada
CaystonkitGilead Sciences, Inc.2010-02-22Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aztreonaminjection, powder, lyophilized, for solution1 g/1intramuscular; intravenousFresenius Kabi USA, LLC2009-11-05Not applicableUs
Aztreonaminjection, powder, lyophilized, for solution2 g/1intramuscular; intravenousFresenius Kabi USA, LLC2009-11-05Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AzenamAristo
AztramShanxi C & Y
AztreoZydus Cadila
BencipenAC Farma
PrimbactamMenarini
TrezamGlenmark
VebacFahrenheit
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Aztreonam Lysine
ThumbNot applicableDBSALT001061
Categories
UNIIG2B4VE5GH8
CAS number78110-38-0
WeightAverage: 435.433
Monoisotopic: 435.051853925
Chemical FormulaC13H17N5O8S2
InChI KeyInChIKey=WZPBZJONDBGPKJ-VEHQQRBSSA-N
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
IUPAC Name
(2S,3S)-3-[(2Z)-2-(2-azaniumyl-1,3-thiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetamido]-2-methyl-4-oxoazetidine-1-sulfonate
SMILES
C[[email protected]]1[[email protected]](NC(=O)C(=N/OC(C)(C)C(=O)O)\C2=CSC([NH3+])=N2)C(=O)N1S([O-])(=O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as monobactams. These are compounds comprising beta-lactam ring is alone and not fused to another ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentMonobactams
Alternative Parents
Substituents
  • Monobactam
  • N-acyl-alpha amino acid or derivatives
  • 2,4-disubstituted 1,3-thiazole
  • Heteroaromatic compound
  • Thiazole
  • Organic sulfuric acid or derivatives
  • Azole
  • Secondary carboxylic acid amide
  • Oxime ether
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of the following infections caused by susceptible gram-negative microorganisms: urinary tract infections, lower respiratory tract infections, septicemia, skin and skin-structure infections, intra-abdominal infections, and gynecologic infections.
PharmacodynamicsAztreonam is a monocyclic beta-lactam antibiotic (a monobactam) originally isolated from Chromobacterium violaceum. Aztreonam exhibits potent and specific activity in vitro against a wide spectrum of gram-negative aerobic pathogens including Pseudomonas aeruginosa. It has no useful activity against gram-positive bacteria or anaerobes, but has very broad spectrum against gram-negative aerobes, including Pseudomonas aeruginosa. This has given it the nickname "the magic bullet for aerobic gram-negative bacteria". Aztreonam, unlike the majority of beta-lactam antibiotics, does not induce beta-lactamase activity and its molecular structure confers a high degree of resistance to hydrolysis by beta-lactamases (such as penicillinases and cephalosporinases) produced by most gram-negative and gram-positive pathogens; it is, therefore, usually active against gram-negative aerobic microorganisms that are resistant to antibiotics hydrolyzed by beta-lactamases. It is active against many strains that are multiply-resistant to other antibiotics, such as certain cephalosporins, penicillin, and aminoglycosides. Aztreonam maintains its antimicrobial activity over a pH range of 6 to 8 in vitro, as well as in the presence of human serum and under anaerobic conditions.
Mechanism of actionThe bactericidal action of aztreonam results from the inhibition of bacterial cell wall synthesis due to a high affinity of aztreonam for penicillin binding protein 3 (PBP3). By binding to PBP3, aztreonam inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that aztreonam interferes with an autolysin inhibitor.
Related Articles
AbsorptionLess than 1% absorbed from the gastrointestinal tract following oral administration. Completely absorbed following intramuscular administration.
Volume of distribution
  • 12.6 L
Protein bindingSerum protein binding averaged 56% and is independent of dose. Impaired renal function, 36 to 43%.
Metabolism

Approximately 6 to 16% metabolized to inactive metabolites by hydrolysis of the beta-lactam bond, resulting in an open-ring compound.

Route of eliminationIn healthy subjects, aztreonam is excreted in the urine about equally by active tubular secretion and glomerular filtration. Urinary excretion of a single parenteral dose was essentially complete by 12 hours after injection.
Half lifeThe serum half-life of aztreonam averaged 1.7 hours (1.5 to 2.0) in subjects with normal renal function, independent of the dose. In elderly patients and in patients with impaired renal function, the mean serum half-life of aztreonam increased (4.7 to 6 hours and 2.1 hours, respectively).
Clearance
  • 91 mL/min [healthy]
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9601
Blood Brain Barrier-0.9657
Caco-2 permeable-0.5885
P-glycoprotein substrateNon-substrate0.6472
P-glycoprotein inhibitor INon-inhibitor0.8047
P-glycoprotein inhibitor IINon-inhibitor0.6293
Renal organic cation transporterNon-inhibitor0.9324
CYP450 2C9 substrateNon-substrate0.7736
CYP450 2D6 substrateNon-substrate0.8142
CYP450 3A4 substrateNon-substrate0.5784
CYP450 1A2 substrateNon-inhibitor0.8562
CYP450 2C9 inhibitorNon-inhibitor0.8404
CYP450 2D6 inhibitorNon-inhibitor0.9023
CYP450 2C19 inhibitorNon-inhibitor0.8306
CYP450 3A4 inhibitorNon-inhibitor0.8763
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9005
Ames testNon AMES toxic0.6319
CarcinogenicityCarcinogens 0.5839
BiodegradationNot ready biodegradable0.8146
Rat acute toxicity1.9822 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9967
hERG inhibition (predictor II)Non-inhibitor0.8329
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Gilead sciences inc
  • Bristol myers squibb
  • Bristol myers squibb co
  • App pharmaceuticals llc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, for solutionintramuscular; intravenous1 g/1
Injection, powder, for solutionintramuscular; intravenous2 g/1
Injection, solutionintravenous1 g/50mL
Injection, solutionintravenous2 g/50mL
Injection, powder, lyophilized, for solutionintramuscular; intravenous1 g/1
Injection, powder, lyophilized, for solutionintramuscular; intravenous2 g/1
Kit
Powder for solutioninhalation75 mg
Prices
Unit descriptionCostUnit
Azactam 2 gm vial81.4USD vial
Cayston 75 mg inhal solution63.24USD ml
Azactam 1 gm vial40.78USD vial
Azactam-iso-osmot 2 gm/50 ml1.6USD ml
Azactam-iso-osmot 1 gm/50 ml0.8USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1338670 No1996-10-222013-10-22Canada
CA1340253 No1998-12-152015-12-15Canada
US7208141 No2001-12-202021-12-20Us
US7214364 No2001-12-202021-12-20Us
US7427633 No2001-12-202021-12-20Us
US8399496 No2001-12-202021-12-20Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0429 mg/mLALOGPS
logP0.04ALOGPS
logP-3.1ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)-1.9ChemAxon
pKa (Strongest Basic)4.14ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area206.03 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity102.09 m3·mol-1ChemAxon
Polarizability39.94 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Neal G. Anderson, Carl F. Anderson, “Delta form of aztreonam and preparation thereof.” U.S. Patent US4826973, issued January, 1983.

US4826973
General ReferencesNot Available
External Links
ATC CodesJ01DF01
AHFS CodesNot Available
PDB Entries
FDA labelDownload (1.57 MB)
MSDSDownload (42 KB)
Interactions
Drug Interactions
Drug
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Aztreonam.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Bacillus subtilis (strain 168)
Pharmacological action
yes
Actions
inhibitor
General Function:
Penicillin binding
Specific Function:
Not Available
Gene Name:
pbpC
Uniprot ID:
P42971
Molecular Weight:
74405.915 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Rittenbury MS: How and why aztreonam works. Surg Gynecol Obstet. 1990;171 Suppl:19-23. [PubMed:2244291 ]
  4. Mock CN, Jurkovich GJ, Dries DJ, Maier RV: Clinical significance of antibiotic endotoxin-releasing properties in trauma patients. Arch Surg. 1995 Nov;130(11):1234-40; discussion 1240-1. [PubMed:7487468 ]
  5. Fung-Tomc J, Bush K, Minassian B, Kolek B, Flamm R, Gradelski E, Bonner D: Antibacterial activity of BMS-180680, a new catechol-containing monobactam. Antimicrob Agents Chemother. 1997 May;41(5):1010-6. [PubMed:9145861 ]
Kind
Protein
Organism
Citrobacter freundii
Pharmacological action
yes
Actions
potentiator
General Function:
Beta-lactamase activity
Specific Function:
This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
Gene Name:
ampC
Uniprot ID:
P05193
Molecular Weight:
41974.99 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Poirel L, Brinas L, Fortineau N, Nordmann P: Integron-encoded GES-type extended-spectrum beta-lactamase with increased activity toward aztreonam in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005 Aug;49(8):3593-7. [PubMed:16048994 ]
  4. Diaz N, Suarez D, Sordo TL: Molecular dynamics simulations of class C beta-lactamase from Citrobacter freundii: insights into the base catalyst for acylation. Biochemistry. 2006 Jan 17;45(2):439-51. [PubMed:16401074 ]
  5. Mirelis B, Rivera A, Miro E, Mesa RJ, Navarro F, Coll P: A simple phenotypic method for differentiation between acquired and chromosomal AmpC beta-lactamases in Escherichia coli. Enferm Infecc Microbiol Clin. 2006 Jun-Jul;24(6):370-2. [PubMed:16792938 ]
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Drug created on June 13, 2005 07:24 / Updated on May 25, 2016 02:17