Identification

Name
Aztreonam
Accession Number
DB00355  (APRD00815, EXPT00605)
Type
Small Molecule
Groups
Approved
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
  • Aztreonam
  • Aztréonam
  • Aztreonamum
  • Primbactam
External IDs
Corus 1020 / SQ 26776 / SQ-26776 / UNII-XNM7LT65NP
Product Ingredients
IngredientUNIICASInChI Key
Aztreonam LysineXNM7LT65NP827611-49-4KPPBAEVZLDHCOK-JHBYREIPSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AzactamInjection, solution1 g/50mLIntravenousElan Pharmaceuticals2009-06-012012-02-04Us
AzactamInjection, powder, for solution1 g/1Intramuscular; IntravenousE.R. Squibb & Sons, L.L.C.2010-04-01Not applicableUs
AzactamInjection, powder, for solution1 g/1Intramuscular; IntravenousCardinal Health2009-06-012011-11-30Us
AzactamInjection, powder, for solution1 g/1Intramuscular; IntravenousElan Pharmaceuticals2009-06-012013-03-14Us
AzactamInjection, solution2 g/50mLIntravenousE.R. Squibb & Sons, L.L.C.2010-04-01Not applicableUs
AzactamInjection, solution2 g/50mLIntravenousElan Pharmaceuticals2009-06-012012-02-03Us
AzactamInjection, powder, for solution2 g/1Intramuscular; IntravenousE.R. Squibb & Sons, L.L.C.2010-04-01Not applicableUs
AzactamInjection, solution1 g/50mLIntravenousE.R. Squibb & Sons, L.L.C.2010-04-01Not applicableUs
AzactamInjection, powder, for solution2 g/1Intramuscular; IntravenousElan Pharmaceuticals2009-06-012013-03-14Us
CaystonPowder, for solution75 mgRespiratory (inhalation)Gilead Sciences2009-11-11Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AztreonamInjection, powder, lyophilized, for solution1 g/1Intramuscular; IntravenousFresenius Kabi USA, LLC2009-11-05Not applicableUs
AztreonamInjection, powder, lyophilized, for solution500 mg/1Intramuscular; IntravenousAPP Pharmaceuticals, LLC2009-11-052010-06-25Us
AztreonamInjection, powder, lyophilized, for solution2 g/1Intramuscular; IntravenousFresenius Kabi USA, LLC2009-11-05Not applicableUs
International/Other Brands
Azactam / Azenam (Aristo) / Aztram (Shanxi C & Y) / Aztreo (Zydus Cadila) / Bencipen (AC Farma) / Primbactam (Menarini) / Trezam (Glenmark) / Vebac (Fahrenheit)
Categories
UNII
G2B4VE5GH8
CAS number
78110-38-0
Weight
Average: 435.433
Monoisotopic: 435.051853925
Chemical Formula
C13H17N5O8S2
InChI Key
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[C@H]1[C@H](NC(=O)C(=N/OC(C)(C)C(=O)O)\C2=CSC([NH3+])=N2)C(=O)N1S([O-])(=O)=O

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Aztreonam 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 action

The 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.

TargetActionsOrganism
APenicillin-binding protein 3
inhibitor
Bacillus subtilis (strain 168)
ABeta-lactamase
potentiator
Citrobacter freundii
Absorption

Less than 1% absorbed from the gastrointestinal tract following oral administration. Completely absorbed following intramuscular administration.

Volume of distribution
  • 12.6 L
Protein binding

Serum 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 elimination

In 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 life

The 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]
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Aztreonam is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Aztreonam is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Aztreonam is combined with 4-hydroxycoumarin.
AbacavirAztreonam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Aztreonam which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Aztreonam which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Aztreonam which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Aztreonam is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Aztreonam which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Aztreonam which could result in a higher serum level.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0014499
KEGG Drug
D00240
KEGG Compound
C06840
PubChem Compound
9568617
PubChem Substance
46505419
ChemSpider
4674940
BindingDB
50240480
ChEBI
161680
ChEMBL
CHEMBL158
Therapeutic Targets Database
DAP000117
PharmGKB
PA448523
HET
AZR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Aztreonam
ATC Codes
J01DF01 — Aztreonam
AHFS Codes
  • 08:12.07.16 — Monobactams
FDA label
Download (1.57 MB)
MSDS
Download (42 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1CompletedBasic ScienceBacterial Infections / Complicated skin infection bacterial1
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentBacterial Infections1
2CompletedTreatmentBronchiectasis1
2CompletedTreatmentCystic Fibrosis (CF)1
2CompletedTreatmentCystic Fibrosis (CF) / Lung Infection / Pseudomonas Aeruginosa1
2Not Yet RecruitingTreatmentBronchiectasis Adult1
2RecruitingTreatmentCystic Fibrosis (CF)1
2TerminatedTreatmentOsteomyelitis1
3CompletedTreatmentBacterial Infections1
3CompletedTreatmentComplicated Skin and Soft Tissue Infection1
3CompletedTreatmentCystic Fibrosis (CF)2
3CompletedTreatmentCystic Fibrosis (CF) / Pseudomonas Aeruginosa1
3CompletedTreatmentSkin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections1
3CompletedTreatmentSkin and Subcutaneous Tissue Bacterial Infections1
3RecruitingTreatmentCystic Fibrosis (CF) / Pseudomonas aeruginosa respiratory tract infection1
3RecruitingTreatmentEnterobacteriaceae Infections1
3TerminatedTreatmentComplicated Skin and Soft Tissue Infection1
4Active Not RecruitingTreatmentCystic Fibrosis (CF) / Infection NOS / Pseudomonas Infections1
4Active Not RecruitingTreatmentInfection NOS1
4CompletedTreatmentComplication of Transplanted Lung1
Not AvailableActive Not RecruitingNot AvailablePseudomonas Aeruginosa in Cystic Fibrosis1
Not AvailableApproved for MarketingNot AvailableCystic Fibrosis (CF) / Pseudomonas Aeruginosa1
Not AvailableApproved for MarketingNot AvailableCystic Fibrosis (CF) / Pseudomonas Aeruginosa Airway Infection1
Not AvailableCompletedNot AvailableCystic Fibrosis (CF)1

Pharmacoeconomics

Manufacturers
  • Gilead sciences inc
  • Bristol myers squibb
  • Bristol myers squibb co
  • App pharmaceuticals llc
Packagers
  • APP Pharmaceuticals
  • Baxter International Inc.
  • Ben Venue Laboratories Inc.
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • E.R. Squibb and Sons LLC
  • Elan Pharmaceuticals Inc.
  • Gilead Sciences Inc.
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
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous500 mg/1
Kit75 mg/1mL
Powder, for solutionRespiratory (inhalation)75 mg
Powder, for suspensionRespiratory (inhalation)75 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)
CA1340253No1998-12-152015-12-15Canada
CA1338670No1996-10-222013-10-22Canada
US7208141No2007-04-242021-12-20Us
US7427633No2008-09-232021-12-20Us
US8399496No2013-03-192021-12-20Us
US7214364No2007-05-082021-12-20Us

Properties

State
Solid
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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Monobactams
Alternative Parents
N-acyl-alpha amino acids and derivatives / 2,4-disubstituted thiazoles / 2-amino-1,3-thiazoles / Heteroaromatic compounds / Organic sulfuric acids and derivatives / Secondary carboxylic acid amides / Amino acids / Azetidines / Carboxylic acids / Azacyclic compounds
show 7 more
Substituents
Monobactam / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / 2,4-disubstituted 1,3-thiazole / 1,3-thiazol-2-amine / Organic sulfuric acid or derivatives / Azole / Heteroaromatic compound / Thiazole / Amino acid or derivatives
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monobactam (CHEBI:161680) / Monobactams (C06840)

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
Uniprot Name
Penicillin-binding protein 3
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
Uniprot Name
Beta-lactamase
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]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:31