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2-[(Z)-[1-(2-Amino-1,3-thiazol-4-yl)-2-[[(2R,3R)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid

PubChem CID
22842006
Structure
2-[(Z)-[1-(2-Amino-1,3-thiazol-4-yl)-2-[[(2R,3R)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid_small.png
2-[(Z)-[1-(2-Amino-1,3-thiazol-4-yl)-2-[[(2R,3R)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid_3D_Structure.png
Molecular Formula
Synonyms
  • aztreonam
  • 2-[(Z)-[1-(2-Amino-1,3-thiazol-4-yl)-2-[[(2R,3R)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid
  • 78110-38-0
  • SCHEMBL9424655
Molecular Weight
435.4 g/mol
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Dates
  • Create:
    2007-12-05
  • Modify:
    2024-12-28
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.
Aztreonam is a parenterally administered, synthetic monobactam antibiotic that is specifically active against aerobic gram-negative bacilli is resistant to many beta-lactamases. Aztreonam therapy is often accompanied by mild, asymptomatic elevations in serum aminotransferase levels, but it has not been reported to cause clinically apparent liver injury.
Aztreonam is a monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum with bactericidal activity. Aztreonam preferentially binds to and inactivates penicillin-binding protein-3 (PBP-3), which is involved in bacterial cell wall synthesis, thereby inhibiting bacterial cell wall integrity and leading to cell lysis and death. This agent differs from other beta-lactam antibiotics because it is resistant to beta-lactamase hydrolysis, and it is usually used to treat infections caused by gram-negative aerobic microorganisms.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
2-[(Z)-[1-(2-Amino-1,3-thiazol-4-yl)-2-[[(2R,3R)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2R,3R)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.05.07)

2.1.2 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-/m1/s1
Computed by InChI 1.0.6 (PubChem release 2021.05.07)

2.1.3 InChIKey

WZPBZJONDBGPKJ-NACOFCMISA-N
Computed by InChI 1.0.6 (PubChem release 2021.05.07)

2.1.4 SMILES

C[C@@H]1[C@H](C(=O)N1S(=O)(=O)O)NC(=O)/C(=N\OC(C)(C)C(=O)O)/C2=CSC(=N2)N
Computed by OEChem 2.3.0 (PubChem release 2021.05.07)

2.2 Molecular Formula

C13H17N5O8S2
Computed by PubChem 2.1 (PubChem release 2021.05.07)

2.3 Other Identifiers

2.3.1 CAS

78110-38-0

2.3.2 European Community (EC) Number

2.3.3 DrugBank ID

2.3.4 Metabolomics Workbench ID

2.3.5 NCI Thesaurus Code

2.3.6 RXCUI

2.3.7 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Az threonam
  • Az-threonam
  • Azactam
  • Azthreonam
  • Aztreonam
  • SQ 26,776
  • SQ-26,776
  • SQ26,776
  • Urobactam

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
435.4 g/mol
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
XLogP3-AA
Property Value
0.3
Reference
Computed by XLogP3 3.0 (PubChem release 2021.05.07)
Property Name
Hydrogen Bond Donor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Hydrogen Bond Acceptor Count
Property Value
12
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Rotatable Bond Count
Property Value
7
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Exact Mass
Property Value
435.05185486 Da
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
Monoisotopic Mass
Property Value
435.05185486 Da
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
Topological Polar Surface Area
Property Value
238Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Heavy Atom Count
Property Value
28
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
808
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
2
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2019.01.04)

3.2 Experimental Properties

3.2.1 Solubility

Insoluble

3.3 Chemical Classes

3.3.1 Drugs

3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Monobactams
Human drug -> Prescription; Discontinued; Active ingredient (AZTREONAM)
Human drugs -> Antibacterials for systemic use -> Human pharmacotherapeutic group -> EMA Drug Category
Paediatric drug

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug 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.
Cayston is indicated for the suppressive therapy of chronic pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF) aged 6 years and older. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

6.2 LiverTox Summary

Aztreonam is a parenterally administered, synthetic monobactam antibiotic that is specifically active against aerobic gram-negative bacilli is resistant to many beta-lactamases. Aztreonam therapy is often accompanied by mild, asymptomatic elevations in serum aminotransferase levels, but it has not been reported to cause clinically apparent liver injury.

6.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Monobactams
Antiinfective Agents

6.4 FDA Approved Drugs

6.5 FDA Orange Book

6.6 FDA National Drug Code Directory

6.7 Drug Labels

Drug and label
Active ingredient and drug

6.8 Clinical Trials

6.8.1 ClinicalTrials.gov

6.8.2 EU Clinical Trials Register

6.8.3 NIPH Clinical Trials Search of Japan

6.9 EMA Drug Information

1 of 3
View All
Medicine
Category
Human drugs
Therapeutic area
Cystic Fibrosis; Respiratory Tract Infections
Active Substance
aztreonam lysine
INN/Common name
aztreonam
Pharmacotherapeutic Classes
Antibacterials for systemic use
Status
This medicine is authorized for use in the European Union
Company
Gilead Sciences Ireland UC
Market Date
2009-09-21
2 of 3
View All
Type
Paediatric investigation
Active Substance
Therapeutic Area
Infectious diseases
Drug Form
Powder and solvent for nebuliser solution
Administration Route
Inhalation use
Decision Type
PM: decision on the application for modification of an agreed PIP
Decision Date
2020-12-21

7 Pharmacology and Biochemistry

7.1 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.

7.2 MeSH Pharmacological Classification

Anti-Bacterial Agents
Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

7.3 FDA Pharmacological Classification

Non-Proprietary Name
AZTREONAM
Pharmacological Classes
Monobactams [CS]; Monobactam Antibacterial [EPC]

7.4 ATC Code

J01DF01

J - Antiinfectives for systemic use

J01 - Antibacterials for systemic use

J01D - Other beta-lactam antibacterials

J01DF - Monobactams

J01DF01 - Aztreonam

7.5 Absorption, Distribution and Excretion

Absorption
Less than 1% absorbed from the gastrointestinal tract following oral administration. Completely absorbed following intramuscular administration.
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.
Volume of Distribution
12.6 L
Clearance
91 mL/min [healthy]

7.6 Metabolism / Metabolites

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

7.7 Biological 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).

7.8 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.

8 Use and Manufacturing

8.1 Uses

<b>Use (kg; approx.) in Germany (2009):</b> >10

<b>Consumption (g per capita; approx.) in Germany (2009):</b> 0.000122

<b>Excretion rate:</b> 0.87

<b>Calculated removal (%):</b> 8.8

8.1.1 Use Classification

Human drugs -> Antibacterials for systemic use -> Human pharmacotherapeutic group -> EMA Drug Category
Human Drugs -> EU pediatric investigation plans
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9 Safety and Hazards

9.1 Hazards Identification

9.1.1 GHS Classification

Note
Pictograms displayed are for 60% (3 of 5) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 40% (2 of 5) of reports.
Pictogram(s)
Irritant
Health Hazard
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H317 (20%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H334 (60%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]

H400 (40%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

Precautionary Statement Codes

P233, P260, P261, P271, P272, P273, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P391, P403, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 5 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 2 of 5 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 2 notifications provided by 3 of 5 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

9.1.2 Hazard Classes and Categories

Skin Sens. 1 (20%)

Resp. Sens. 1 (60%)

Aquatic Acute 1 (40%)

9.2 Regulatory Information

New Zealand EPA Inventory of Chemical Status
Propanoic acid, 2-[[(Z)-[1-(2-amino-4-thiazolyl)-2-[[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methyl-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

9.3 Other Safety Information

Chemical Assessment

IMAP assessments - Propanoic acid, 2-[[[1-(2-amino-4-thiazolyl)-2-[(2-methyl-4-oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylidene]amino]oxy]-2-methyl-, [2S-[2.alpha.,3.beta.(Z)]]-: Environment tier I assessment

IMAP assessments - Propanoic acid, 2-[[[1-(2-amino-4-thiazolyl)-2-[(2-methyl-4-oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylidene]amino]oxy]-2-methyl-, [2S-[2.alpha.,3.beta.(Z)]]-: Human health tier I assessment

10 Toxicity

10.1 Toxicological Information

10.1.1 Hepatotoxicity

Aztreonam has systemic toxicities that are similar to those of other beta lactam antibiotics, but it is unclear whether it can cause hepatic injury similar to that of the penicillins or cephalosporins. Asymptomatic serum aminotransferase elevations are common during high dose, intravenous aztreonam therapy (10% to 38%). The enzyme abnormalities are usually mild-to-moderate, asymptomatic, self-limited and not requiring drug discontinuation. Enzyme elevations occur slightly more commonly during aztreonam therapy than with other comparative antibiotics. Cases of frank liver injury and jaundice attributable to aztreonam must be extremely rare as no individual cases have been reported. For this reason, there is no data regarding the latency or pattern of the injury. Instances of marked aminotransferase elevations within 3 to 5 days of starting aztreonam have been reported, but these cases were without jaundice and resolved rapidly once the drug was stopped.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

10.1.2 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Limited information indicates that aztreonam produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with beta-lactams, but these effects have not been adequately evaluated. A task force respiratory experts from Europe, Australia and New Zealand found that inhaled tobramycin is compatible with breastfeeding. Aztreonam is acceptable in nursing mothers.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

10.1.3 Protein Binding

Serum protein binding averaged 56% and is independent of dose. Impaired renal function, 36 to 43%.

11 Literature

11.1 Consolidated References

11.2 NLM Curated PubMed Citations

11.3 Chemical Co-Occurrences in Literature

11.4 Chemical-Gene Co-Occurrences in Literature

11.5 Chemical-Disease Co-Occurrences in Literature

12 Patents

12.1 Depositor-Supplied Patent Identifiers

13 Interactions and Pathways

13.1 Chemical-Target Interactions

13.2 Drug-Drug Interactions

14 Classification

14.1 MeSH Tree

14.2 WHO ATC Classification System

14.3 UN GHS Classification

14.4 FDA Drug Type and Pharmacologic Classification

15 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    Propanoic acid, 2-[[[1-(2-amino-4-thiazolyl)-2-[(2-methyl-4-oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylidene]amino]oxy]-2-methyl-, [2S-[2.alpha.,3.beta.(Z)]]-
    https://services.industrialchemicals.gov.au/search-assessments/
  2. DrugBank
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    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  3. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  4. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
    Propanoic acid, 2-[[(Z)-[1-(2-amino-4-thiazolyl)-2-[[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methyl-
    https://www.epa.govt.nz/industry-areas/hazardous-substances/guidance-for-importers-and-manufacturers/hazardous-substances-databases/
  5. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  6. DailyMed
  7. LiverTox
  8. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  9. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  10. Drugs and Lactation Database (LactMed)
  11. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  12. EU Clinical Trials Register
  13. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  14. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  15. Metabolomics Workbench
  16. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  17. NIPH Clinical Trials Search of Japan
  18. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  19. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    AZTREONAM
  20. Wikipedia
  21. Medical Subject Headings (MeSH)
    LICENSE
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    https://www.nlm.nih.gov/copyright.html
  22. PubChem
  23. GHS Classification (UNECE)
CONTENTS