Editing Aztreonam

{{Short description|Chemical compound}}
{{Use dmy dates|date=April 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| verifiedrevid = 458976305
| image = Aztreonam skeletal structure.svg
| width = 250
| alt =
| image2 = Aztreonam ball-and-stick model from xtal 2023 inversion.png
| width2 = 250

<!-- Clinical data -->
| tradename = Azactam, others
| Drugs.com = {{drugs.com|monograph|aztreonam}}
| MedlinePlus = a687010
| pregnancy_AU = B1
| routes_of_administration = [[Intravenous therapy|Intravenous]], [[Intramuscular injection|intramuscular]], [[inhalation]]
| ATC_prefix = J01
| ATC_suffix = DF01
| ATC_supplemental = {{ATC|J01|DF51}}

| legal_UK = POM
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | title=Cayston EPAR | website=European Medicines Agency | date=21 June 2004 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/cayston | access-date=12 July 2024}}</ref>

<!-- Pharmacokinetic data -->
| bioavailability = 100% ([[Intramuscular injection|IM]]) 0.1% (by mouth in rats) Unknown (by mouth in humans)
| protein_bound = 56%
| metabolism = [[Liver]] (minor %)
| elimination_half-life = 1.7 hours
| excretion = [[Kidney]]

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 78110-38-0
| PubChem = 5742832
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00355
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4674940
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = G2B4VE5GH8
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00240
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 161680
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 158

<!-- Chemical data -->
| IUPAC_name = 2-<nowiki/>{[(1''Z'')-1-(2-Amino-1,3-thiazol-4-yl)-2-<nowiki/>{[(2''S'',3''S'')-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino}-2-oxoethylidene]amino}oxy-2-methylpropanoic acid
| C=13 | H=17 | N=5 | O=8 | S=2
| smiles = O=S(=O)(O)N2C(=O)[C@@H](NC(=O)C(=N\OC(C(=O)O)(C)C)/c1nc(sc1)N)[C@@H]2C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WZPBZJONDBGPKJ-VEHQQRBSSA-N
| melting_point = 227
| melting_notes = (dec.)
}}

<!-- Definition and medical uses -->
'''Aztreonam''', sold under the brand name '''Azactam''' among others, is an [[antibiotic]] used primarily to treat infections caused by [[gram-negative bacteria]] such as ''[[Pseudomonas aeruginosa]]''.<ref name=AHFS2017/><ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=381|edition=69}}</ref> This may include [[bone infections]], [[endometritis]], [[intra abdominal infections]], [[pneumonia]], [[urinary tract infections]], and [[sepsis]].<ref name=AHFS2017/> It is given by [[intravenous]] or [[intramuscular]] injection or by [[inhalation]].<ref name=AHFS2017/>

<!-- Side effects and mechanism -->
Common side effects when given by injection include pain at the site of injection, vomiting, and rash.<ref name=AHFS2017/> Common side effects when inhaled include [[wheezing]], cough, and vomiting.<ref name=AHFS2017/> Serious side effects include [[Clostridioides difficile infection|''Clostridioides difficile'' infection]] and [[allergic reactions]] including [[anaphylaxis]].<ref name=AHFS2017/> Those who are allergic to other [[beta-lactam|β-lactam]] have a low rate of allergy to aztreonam.<ref name=AHFS2017/> Use in [[pregnancy]] appears to be safe.<ref name=AHFS2017/> It is in the [[monobactam]] family of medications.<ref name=AHFS2017/> Aztreonam inhibits [[cell wall]] synthesis by blocking [[peptidoglycan]] crosslinking to cause [[bactericidal|bacterial death]].<ref name=AHFS2017/>

<!-- History and culture -->
Aztreonam was approved for medical use in the United States in 1986.<ref name=AHFS2017>{{cite web|title=Aztreonam|url=https://www.drugs.com/monograph/aztreonam.html|publisher=The American Society of Health-System Pharmacists|access-date= 8 December 2017}}</ref> It was removed from the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]] in 2019.<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | year = 2019 | title = Executive summary: the selection and use of essential medicines 2019: report of the 22nd WHO Expert Committee on the selection and use of essential medicines | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/325773 | id = WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref>{{cite book | vauthors = ((World Health Organization)) | year = 2019 | title = The selection and use of essential medicines: report of the WHO Expert Committee on Selection and Use of Essential Medicines, 2019 (including the 21st WHO Model List of Essential Medicines and the 7th WHO Model List of Essential Medicines for Children) | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/330668 | id = WHO technical report series;1021 | hdl-access=free | isbn = 9789241210300 | issn = 0512-3054 }}</ref>  It is available as a [[generic medication]].<ref name=AHFS2017/> It is a manufactured version of a chemical from the bacterium ''[[Chromobacterium violaceum]]''.<ref>{{cite book| vauthors = Yaffe SJ, Aranda JV |title=Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice|date=2010|publisher=Lippincott Williams & Wilkins|isbn=9780781795388|page=438|url=https://books.google.com/books?id=1e2-yggGeUIC&pg=PA438 }}</ref> Aztreonam is available in a combination with avibactam ([[aztreonam/avibactam]]).

== Medical uses ==
Nebulized forms of aztreonam are used to treat infections that are complications of [[cystic fibrosis]] and are approved for such use in the EU and the US; they are also used off-label for [[non-CF bronchiectasis]], [[ventilator-associated pneumonia]], [[chronic obstructive pulmonary disease]], [[mycobacterial disease]], and to treat infections in people who have received [[lung transplants]].<ref>{{cite journal | vauthors = Quon BS, Goss CH, Ramsey BW | title = Inhaled antibiotics for lower airway infections | journal = Annals of the American Thoracic Society | volume = 11 | issue = 3 | pages = 425–34 | date = March 2014 | pmid = 24673698 | pmc = 4028738 | doi = 10.1513/annalsats.201311-395fr }}</ref>

Aztreonam has strong activity against susceptible [[gram-negative bacteria]], including ''[[Pseudomonas aeruginosa]]''. It is resistant to some [[beta-lactamase]]s, but is inactivated by [[Beta-lactamase#Extended-spectrum beta-lactamase (ESBL)|extended-spectrum beta-lactamases]].{{cn|date=March 2023}}

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]]'', ''[[Escherichia coli|E. coli]]'', ''[[Haemophilus]]'', ''[[Klebsiella]]'', ''[[Proteus (bacterium)|Proteus]]'', and ''[[Serratia]]'' species.<ref name="Mosby">{{cite book | title=Mosby's Drug Consult 2006 | publisher= Mosby, Inc. | date= 2006 | edition= 16th}}</ref> The following represents [[minimum inhibitory concentration]] (MIC) susceptibility data for a few medically significant microorganisms.<ref>{{cite web | title = Aztreonam Susceptibility and Minimum Inhibitory Concentration (MIC) Data | date = 3 February 2020 | url = http://www.toku-e.com/Assets/MIC/Aztreonam.pdf | work = toku-e.com }}</ref>
* ''Staphylococcus aureus'' 8 - >128 μg/ml
* ''Staphylococcus epidermidis'' 8 - 32 μg/ml
* ''Streptococcus pyogenes'' 8 - ≥128 μg/ml

=== Spectrum of activity ===
''Acinetobacter anitratus'', ''[[Escherichia coli]]'', ''[[Pseudomonas aeruginosa]]'', and ''[[Proteus mirabilis]]'' are generally susceptible to aztreonam, while some [[staphylococci]], ''[[Staphylococcus aureus]]'', ''Staphylococcus haemolyticus'' and ''[[Xanthomonas maltophilia]]'' are resistant to it. Furthermore, ''[[Aeromonas hydrophila]]'', ''[[Citrobacter koseri]]'' (''Citrobacter diversus''), ''[[Pantoea agglomerans]]'' (''Enterobacter agglomerans''), ''[[Haemophilus]]'' spp. and ''[[Streptococcus pyogenes]]'' have developed resistance to aztreonam to varying degrees.<ref>{{cite web|title=Aztreonam spectrum of bacterial susceptibility and Resistance|url=http://www.toku-e.com/Upload/Products/PDS/20120618004526.pdf | archive-url = https://web.archive.org/web/20140327063155/http://www.toku-e.com/Upload/Products/PDS/20120618004526.pdf | archive-date = 27 March 2014 |access-date=15 May 2012 | work = Product Data Sheet | publisher = toku-e.com }}</ref>

=== Administration ===
Aztreonam is poorly absorbed when given orally, so it must be administered as an [[intravenous]] or [[intramuscular]] injection (brand name Azactam), or [[nebulizer|inhaled]] (brand name Cayston) using an ultrasonic nebulizer. In the United States, the [[Food and Drug Administration]] (FDA) approved the inhalation form in February 2010, for the suppression of ''P. aeruginosa'' infections in people with [[cystic fibrosis]].<ref name="BW1">{{cite news|date=22 February 2010 |title=Gilead's Inhaled Antibiotic for Lungs Wins Approval |url=http://www.businessweek.com/news/2010-02-22/gilead-s-inhaled-antibiotic-for-lungs-wins-approval-update1-.html | vauthors = Catherine L |work=BusinessWeek |access-date=5 March 2010 |url-status=dead |archive-url=https://web.archive.org/web/20100302011232/http://www.businessweek.com/news/2010-02-22/gilead-s-inhaled-antibiotic-for-lungs-wins-approval-update1-.html |archive-date=2 March 2010 }}</ref> It received conditional approval for administration in Canada and the European Union in September 2009,<ref name="BW1" /> and has been fully approved in Australia.<ref>{{cite news|date=23 February 2010 |title=FDA approves Gilead cystic fibrosis drug Cayston |url=http://www.businessweek.com/ap/financialnews/D9E237QG1.htm |archive-url=https://web.archive.org/web/20100301043940/http://www.businessweek.com/ap/financialnews/D9E237QG1.htm |url-status=dead |archive-date=1 March 2010 |work=BusinessWeek |access-date=5 March 2010}}</ref>

== Contraindications ==
Aztreonam can be safely used in people with a penicillin or cephalosporin allergy (except for people with a [[ceftazidime]] allergy as ceftazidime and aztreonam share a similar side chain).<ref>{{cite journal | vauthors = James CW, Gurk-Turner C | title = Cross-reactivity of beta-lactam antibiotics | journal = Proceedings | volume = 14 | issue = 1 | pages = 106–107 | date = January 2001 | pmid = 16369597 | pmc = 1291320 | doi = 10.1080/08998280.2001.11927741 }}</ref> It is also frequently used as an alternative to [[aminoglycoside]]s because is not ototoxic or nephrotoxic.<ref>{{Cite journal | vauthors = Johnson DH, Cunha BA |date=1995 |title=Aztreonam |journal=Medical Clinics of North America |volume=79 |issue=4 |pages=733–743 |doi=10.1016/S0025-7125(16)30036-0|pmid=7791420 |doi-access=free }}</ref>

== Side effects ==
Reported side effects include injection site reactions, [[rash]], and rarely [[toxic epidermal necrolysis]]. Gastrointestinal side effects generally include [[diarrhea]] and [[nausea]] and [[vomiting]]. Although ''C. difficile'' infection is a possible complication of aztreonam therapy, this antibiotic is associated with a low risk of developing ''C. difficile'' infection.<ref>{{cite journal | vauthors = Di Bella S, Sanson G, Monticelli J, Zerbato V, Principe L, Giuffrè M, Pipitone G, Luzzati R | title = ''Clostridioides difficile'' infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options | journal = Clinical Microbiology Reviews | pages = e0013523 | date = February 2024 | volume = 37 | issue = 2 | pmid = 38421181 | doi = 10.1128/cmr.00135-23 | pmc = 11324037 | veditors = Staley C, Abhyankar M }}</ref> There may be drug-induced [[eosinophilia]]. Because of the unfused beta-lactam ring there is somewhat lower cross-reactivity between aztreonam and many other [[beta-lactam]] antibiotics, and it may be safe to administer aztreonam to many patients with hypersensitivity (allergies) to penicillins and nearly all [[cephalosporin]]s.<ref name="AHFS" /> There is a much lower risk of cross-sensitivity between aztreonam and other beta-lactam antibiotics than within other beta-lactam antibiotics. However, there is a higher chance of cross-sensitivity if a person is specifically allergic to [[ceftazidime]], a cephalosporin. Aztreonam exhibits cross-sensitivity with ceftazidime due to a similar side chain.<ref name="JPP2014">{{cite journal | vauthors = Terico AT, Gallagher JC | title = Beta-lactam hypersensitivity and cross-reactivity | journal = Journal of Pharmacy Practice | volume = 27 | issue = 6 | pages = 530–544 | date = December 2014 | pmid = 25124380 | doi = 10.1177/0897190014546109 | s2cid = 19275020 | doi-access = free }}</ref>

== Mechanism of action ==
Aztreonam is similar in action to [[penicillin]]. It inhibits synthesis of the bacterial cell wall, by 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 organism|anaerobic]] bacteria very poorly and is largely ineffective against them.<ref name="AHFS">{{cite book | title= AHFS Drug Information 2006 | publisher= American Society of Health-System Pharmacists | date= 2006 | edition= 2006 }}</ref> Aztreonam is bactericidal, but less so than some of the [[cephalosporins]].{{medcn|date=September 2019}}

== Research ==
Aztreonam is under consideration for human infections sustained by metallo-beta-lactamase (MBL)-producing gram-negative bacteria. In these circumstances aztreonam is combined with [[ceftazidime/avibactam]]. The combination of aztreonam and avibactam are in phase III clinical trails.<ref>{{ClinicalTrialsGov|NCT03329092|A Study to Determine the Efficacy, Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem (MER) ± Colistin (COL) for the Treatment of Serious Infections Due to Gram Negative Bacteria. (REVISIT)}}</ref><ref>{{ClinicalTrialsGov|NCT03580044|Efficacy, Safety, and Tolerability of ATM-AVI in the Treatment of Serious Infection Due to MBL-producing Gram-negative Bacteria}}</ref> The combination of aztreonam and avibactam has demonstrated to be active against 80% of MBL isolates reaching a clinical infection resolution in 80% of MBL-infected patients.<ref>{{cite journal | vauthors = Mauri C, Maraolo AE, Di Bella S, Luzzaro F, Principe L | title = The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases | journal = Antibiotics | volume = 10 | issue = 8 | pages = 1012 | date = August 2021 | pmid = 34439062 | pmc = 8388901 | doi = 10.3390/antibiotics10081012 | doi-access = free }}</ref>

Synergism between aztreonam and [[arbekacin]] or [[tobramycin]] against ''P. aeruginosa'' has been suggested.<ref>{{cite journal | vauthors = Kobayashi Y, Uchida H, Kawakami Y | title = Synergy with aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa isolated from blood | journal = The Journal of Antimicrobial Chemotherapy | volume = 30 | issue = 6 | pages = 871–2 | date = December 1992 | pmid = 1289363 | doi = 10.1093/jac/30.6.871 }}</ref>

== References ==
{{reflist}}

{{Cell wall disruptive antibiotics}}
{{Portal bar | Medicine}}
{{Authority control}}

[[Category:Drugs developed by Bristol Myers Squibb]]
[[Category:Conjugated ketones]]
[[Category:Enantiopure drugs]]
[[Category:Monobactam antibiotics]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Sulfamates]]
[[Category:Thiazoles]]
[[Category:Ketoxime ethers]]