Aztreonam Explained

Verifiedrevid:458976305
Width:150
Tradename:Azactam, Cayston, others
Pregnancy Au:B1
Routes Of Administration:Intravenous, intramuscular, inhalation
Atc Prefix:J01
Atc Suffix:DF01
Legal Uk:POM
Legal Us:Rx-only
Legal Eu:Rx-only
Legal Eu Comment:[1]
Bioavailability:100% (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
Cas Number:78110-38-0
Pubchem:5742832
Drugbank:DB00355
Chemspiderid:4674940
Unii:G2B4VE5GH8
Kegg:D00240
Chebi:161680
Chembl:158
Iupac Name:2-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: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:WZPBZJONDBGPKJ-VEHQQRBSSA-N
Melting Point:227
Melting Notes:(dec.)

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.[2] This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.

Common side effects when given by injection include pain at the site of injection, vomiting, and rash. Common side effects when inhaled include wheezing, cough, and vomiting. Serious side effects include Clostridium difficile infection and allergic reactions including anaphylaxis. Those who are allergic to other β-lactam have a low rate of allergy to aztreonam. Use in pregnancy appears to be safe. It is in the monobactam family of medications. Aztreonam inhibits cell wall synthesis by blocking peptidoglycan crosslinking to cause bacterial death.

Aztreonam was approved for medical use in the United States in 1986.[3] It was removed from the World Health Organization's List of Essential Medicines in 2019.[4] [5] It is available as a generic medication.[3] It is a manufactured version of a chemical from the bacterium Chromobacterium violaceum.[6] 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 Europe 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.[7]

Aztreonam has strong activity against susceptible gram-negative bacteria, including Pseudomonas aeruginosa. It is resistant to some beta-lactamases, but is inactivated by extended-spectrum beta-lactamases.

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.[8] The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant microorganisms.[9]

Synergism between aztreonam and arbekacin or tobramycin against P. aeruginosa has been suggested.[10]

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.[11]

Aztreonam can be safely used in patients with a penicillin or cephalosporin allergy (except for patients with a ceftazidime allergy as ceftazidime and aztreonam share a similar side chain).[12] It is also frequently used as an alternative to aminoglycosides because is not ototoxic or nephrotoxic.[13]

Aztreonam is under consideration for human infections sustained by metallo-beta-lactamase (MBL)-producing Gram-negative bacteria. In these circumstances aztreonam is combined with avibactam (ceftazidime/avibactam). The combination of aztreonam and avibactam are in phase 3 clinical trails. 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.[14]

Administration

Aztreonam is poorly absorbed when given orally, 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 Food and Drug Administration (FDA) approved the inhalation form on 22 February 2010, for the suppression of P. aeruginosa infections in patients with cystic fibrosis.[15] It received conditional approval for administration in Canada and the European Union in September 2009, and has been fully approved in Australia.[16]

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.[17] 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 cephalosporins. 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.[18]

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 bacteria very poorly and is largely ineffective against them.[19] Aztreonam is bactericidal, but less so than some of the cephalosporins.

Notes and References

  1. Web site: Cayston EPAR . European Medicines Agency . 21 June 2004 . 12 July 2024.
  2. Book: British national formulary : BNF 69. 2015. British Medical Association. 9780857111562. 381. 69.
  3. Web site: Aztreonam. The American Society of Health-System Pharmacists. 8 December 2017.
  4. Book: ((World Health Organization)) . 2019 . 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 . World Health Organization . Geneva . World Health Organization . 10665/325773 . WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO . free .
  5. Book: ((World Health Organization)) . 2019 . 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) . World Health Organization . Geneva . World Health Organization . 10665/330668 . WHO technical report series;1021 . free . 9789241210300 . 0512-3054 .
  6. Book: Yaffe SJ, Aranda JV . Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice. 2010. Lippincott Williams & Wilkins. 9780781795388. 438.
  7. Quon BS, Goss CH, Ramsey BW . Inhaled antibiotics for lower airway infections . Annals of the American Thoracic Society . 11 . 3 . 425–34 . March 2014 . 24673698 . 4028738 . 10.1513/annalsats.201311-395fr .
  8. Book: Mosby's Drug Consult 2006 . Mosby, Inc. . 2006 . 16th.
  9. Web site: Aztreonam Susceptibility and Minimum Inhibitory Concentration (MIC) Data . 3 February 2020 . toku-e.com .
  10. Kobayashi Y, Uchida H, Kawakami Y . Synergy with aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa isolated from blood . The Journal of Antimicrobial Chemotherapy . 30 . 6 . 871–2 . December 1992 . 1289363 . 10.1093/jac/30.6.871 .
  11. Web site: Aztreonam spectrum of bacterial susceptibility and Resistance. https://web.archive.org/web/20140327063155/http://www.toku-e.com/Upload/Products/PDS/20120618004526.pdf . 27 March 2014 . 15 May 2012 . Product Data Sheet . toku-e.com .
  12. James CW, Gurk-Turner C . Cross-reactivity of beta-lactam antibiotics . Proceedings . 14 . 1 . 106–107 . January 2001 . 16369597 . 1291320 . 10.1080/08998280.2001.11927741 .
  13. Johnson DH, Cunha BA . 1995 . Aztreonam . Medical Clinics of North America . en . 79 . 4 . 733–743 . 10.1016/S0025-7125(16)30036-0. 7791420 . free .
  14. Mauri C, Maraolo AE, Di Bella S, Luzzaro F, Principe L . 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 . Antibiotics . 10 . 8 . 1012 . August 2021 . 34439062 . 8388901 . 10.3390/antibiotics10081012 . free .
  15. News: 22 February 2010 . Gilead's Inhaled Antibiotic for Lungs Wins Approval . Catherine L . BusinessWeek . 5 March 2010 . dead . https://web.archive.org/web/20100302011232/http://www.businessweek.com/news/2010-02-22/gilead-s-inhaled-antibiotic-for-lungs-wins-approval-update1-.html . 2 March 2010 .
  16. News: 23 February 2010 . FDA approves Gilead cystic fibrosis drug Cayston . https://web.archive.org/web/20100301043940/http://www.businessweek.com/ap/financialnews/D9E237QG1.htm . dead . 1 March 2010 . BusinessWeek . 5 March 2010.
  17. Di Bella S, Sanson G, Monticelli J, Zerbato V, Principe L, Giuffrè M, Pipitone G, Luzzati R . Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options . Clinical Microbiology Reviews . e0013523 . February 2024 . 37 . 2 . 38421181 . 10.1128/cmr.00135-23 . Staley C, Abhyankar M .
  18. Terico AT, Gallagher JC . Beta-lactam hypersensitivity and cross-reactivity . Journal of Pharmacy Practice . 27 . 6 . 530–544 . December 2014 . 25124380 . 10.1177/0897190014546109 . 19275020 . free .
  19. Book: AHFS Drug Information 2006 . American Society of Health-System Pharmacists . 2006 . 2006 .