Aztreonam

Last updated

Aztreonam
Aztreonam structure.svg
Clinical data
Trade names Azactam, Cayston, others
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU:B1
Routes of
administration 		Intravenous, intramuscular, inhalation
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 100% (IM) 0.1% (by mouth in rats) Unknown (by mouth in humans)
Protein binding 56%
Metabolism Liver (minor %)
Elimination half-life 1.7 hours
Excretion Kidney
Identifiers
  • 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
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.071.652 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C13H17N5O8S2
Molar mass 435.43 g·mol−1
3D model (JSmol)
Melting point 227 °C (441 °F) (dec.)
  • O=S(=O)(O)N2C(=O)[C@@H](NC(=O)C(=N\OC(C(=O)O)(C)C)/c1nc(sc1)N)[C@@H]2C
  • 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 Yes check.svgY
  • Key:WZPBZJONDBGPKJ-VEHQQRBSSA-N Yes check.svgY
   (verify)

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

Contents

Common side effects when given by injection include pain at the site of injection, vomiting, and rash. [2] Common side effects when inhaled include wheezing, cough, and vomiting. [2] Serious side effects include Clostridioides difficile infection and allergic reactions including anaphylaxis. [2] Those who are allergic to other β-lactam have a low rate of allergy to aztreonam. [2] Use in pregnancy appears to be safe. [2] It is in the monobactam family of medications. [2] Aztreonam inhibits cell wall synthesis by blocking peptidoglycan crosslinking to cause bacterial death. [2]

Aztreonam was approved for medical use in the United States in 1986. [2] It was removed from the World Health Organization's List of Essential Medicines in 2019. [4] [5] It is available as a generic medication. [2] 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.[ citation needed ]

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. [14] [15] 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. [16]

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. [17] It received conditional approval for administration in Canada and the European Union in September 2009, [17] and has been fully approved in Australia. [18]

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. [19] 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. [20] 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. [21]

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. [20] Aztreonam is bactericidal, but less so than some of the cephalosporins.[ medical citation needed ]

Related Research Articles

<span class="mw-page-title-main">Beta-lactamase</span> Class of enzymes

Beta-lactamases (β-lactamases) are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.

<span class="mw-page-title-main">Penicillin</span> Group of antibiotics derived from Penicillium fungi

Penicillins are a group of β-lactam antibiotics originally obtained from Penicillium moulds, principally P. chrysogenum and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G and penicillin V. Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for various bacterial infections, though many types of bacteria have developed resistance following extensive use.

<span class="mw-page-title-main">Cephalosporin</span> Class of pharmaceutical drugs

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

<span class="mw-page-title-main">Cefazolin</span> Antibiotic medication

Cefazolin, also known as cefazoline and cephazolin, is a first-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. Specifically it is used to treat cellulitis, urinary tract infections, pneumonia, endocarditis, joint infection, and biliary tract infections. It is also used to prevent group B streptococcal disease around the time of delivery and before surgery. It is typically given by injection into a muscle or vein.

<span class="mw-page-title-main">Ceftriaxone</span> Antibiotic medication

Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint infections, intra-abdominal infections, skin infections, urinary tract infections, gonorrhea, and pelvic inflammatory disease. It is also sometimes used before surgery and following a bite wound to try to prevent infection. Ceftriaxone can be given by injection into a vein or into a muscle.

<span class="mw-page-title-main">Amoxicillin/clavulanic acid</span> Combination antibiotic medication

Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. It is specifically used for otitis media, streptococcal pharyngitis, pneumonia, cellulitis, urinary tract infections, and animal bites. It is taken by mouth or by injection into a vein.

<span class="mw-page-title-main">Ceftazidime</span> Antibiotic medication

Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, urinary tract infections, malignant otitis externa, Pseudomonas aeruginosa infection, and vibrio infection. It is given by injection into a vein, muscle, or eye.

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta-lactam antibiotics drug class, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Cefepime</span> Fourth-generation Cephalosporin Antibiotic

Cefepime is a fourth-generation cephalosporin antibiotic. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both types of organism than third-generation agents. A 2007 meta-analysis suggested when data of trials were combined, mortality was increased in people treated with cefepime compared with other β-lactam antibiotics. In response, the U.S. Food and Drug Administration (FDA) performed their own meta-analysis which found no mortality difference.

<span class="mw-page-title-main">Cefotaxime</span> Chemical compound

Cefotaxime is an antibiotic used to treat several bacterial infections in humans, other animals, and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.

<span class="mw-page-title-main">Cefotiam</span> Chemical compound

Cefotiam is a parenteral third-generation cephalosporin antibiotic. It has broad-spectrum activity against Gram-positive and Gram-negative bacteria. As a beta-lactam, its bactericidal activity results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins.

β-Lactamase inhibitor Drugs that inhibit β-Lactamase enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

<span class="mw-page-title-main">Ceftaroline fosamil</span> Chemical compound

Ceftaroline fosamil (INN), brand name Teflaro in the US and Zinforo in Europe, is a cephalosporin antibiotic with anti-MRSA activity. Ceftaroline fosamil is a prodrug of ceftaroline. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria. It retains some activity of later-generation cephalosporins having broad-spectrum activity against Gram-negative bacteria, but its effectiveness is relatively much weaker. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.

Cephalosporins are a broad class of bactericidal antibiotics that include the β-lactam ring and share a structural similarity and mechanism of action with other β-lactam antibiotics. The cephalosporins have the ability to kill bacteria by inhibiting essential steps in the bacterial cell wall synthesis which in the end results in osmotic lysis and death of the bacterial cell. Cephalosporins are widely used antibiotics because of their clinical efficiency and desirable safety profile.

<span class="mw-page-title-main">Avibactam</span> Chemical compound

Avibactam is a non-β-lactam β-lactamase inhibitor developed by Actavis jointly with AstraZeneca. A new drug application for avibactam in combination with ceftazidime was approved by the FDA on February 25, 2015, for treating complicated urinary tract (cUTI) and complicated intra-abdominal infections (cIAI) caused by antibiotic resistant-pathogens, including those caused by multi-drug resistant Gram-negative bacterial pathogens.

<span class="mw-page-title-main">Ceftolozane/tazobactam</span> Antibiotic

Ceftolozane/tazobactam, sold under the brand name Zerbaxa, is a fixed-dose combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults. Ceftolozane is a cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that are resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia.

<span class="mw-page-title-main">Ceftazidime/avibactam</span> Combination antibiotic medication

Ceftazidime/avibactam, sold under the brand name Avycaz among others, is a fixed-dose combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor. It is used to treat complicated intra-abdominal infections, urinary tract infections, and pneumonia. It is only recommended when other options are not appropriate. It is given by infusion into a vein.

Meropenem/vaborbactam, sold under the brand name Vabomere among others, is a combination medication used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia. It contains meropenem, a beta-lactam antibiotic, and vaborbactam, a beta-lactamase inhibitor. It is given by injection into a vein.

References

  1. ↑ "Cayston EPAR". European Medicines Agency. 21 June 2004. Retrieved 12 July 2024.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 "Aztreonam". The American Society of Health-System Pharmacists. Retrieved 8 December 2017.
  3. ↑ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 381. ISBN   9780857111562.
  4. ↑ 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. Geneva: World Health Organization. hdl: 10665/325773 . WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO.
  5. ↑ 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). Geneva: World Health Organization. hdl: 10665/330668 . ISBN   9789241210300. ISSN   0512-3054. WHO technical report series;1021.
  6. ↑ Yaffe SJ, Aranda JV (2010). Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice. Lippincott Williams & Wilkins. p. 438. ISBN   9780781795388.
  7. ↑ Quon BS, Goss CH, Ramsey BW (March 2014). "Inhaled antibiotics for lower airway infections". Annals of the American Thoracic Society. 11 (3): 425–34. doi:10.1513/annalsats.201311-395fr. PMC   4028738 . PMID   24673698.
  8. ↑ Mosby's Drug Consult 2006 (16th ed.). Mosby, Inc. 2006.
  9. ↑ "Aztreonam Susceptibility and Minimum Inhibitory Concentration (MIC) Data" (PDF). toku-e.com. 3 February 2020.
  10. ↑ Kobayashi Y, Uchida H, Kawakami Y (December 1992). "Synergy with aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa isolated from blood". The Journal of Antimicrobial Chemotherapy. 30 (6): 871–2. doi:10.1093/jac/30.6.871. PMID   1289363.
  11. ↑ "Aztreonam spectrum of bacterial susceptibility and Resistance" (PDF). Product Data Sheet. toku-e.com. Archived from the original (PDF) on 27 March 2014. Retrieved 15 May 2012.
  12. ↑ James CW, Gurk-Turner C (January 2001). "Cross-reactivity of beta-lactam antibiotics". Proceedings. 14 (1): 106–107. doi:10.1080/08998280.2001.11927741. PMC   1291320 . PMID   16369597.
  13. ↑ Johnson DH, Cunha BA (1995). "Aztreonam". Medical Clinics of North America. 79 (4): 733–743. doi: 10.1016/S0025-7125(16)30036-0 . PMID   7791420.
  14. ↑ Clinical trial number NCT03329092 for "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)" at ClinicalTrials.gov
  15. ↑ Clinical trial number NCT03580044 for "Efficacy, Safety, and Tolerability of ATM-AVI in the Treatment of Serious Infection Due to MBL-producing Gram-negative Bacteria" at ClinicalTrials.gov
  16. ↑ Mauri C, Maraolo AE, Di Bella S, Luzzaro F, Principe L (August 2021). "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. doi: 10.3390/antibiotics10081012 . PMC   8388901 . PMID   34439062.
  17. 1 2 Catherine L (22 February 2010). "Gilead's Inhaled Antibiotic for Lungs Wins Approval". BusinessWeek. Archived from the original on 2 March 2010. Retrieved 5 March 2010.
  18. ↑ "FDA approves Gilead cystic fibrosis drug Cayston". BusinessWeek. 23 February 2010. Archived from the original on 1 March 2010. Retrieved 5 March 2010.
  19. ↑ Di Bella S, Sanson G, Monticelli J, Zerbato V, Principe L, Giuffrè M, et al. (February 2024). Staley C, Abhyankar M (eds.). "Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options". Clinical Microbiology Reviews. 37 (2): e0013523. doi:10.1128/cmr.00135-23. PMC  11324037. PMID   38421181.
  20. 1 2 AHFS Drug Information 2006 (2006 ed.). American Society of Health-System Pharmacists. 2006.
  21. ↑ Terico AT, Gallagher JC (December 2014). "Beta-lactam hypersensitivity and cross-reactivity". Journal of Pharmacy Practice. 27 (6): 530–544. doi: 10.1177/0897190014546109 . PMID   25124380. S2CID   19275020.
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