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| Clinical data | |
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| Trade names | Azactam, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a687010 |
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| Routes of administration | Intravenous,intramuscular,inhalation |
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| Pharmacokinetic data | |
| Bioavailability | 100% (IM) 0.1% (by mouth in rats) Unknown (by mouth in humans) |
| Protein binding | 56% |
| Metabolism | Liver (minor %) |
| Eliminationhalf-life | 1.7 hours |
| Excretion | Kidney |
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| ChEBI | |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.071.652 |
| Chemical and physical data | |
| Formula | C13H17N5O8S2 |
| Molar mass | 435.43 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 227 °C (441 °F) (dec.) |
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Aztreonam, sold under the brand nameAzactam among others, is anantibiotic used primarily to treat infections caused bygram-negative bacteria such asPseudomonas aeruginosa.[2][3] This may includebone infections,endometritis,intra abdominal infections,pneumonia,urinary tract infections, andsepsis.[2] It is given byintravenous orintramuscular injection or byinhalation.[2]
Common side effects when given by injection include pain at the site of injection, vomiting, and rash.[2] Common side effects when inhaled includewheezing, cough, and vomiting.[2] Serious side effects includeClostridioides difficile infection andallergic reactions includinganaphylaxis.[2] Those who are allergic to otherβ-lactam have a low rate of allergy to aztreonam.[2] Use inpregnancy appears to be safe.[2] It is in themonobactam family of medications.[2] Aztreonam inhibitscell wall synthesis by blockingpeptidoglycan crosslinking to causebacterial death.[2]
Aztreonam was approved for medical use in the United States in 1986.[2] It was removed from theWorld Health Organization's List of Essential Medicines in 2019.[4][5] It is available as ageneric medication.[2] It is a manufactured version of a chemical from the bacteriumChromobacterium violaceum.[6] Aztreonam is available in a combination with avibactam (aztreonam/avibactam).
Nebulized forms of aztreonam are used to treat infections that are complications ofcystic fibrosis and are approved for such use in the EU and the US; they are also used off-label fornon-CF bronchiectasis,ventilator-associated pneumonia,chronic obstructive pulmonary disease,mycobacterial disease, and to treat infections in people who have receivedlung transplants.[7]
Aztreonam has strong activity against susceptiblegram-negative bacteria, includingPseudomonas aeruginosa. It is resistant to somebeta-lactamases, but is inactivated byextended-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 includingCitrobacter,Enterobacter,E. coli,Haemophilus,Klebsiella,Proteus, andSerratia species.[8] The following representsminimum inhibitory concentration (MIC) susceptibility data for a few medically significant microorganisms.[9]
Acinetobacter anitratus,Escherichia coli,Pseudomonas aeruginosa, andProteus mirabilis are generally susceptible to aztreonam, while somestaphylococci,Staphylococcus aureus,Staphylococcus haemolyticus andXanthomonas maltophilia are resistant to it. Furthermore,Aeromonas hydrophila,Citrobacter koseri (Citrobacter diversus),Pantoea agglomerans (Enterobacter agglomerans),Haemophilus spp. andStreptococcus pyogenes have developed resistance to aztreonam to varying degrees.[10]
Aztreonam is poorly absorbed when given orally, so it must be administered as anintravenous orintramuscular injection (brand name Azactam), orinhaled (brand name Cayston) using an ultrasonic nebulizer. In the United States, theFood and Drug Administration (FDA) approved the inhalation form in February 2010, for the suppression ofP. aeruginosa infections in people withcystic fibrosis.[11] It received conditional approval for administration in Canada and the European Union in September 2009,[11] and has been fully approved in Australia.[12]
Aztreonam can be safely used in people with a penicillin or cephalosporin allergy (except for people with aceftazidime allergy as ceftazidime and aztreonam share a similar side chain).[13] It is also frequently used as an alternative toaminoglycosides because is not ototoxic or nephrotoxic.[14]
Reported side effects include injection site reactions,rash, and rarelytoxic epidermal necrolysis. Gastrointestinal side effects generally includediarrhea andnausea andvomiting. AlthoughC. difficile infection is a possible complication of aztreonam therapy, this antibiotic is associated with a low risk of developingC. difficile infection.[15] There may be drug-inducedeosinophilia. Because of the unfused beta-lactam ring there is somewhat lower cross-reactivity between aztreonam and many otherbeta-lactam antibiotics, and it may be safe to administer aztreonam to many patients with hypersensitivity (allergies) to penicillins and nearly allcephalosporins.[16] 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 toceftazidime, a cephalosporin. Aztreonam exhibits cross-sensitivity with ceftazidime due to a similar side chain.[17]
Aztreonam is similar in action topenicillin. It inhibits synthesis of the bacterial cell wall, by blockingpeptidoglycan crosslinking. It has a very high affinity forpenicillin-binding protein-3 and mild affinity for penicillin-binding protein-1a. Aztreonam binds the penicillin-binding proteins ofGram-positive andanaerobic bacteria very poorly and is largely ineffective against them.[16] Aztreonam is bactericidal, but less so than some of thecephalosporins.[medical citation needed]
Aztreonam is under consideration for human infections sustained by metallo-beta-lactamase (MBL)-producing gram-negative bacteria. In these circumstances aztreonam is combined withceftazidime/avibactam. The combination of aztreonam and avibactam are in phase III clinical trails.[18][19] 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.[20]
Synergism between aztreonam andarbekacin ortobramycin againstP. aeruginosa has been suggested.[21]
