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.[ It is given by intravenous or intramuscular injection or by inhalation.][
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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 Clostridioides difficile infection and allergic reactions including anaphylaxis.][ Those who are allergic to other beta-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 bactericidal.][
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Aztreonam was approved for medical use in the United States in 1986.[ It is a manufactured version of a chemical from the bacterium Chromobacterium violaceum.]
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.
Aztreonam has strong activity against susceptible gram-negative bacteria, including Pseudomonas aeruginosa. It is resistant to some , 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, Escherichia coli, Haemophilus, Klebsiella, Proteus, and Serratia species.
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Staphylococcus aureus 8 - >128 μg/ml
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Staphylococcus epidermidis 8 - 32 μg/ml
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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.
Administration
Aztreonam is poorly absorbed when given orally, so it must be administered as an intravenous or intramuscular injection (brand name Azactam), or nebulizer (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.
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).
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.
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.
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 trials.
A synergism between aztreonam and arbekacin or tobramycin against P. aeruginosa has been suggested.
