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. 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. The following represents MIC susceptibility data for a few medically significant microorganisms.
Staphylococcus aureus 8 - >128 μg/ml
Staphylococcus epidermidis 8 - 32 μg/ml
Streptococcus pyogenes 8 - ≥128 μg/ml
Synergism between aztreonam and arbekacin or tobramycin against P. aeruginosa has been suggested.
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 diversus, Enterobacter agglomerans, Haemophilus spp. and Streptococcus pyogenes have developed resistance to aztreonam to varying degrees. Aztreonam is often used in people who are penicillin allergic or who cannot tolerate aminoglycosides.
Administration
Aztreonam is poorly absorbed when given orally, so it must be administered as an intravenous or intramuscular injection, or inhaled using an ultrasonic nebulizer. In the United States, the Food and Drug Administration approved the inhalation form on 22 February 2010, for the suppression of P. aeruginosa infections in patients with cystic fibrosis. It received conditional approval for administration in Canada and the European Unionin September 2009, and has been fully approved in Australia.
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. There may be drug-induced eosinophilia. Because of the unfused beta-lactam ring unique to aztreonam, 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 to penicillins and nearly all cephalosporins. However, like other beta lactams, there is a risk of very serious allergic reactions, including anaphylaxis. The aztreonam label directs physicians to be aware of the possibility of these severe adverse reactions. This is more likely if the patient is allergic to a certain cephalosporin known as ceftazidime. Aztreonam exhibits cross-reactivity with this cephalosporin due to a similar side chain. Physicians should evaluate prior allergy history when prescribing this medicine. Special caution is warranted in patients who are allergic to ceftazidime and are subsequently placed on aztreonam therapy.
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. Aztreonam is bactericidal, but less so than some of the cephalosporins.
