Aztreonam: Uses, Mechanism of action, Dosage and Side effects

Aztreonam (Azactam) is an antibiotic belonging to a class known as monocyclic beta-lactam antibiotics (Monobactams). Aztreonam is not affected by beta-lactamases, therefore, it is used in the treatment of gram-negative infections, especially of the meninges, bladder, and kidneys.

It is a manufactured version of a chemical from the bacterium Chromobacterium violaceum.

Its use of gram-positive organisms may lead to a superinfection.

Indications of Aztreonam

Aztreonam is primarily used to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. These infections may include bone infections, endometritis, intra-abdominal infections, pneumonia, urinary tract infections, and sepsis.

Nebulized forms of aztreonam are used to treat infections that are complications of cystic fibrosis; 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

Pharmacokinetics

Aztreonam has a poor absorption when administered orally, therefore it must be administered as an intravenous or intramuscular injection, or inhaled using an ultrasonic nebulizer.

Side effects of Aztreonam

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 (allergies) to penicillins and nearly all cephalosporins.

However, like other beta-lactams, there is a risk of very serious allergic reactions, including anaphylaxis.

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.

Special caution is warranted in patients who are allergic to ceftazidime and are subsequently placed on aztreonam therapy.

Some of the serious side effects include Clostridium difficile infection and allergic reactions including anaphylaxis. Patients who are allergic to other β-lactam have a low rate of allergy to aztreonam.

Use in pregnancy

The use of aztreonam in pregnancy appears to be safe.

Mechanism of action

It is in the monobactam family of medications. Aztreonam is similar in action to penicillin. It inhibits the 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.

Drug interactions

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 hemolyticus, 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.

Dosage of Aztreonam

Usual Adult Dose for Bacteremia is 2 g IV every 6 to 8 hours

Therapy should be continued for approximately 10 to 14 days, depending on the nature and severity of the infection.

Usual Adult Dose for Bacterial Infection

Moderately severe infections: 1 to 2 g IV or IM every 8 to 12 hours
Severe infections: 2 g IV every 6 to 8 hours (maximum, 8 g/day)

Usual Adult Dose for Cystic Fibrosis

Inhalation:

Initial dose: 75 mg via nebulizer over approximately 2 to 3 minutes 3 times a day for 28 days; doses should be at least 4 hours apart

Maintenance dose: Administer in alternating cycles of 28 days on and 28 days off.

For patients on multiple inhaled therapies, the following order of administration is recommended: bronchodilator, mucolytics, and lastly, aztreonam for inhalation.

Usual Adult Dose for Febrile Neutropenia

2 g IV every 6 to 8 hours

Therapy should be continued until the absolute neutrophil count is greater than 500/mm3 and no infection is found or until an adequate clinical response is achieved if a susceptible infection is found and the patient has been afebrile for at least 24 hours. Therapy for neutropenic patients is often required for up to 3 weeks.

Usual Adult Dose for Intraabdominal Infection and peritonitis