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

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 β-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 bacterial death.

Aztreonam was approved for medical use in the United States in 1986. It was removed from the World Health Organization's List of Essential Medicines in 2019. It is available as a generic medication. It is a manufactured version of a chemical from the bacterium Chromobacterium violaceum. Aztreonam is available in a combination with avibactam (aztreonam/avibactam).

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 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. The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant microorganisms.

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.

Aztreonam is poorly absorbed when given orally, so it must be administered as an intravenous or intramuscular injection (brand name Azactam), or inhaled (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. It received conditional approval for administration in Canada and the European Union in September 2009, and has been fully approved in Australia.