Aztreonam, sold under the brand name Azactam among others, is an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

used primarily to treat infections caused by

gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

such as ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

''. This may include bone infections, endometritis, intra abdominal infections,

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

, urinary tract infections, and

sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

. It is given by

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

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 Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

appears to be safe. It is in the monobactam family of medications. Aztreonam inhibits

cell wall A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

synthesis by blocking

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating ...

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).

Medical uses

Nebulized forms of aztreonam are used to treat infections that are complications of

cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...

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

, including ''

''. 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 minimum inhibitory concentration (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

Spectrum of activity

''Acinetobacter anitratus'', ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'', ''

'', and '' Proteus mirabilis'' are generally susceptible to aztreonam, while some staphylococci, ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...

'', ''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

or intramuscular injection (brand name Azactam), or inhaled (brand name Cayston) using an ultrasonic nebulizer. In the United States, the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) approved the inhalation form in February 2010, for the suppression of ''P. aeruginosa'' infections in people with

. It received conditional approval for administration in Canada and the European Union in September 2009, and has been fully approved in Australia.

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). It is also frequently used as an alternative to aminoglycosides because is not ototoxic or nephrotoxic.

Side effects

Reported side effects include injection site reactions, rash, and rarely toxic epidermal necrolysis. Gastrointestinal side effects generally include

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

. Although ''C. difficile'' infection is a possible complication of aztreonam therapy, this antibiotic is associated with a low risk of developing ''C. difficile'' infection. There may be drug-induced eosinophilia. Because of the unfused beta-lactam ring 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

cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus '' Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibio ...

s. 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 to ceftazidime, a cephalosporin. Aztreonam exhibits cross-sensitivity with ceftazidime due to a similar side chain.

Mechanism of action

Aztreonam is similar in action to

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

. It inhibits synthesis of the bacterial cell wall, by blocking

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 In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...

and anaerobic bacteria very poorly and is largely ineffective against them. Aztreonam is bactericidal, but less so than some of the

cephalosporins The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotic ...

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. 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. A synergism between aztreonam and arbekacin or tobramycin against ''P. aeruginosa'' has been suggested.

References

{{Authority control Drugs developed by Bristol Myers Squibb Conjugated ketones Enantiopure drugs Monobactam antibiotics Wikipedia medicine articles ready to translate Sulfamates Thiazoles Ketoxime ethers