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 bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

used primarily to treat infections caused by

gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

such as ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. a ...

''. This may include

bone infections Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...

endometritis Endometritis is inflammation of the inner lining of the uterus (endometrium). Symptoms may include fever, lower abdominal pain, and abnormal vaginal bleeding or discharge. It is the most common cause of infection after childbirth. It is also pa ...

, intra abdominal infections,

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...

urinary tract infections A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...

, and

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

. 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 nutrie ...

intramuscular Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles ha ...

injection or by

inhalation Inhalation (or Inspiration) happens when air or other gases enter the lungs. Inhalation of air Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...

. Common side effects when given by injection include pain at the site of injection, vomiting, and rash. Common side effects when inhaled include

wheezing A wheeze is a continuous, coarse, whistling sound produced in the respiratory airways during breathing. For wheezes to occur, some part of the respiratory tree must be narrowed or obstructed (for example narrowing of the lower respiratory tract ...

, cough, and vomiting. Serious side effects include ''Clostridium difficile'' infection and

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

including

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

. Those who are allergic to other

β-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...

have a low rate of allergy to aztreonam. Use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

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

cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mec ...

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 peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...

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 The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

in 2019. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

. It is a manufactured version of a chemical from the bacterium ''

Chromobacterium violaceum ''Chromobacterium violaceum'' is a Gram-negative, facultative anaerobic, non-sporing coccobacillus. It is motile with the help of a single flagellum which is located at the pole of the coccobacillus. Usually, there are one or two more lateral ...

''.

Medical uses

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

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Ot ...

and are approved for such use in Europe and the US; they are also used off-label for

non-CF bronchiectasis Bronchiectasis is a disease in which there is permanent enlargement of parts of the bronchi, airways of the lung. Symptoms typically include a chronic cough with sputum, mucus production. Other symptoms include shortness of breath, hemoptysis, co ...

ventilator-associated pneumonia Ventilator-associated pneumonia (VAP) is a type of lung infection that occurs in people who are on mechanical ventilation breathing machines in hospitals. As such, VAP typically affects critically ill persons that are in an intensive care unit ( ...

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

, mycobacterial disease, and to treat infections in people who have received lung transplants. Aztreonam has strong activity against susceptible

Gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

, including ''

''. It is resistant to some

beta-lactamase Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbap ...

s, 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 ''Citrobacter'' is a genus of Gram-negative coliform bacteria in the family Enterobacteriaceae. The species ''C. amalonaticus'', ''C. koseri'', and ''C. freundii'' can use citrate as a sole carbon source. ''Citrobacter'' species are different ...

'', ''

Enterobacter ''Enterobacter'' is a genus of common Gram-negative, facultatively anaerobic, rod-shaped, non-spore-forming bacteria of the family Enterobacteriaceae. It is the type genus of the order Enterobacterales. Several strains of these bacteria are ...

'', '' E. coli'', ''

Haemophilus ''Haemophilus'' is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the family Pasteurellaceae. While ''Haemophilus'' bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of ...

'', ''

Klebsiella ''Klebsiella'' is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. ''Klebsiella'' species are found everywhere in nature. This is thought to be due to distinct sublineages devel ...

'', ''

Proteus In Greek mythology, Proteus (; Ancient Greek: Πρωτεύς, ''Prōteus'') is an early prophetic sea-god or god of rivers and oceanic bodies of water, one of several deities whom Homer calls the "Old Man of the Sea" ''(hálios gérôn)''. ...

'', and ''

Serratia ''Serratia'' is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Yersiniaceae. According to the List of Prokaryotic names with Standing Nomenclature (LPSN), there are currently 19 species of ''Serratia'' that a ...

'' species. The following represents

minimum inhibitory concentration In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria. MIC depends on the microorganism, the affected human being (in vivo only ...

(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 ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'', ''

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

staphylococci ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical ( cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultati ...

, ''

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 posit ...

'', ''Staphylococcus haemolyticus'' and '' Xanthomonas maltophilia'' are resistant to it. Furthermore, ''

Aeromonas hydrophila ''Aeromonas hydrophila'' is a heterotrophic, Gram-negative, rod-shaped bacterium mainly found in areas with a warm climate. This bacterium can be found in fresh or brackish water. It can survive in aerobic and anaerobic environments, and can d ...

'', ''

Citrobacter koseri ''Citrobacter koseri'' is a Gram-negative, non-spore-forming bacillus. It is a facultative anaerobe capable of aerobic respiration. It is motile via peritrichous flagella. It is a member of the family of Enterobacteriaceae. The members of t ...

'' (''Citrobacter diversus''), ''

Pantoea agglomerans ''Pantoea agglomerans'' is a Gram-negative bacterium that belongs to the family Erwiniaceae. It was formerly called ''Enterobacter agglomerans'', or ''Erwinia herbicola'' and is a ubiquitous bacterium commonly isolated from plant surfaces, see ...

'' (''Enterobacter agglomerans''), ''

'' spp. and ''

Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

'' have developed resistance to aztreonam to varying degrees. Aztreonam can be safely used in patients with a penicillin or cephalosporin allergy (except for patients with a

ceftazidime Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, ...

allergy as ceftazidime and aztreonam share a similar side chain). It is also frequently used as an alternative to

aminoglycosides Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside ( sugar). The term can also re ...

because is not ototoxic or nephrotoxic. Aztreonam use has been recently reconsidered for human infections sustained by metallo-beta-lactamase (MBL)-producing Gram-negative bacteria. In these circumstances aztreonam is combined with

avibactam Avibactam is a non-β-lactam β-lactamase inhibitor developed by Actavis (now Teva) jointly with AstraZeneca. A new drug application for avibactam in combination with ceftazidime (branded as Avycaz) was approved by the FDA on February 25, 2015 ...

( ceftazidime/avibactam). 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.

Administration

Aztreonam is poorly absorbed when given orally, so it must be administered as an

injection (trade name Azactam), or inhaled (trade 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 federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) approved the inhalation form on 22 February 2010, for the suppression of ''P. aeruginosa'' infections in patients with

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

Side effects

Reported side effects include injection site reactions,

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, c ...

, and rarely

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later ...

. Gastrointestinal side effects generally include

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, 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, gastroenter ...

. There may be drug-induced

eosinophilia Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/ μL). The hypereosinophilic sy ...

. Because of the unfused beta-lactam ring there is somewhat lower cross-reactivity between aztreonam and many other

beta-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible i ...

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 antibiotics ...

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

, 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 β-lactam antibiotics originally obtained from '' Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum usin ...

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

crosslinking. It has a very high affinity for

penicillin-binding protein Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was disc ...

-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. Gram-positive bact ...

and

anaerobic Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to: * Anaerobic adhesive, a bonding a ...

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 antibiotics ...

References

External links

* {{Portal bar, Medicine Bristol Myers Squibb Conjugated ketones Enantiopure drugs Monobactam antibiotics Wikipedia medicine articles ready to translate Sulfamates Thiazoles