Drugs List

Therapeutic Indications

Uses

Treatment of infections caused by susceptible aerobic Gram-negative micro-organisms. Type of infection include:

Urinary tract infections: including pyelonephritis, cystitis (initial and recurrent), asymptomatic bacteriuria (including infection resistant to aminoglycosides, cephalosporins or penicillins)

Gonorrhoea: acute uncomplicated urogenital or anorectal infection due to Neisseria gonorrhoeae (beta-lactamase producing or non-producing strains)

Lower respiratory tract infections: including pneumonia, bronchitis, lung infections in patients with cystic fibrosis

Bacteraemia/septicaemia

Meningitis caused by Haemophilus influenzae or Neisseria meningitidis: aztreonam is active against Gram-negative micro-organisms, therefore for initial blind therapy an antibiotic active against Gram-positive micro-organisms may be administered concurrently before results of sensitivity tests are known.

Bone and joint infections

Skin and soft tissue infections: including infections in post-operative wounds, ulcers and burns.

Intra-abdominal infections: peritonitis

Gynaecological infections: pelvic inflammatory disease, endometritis and pelvic cellulitis

Aztreonam may be used as an adjunctive therapy to surgery in the management of infections caused by susceptible organisms. These include abscesses, infections complicating hollow viscus perforations, cutaneous infections and infections of serous surfaces.

Bacteriological studies to determine the pathogen and their sensitivity to aztreonam should be performed, although therapy may be started before the results are known.
Additional Gram-positive therapy should be administered concurrently to provide broad-spectrum coverage until the results of bacteriological studies are returned. Once the result are known the appropriate antibiotic should be continued.
Patients with serious Pseudomonas infections may benefit from concurrent aminoglycoside administration. Clinical data relating to aminoglycosides should be considered when this combination is used.

Administration

Aztreonam may be administered by intramuscular injection or intravenous injection/infusion.

The intravenous route is recommended with single doses greater than 1g, and in patients with bacterial septicaemia, localised parenchymal abscess (e.g. intra-abdominal abscess), peritonitis, meningitis or other severe systemic or life threatening infections.

Intramuscular injection
Administer by deep intramuscular injection into a large muscle mass, such as the upper quadrant of the gluteus maximus or the lateral part of the thigh.

Intravenous injection
Administer over a period of 3-5 minutes.

Intravenous infusion
Administer over 20-60 minutes.

Reconstitution

When the diluent is added to the powder, the solution should be shaken immediately and vigorously.
Reconstituted solutions are for single use only and any unused solution should be discarded.
The pH of the reconstituted solution ranges from 4.5 to 7.5 and the colour may vary from colourless to light yellow, which may develop a pink tint on standing.

Intramuscular injection
To the 500mg vial add 1.5ml of water for injections or 0.9% sodium chloride injection and shake well.
To the 1g vial add 3ml of water for injections or 0.9% sodium chloride injection and shake well.

Intravenous injection
Add 6-10ml of water for injections to the vial and shake well.

Intravenous infusion
For each gram of aztreonam add at least 3ml water for injections and shake well.
Dilute this further with an appropriate infusion solution (see Compatibilities) to a final concentration less than 2% w/v (at least 50ml solution per gram of aztreonam).
A volume control administration set may be used to deliver the initial aztreonam solution into the infusion solution.

Compatibilities

For intravenous infusion, the reconstituted solution may be diluted with:

0.9% sodium chloride injection
5% glucose intravenous infusion
5% or 10% mannitol intravenous infusion
Sodium lactate intravenous infusion
0.9% sodium chloride and 5% glucose intravenous infusion
0.45% sodium chloride and 5% glucose intravenous infusion
0.2% sodium chloride and 5% glucose intravenous infusion
Compound sodium chloride injection (Ringers solution for injection)
Compound sodium lactate intravenous infusion (Hartmann's solution for injection)

Incompatibilities

Aztreonam should not be physically mixed with any other drug, antibiotic or diluent (except those listed in Compatibilities section ).

With intermittent infusion of aztreonam and another drug via a common delivery tube, the tube should be flushed before and after delivery of aztreonam with any appropriate infusion solution compatible with both drug solutions. The drugs should not be delivered simultaneously.

Contraindications

Pregnancy - see Pregnancy section

Precautions and Warnings

Cross-reactivity between aztreonam and antibodies to penicillin or cephalosporins has not been established. Patients with a history of hypersensitivity to beta-lactams should therefore be treated with caution until further evidence is gained.

Additional Gram-positive therapy should be administered concurrently to provide broad-spectrum coverage until the results of bacteriological studies are returned. Once the result are known the appropriate antibiotic should be continued.

Clostridium difficile associated diarrhoea (CDAD) has been reported in patients using antibacterial agents, this may range from mild diarrhoea to fatal colitis. If CDAD is confirmed or suspected, antibiotic use not directed at C. difficile may need to be discontinued.

Use with caution and monitor hepatic function in patients with hepatic impairment. A dose reduction is suggested for long-term treatment of patients with chronic liver disease with cirrhosis - see Dosage; Hepatic Impairment.

Maintenance doses should be reduced in patients with creatinine clearance less than 30ml/minute - see Dosage; Renal Impairment.

Long term bacterial eradication may not be achieved in patients experiencing acute pulmonary exacerbations of cystic fibrosis. Clinical improvement should be evident with therapy.

Overgrowth of non-susceptible organisms (including Gram-positive organisms and fungi) may occur with aztreonam therapy. Additional antimicrobial therapy may consequently be required.

Positive direct or indirect Coombs test may develop during treatment with aztreonam.

Treatment with aztreonam should be stopped if patients develop serious blood or skin disorders ( e.g. pancytopenia or toxic epiderma necrolysis).

Breastfeeding - see Lactation section.

Use with caution in neonates under 7 days. See Dosage; Neonates.

Pregnancy and Lactation

Pregnancy

The manufacturer contraindicate the use of aztreonam during pregnancy.

Aztreonam crosses the placenta and enters the foetal circulation.

Animal studies have shown no evidence of embryotoxicity, foetotoxicity or teratogenicity with doses up to 15 times the maximum recommended human dose.

Schaefer concludes that aztreonam can be used during pregnancy when strongly indicated, such as in cases where penicillins or cephalosporins have been ineffective.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

The manufacturer advises that lactating mothers should refrain from breastfeeding during the course of therapy.

Aztreonam is excreted into breast milk in low levels. However, due to poor oral absorption (less than 1%) no untoward effects would be expected in the nursing infant, except from changes in the gastrointestinal flora.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Rash
Pruritus
Urticaria
Erythema multiforme
Petechiae
Exfoliative dermatitis
Flushing
Toxic epidermal necrolysis
Eosinophilia
Prothrombin time increased
Increased partial thromboplastin time
Thrombocytopenia
Neutropenia
Anaemia
Pancytopenia
Jaundice
Hepatitis
Increase of liver transaminases
Increase in alkaline phosphatase
Hypersensitivity reactions
Anaphylactic reaction
Angioedema
Bronchospasm
Diarrhoea
Pseudomembranous colitis
Antibiotic-associated colitis
Gastrointestinal bleeding
Nausea
Vomiting
Abdominal cramps
Mouth ulcers
Taste disturbances
Phlebitis
Injection site reactions
Vaginitis
Candidiasis
Seizures
Dyspnoea
Hypotension
Asthenia
Confusion
Dizziness
Vertigo
Sweating
Headache
Breast tenderness
Halitosis
Muscle ache
Fever
Malaise
Sneezing
Nasal congestion
Serum creatinine increased
Thrombocythaemia
Leukocytosis
Positive Coombs test
Insomnia
Paraesthesia
Dysgeusia
Diplopia
Tinnitus
Haemorrhage
Thrombophlebitis
Chest pain
Pyrexia
ECG changes
Wheezing
Purpura
Weakness

Presentation

Powder for solution for injection or infusion containing 1g aztreonam per vial
Powder for solution for injection or infusion containing 2g aztreonam per vial

Drugs List

Therapeutic Indications

Uses

Treatment of infections caused by susceptible aerobic Gram-negative micro-organisms. Type of infection include:

Urinary tract infections: including pyelonephritis, cystitis (initial and recurrent), asymptomatic bacteriuria (including infection resistant to aminoglycosides, cephalosporins or penicillins)

Gonorrhoea: acute uncomplicated urogenital or anorectal infection due to Neisseria gonorrhoeae (beta-lactamase producing or non-producing strains)

Lower respiratory tract infections: including pneumonia, bronchitis, lung infections in patients with cystic fibrosis

Bacteraemia/septicaemia

Meningitis caused by Haemophilus influenzae or Neisseria meningitidis: aztreonam is active against Gram-negative micro-organisms, therefore for initial blind therapy an antibiotic active against Gram-positive micro-organisms may be administered concurrently before results of sensitivity tests are known.

Bone and joint infections

Skin and soft tissue infections: including infections in post-operative wounds, ulcers and burns.

Intra-abdominal infections: peritonitis

Gynaecological infections: pelvic inflammatory disease, endometritis and pelvic cellulitis

Aztreonam may be used as an adjunctive therapy to surgery in the management of infections caused by susceptible organisms. These include abscesses, infections complicating hollow viscus perforations, cutaneous infections and infections of serous surfaces.

Bacteriological studies to determine the pathogen and their sensitivity to aztreonam should be performed, although therapy may be started before the results are known.
Additional Gram-positive therapy should be administered concurrently to provide broad-spectrum coverage until the results of bacteriological studies are returned. Once the result are known the appropriate antibiotic should be continued.
Patients with serious Pseudomonas infections may benefit from concurrent aminoglycoside administration. Clinical data relating to aminoglycosides should be considered when this combination is used.

Dosage

The dose and route of administration should be determined by the susceptibility of the pathogen, the severity of the infection and the condition of the patient.

Adults

Children

Neonates

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

Aztreonam may be administered by intramuscular injection or intravenous injection/infusion.

The intravenous route is recommended with single doses greater than 1g, and in patients with bacterial septicaemia, localised parenchymal abscess (e.g. intra-abdominal abscess), peritonitis, meningitis or other severe systemic or life threatening infections.

Intramuscular injection
Administer by deep intramuscular injection into a large muscle mass, such as the upper quadrant of the gluteus maximus or the lateral part of the thigh.

Intravenous injection
Administer over a period of 3-5 minutes.

Intravenous infusion
Administer over 20-60 minutes.

Reconstitution

When the diluent is added to the powder, the solution should be shaken immediately and vigorously.
Reconstituted solutions are for single use only and any unused solution should be discarded.
The pH of the reconstituted solution ranges from 4.5 to 7.5 and the colour may vary from colourless to light yellow, which may develop a pink tint on standing.

Intramuscular injection
To the 500mg vial add 1.5ml of water for injections or 0.9% sodium chloride injection and shake well.
To the 1g vial add 3ml of water for injections or 0.9% sodium chloride injection and shake well.

Intravenous injection
Add 6-10ml of water for injections to the vial and shake well.

Intravenous infusion
For each gram of aztreonam add at least 3ml water for injections and shake well.
Dilute this further with an appropriate infusion solution (see Compatibilities) to a final concentration less than 2% w/v (at least 50ml solution per gram of aztreonam).
A volume control administration set may be used to deliver the initial aztreonam solution into the infusion solution.

Compatibilities

For intravenous infusion, the reconstituted solution may be diluted with:

0.9% sodium chloride injection
5% glucose intravenous infusion
5% or 10% mannitol intravenous infusion
Sodium lactate intravenous infusion
0.9% sodium chloride and 5% glucose intravenous infusion
0.45% sodium chloride and 5% glucose intravenous infusion
0.2% sodium chloride and 5% glucose intravenous infusion
Compound sodium chloride injection (Ringers solution for injection)
Compound sodium lactate intravenous infusion (Hartmann's solution for injection)

Incompatibilities

Aztreonam should not be physically mixed with any other drug, antibiotic or diluent (except those listed in Compatibilities section ).

With intermittent infusion of aztreonam and another drug via a common delivery tube, the tube should be flushed before and after delivery of aztreonam with any appropriate infusion solution compatible with both drug solutions. The drugs should not be delivered simultaneously.

Contraindications

Pregnancy - see Pregnancy section

Precautions and Warnings

Cross-reactivity between aztreonam and antibodies to penicillin or cephalosporins has not been established. Patients with a history of hypersensitivity to beta-lactams should therefore be treated with caution until further evidence is gained.

Additional Gram-positive therapy should be administered concurrently to provide broad-spectrum coverage until the results of bacteriological studies are returned. Once the result are known the appropriate antibiotic should be continued.

Clostridium difficile associated diarrhoea (CDAD) has been reported in patients using antibacterial agents, this may range from mild diarrhoea to fatal colitis. If CDAD is confirmed or suspected, antibiotic use not directed at C. difficile may need to be discontinued.

Use with caution and monitor hepatic function in patients with hepatic impairment. A dose reduction is suggested for long-term treatment of patients with chronic liver disease with cirrhosis - see Dosage; Hepatic Impairment.

Maintenance doses should be reduced in patients with creatinine clearance less than 30ml/minute - see Dosage; Renal Impairment.

Long term bacterial eradication may not be achieved in patients experiencing acute pulmonary exacerbations of cystic fibrosis. Clinical improvement should be evident with therapy.

Overgrowth of non-susceptible organisms (including Gram-positive organisms and fungi) may occur with aztreonam therapy. Additional antimicrobial therapy may consequently be required.

Positive direct or indirect Coombs test may develop during treatment with aztreonam.

Treatment with aztreonam should be stopped if patients develop serious blood or skin disorders ( e.g. pancytopenia or toxic epiderma necrolysis).

Breastfeeding - see Lactation section.

Use with caution in neonates under 7 days. See Dosage; Neonates.

Pregnancy and Lactation

Pregnancy

The manufacturer contraindicate the use of aztreonam during pregnancy.

Aztreonam crosses the placenta and enters the foetal circulation.

Animal studies have shown no evidence of embryotoxicity, foetotoxicity or teratogenicity with doses up to 15 times the maximum recommended human dose.

Schaefer concludes that aztreonam can be used during pregnancy when strongly indicated, such as in cases where penicillins or cephalosporins have been ineffective.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

The manufacturer advises that lactating mothers should refrain from breastfeeding during the course of therapy.

Aztreonam is excreted into breast milk in low levels. However, due to poor oral absorption (less than 1%) no untoward effects would be expected in the nursing infant, except from changes in the gastrointestinal flora.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

No studies on the effects on the ability to drive or operate machines have been performed.

Side Effects

Rash
Pruritus
Urticaria
Erythema multiforme
Petechiae
Exfoliative dermatitis
Flushing
Toxic epidermal necrolysis
Eosinophilia
Prothrombin time increased
Increased partial thromboplastin time
Thrombocytopenia
Neutropenia
Anaemia
Pancytopenia
Jaundice
Hepatitis
Increase of liver transaminases
Increase in alkaline phosphatase
Hypersensitivity reactions
Anaphylactic reaction
Angioedema
Bronchospasm
Diarrhoea
Pseudomembranous colitis
Antibiotic-associated colitis
Gastrointestinal bleeding
Nausea
Vomiting
Abdominal cramps
Mouth ulcers
Taste disturbances
Phlebitis
Injection site reactions
Vaginitis
Candidiasis
Seizures
Dyspnoea
Hypotension
Asthenia
Confusion
Dizziness
Vertigo
Sweating
Headache
Breast tenderness
Halitosis
Muscle ache
Fever
Malaise
Sneezing
Nasal congestion
Serum creatinine increased
Thrombocythaemia
Leukocytosis
Positive Coombs test
Insomnia
Paraesthesia
Dysgeusia
Diplopia
Tinnitus
Haemorrhage
Thrombophlebitis
Chest pain
Pyrexia
ECG changes
Wheezing
Purpura
Weakness

Effects on Laboratory Tests

Positive direct or indirect Coombs test may develop during treatment with aztreonam.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Before reconstitution
Do not store above 25 degrees C.

After reconstitution
Store at 2-8 degrees C for no longer than 24 hours.
Any unused solution should be discarded.

Further Information

Last Full Review Date: August 2011

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Azactam 1g or 2g Powder for Solution for Injection or Infusion. E.R Squibb & Sons Ltd. Revised April 2014.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 17 August 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Aztreonam. Last revised: November 1, 2010
Last accessed: July 21, 2011