Antibiotics

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

  • Pharmacology
  • Antibiotics
  • 2020-08-04 00:13:54
  • 8 minutes, 47 seconds

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

1 to 2 g IV every 8 or 12 hours

For severe or life-threatening infections, a dose of 2 g IV every 6 to 8 hours is recommended. Therapy should be continued for approximately 10 to 14 days, depending on the nature and severity of the infection.

Usual Adult Dose for Osteomyelitis

1 to 2 g IV every 8 or 12 hours

For severe or life-threatening infections, a dose of 2 g IV every 6 to 8 hours is recommended. Therapy should be continued for approximately 4 to 6 weeks, depending on the nature and severity of the infection. Chronic osteomyelitis may require an additional 2 months of oral antibiotics.

Usual Adult Dose for Pelvic Inflammatory Disease

1 to 2 g IV every 8 or 12 hours

For severe or life-threatening infections, a dose of 2 g IV every 6 to 8 hours is recommended. Therapy should be continued until this patient is afebrile and pain-free for 24 to 36 hours.

Usual Adult Dose for Pneumonia

1 to 2 g IV every 8 or 12 hours

For severe or life-threatening infections, a dose of 2 g IV every 6 to 8 hours is recommended. Therapy should be continued for approximately 21 days, depending on the nature and severity of the infection.

Usual Adult Dose for Pyelonephritis

1 to 2 g IV every 8 or 12 hours

For severe or life-threatening infections, a dose of 2 g IV every 6 to 8 hours is recommended. Therapy should be continued for approximately 14 days, depending on the nature and severity of the infection.

Usual Adult Dose for Skin or Soft Tissue Infection

1 to 2 g IV every 8 or 12 hours

For severe or life-threatening infections, a dose of 2 g IV every 6 to 8 hours is recommended. Therapy should be continued for approximately 7 days or until 3 days after acute inflammation disappears. For more severe infections, such as diabetic soft tissue infections, 14 to 21 days of therapy may be required.

Usual Adult Dose for Urinary Tract Infection

500 mg to 1 g IV or IM every 8 to 12 hours

Usual Pediatric Dose for Urinary Tract Infection, skin and structure infection, cystic fibrosis, bacterial infection, pneumonia, intraabdominal infection

7 days or less, 2000 g or less: 30 mg/kg IV every 12 hours

7 days or less, 2001 g or more: 30 mg/kg IV every 8 hours

8 to 30 days, 1199 g or less: 30 mg/kg IV every 12 hours

8 to 30 days, 1200 to 2000 g: 30 mg/kg IV every 8 hours

8 to 30 days, 2001 g or more: 30 mg/kg IV every 6 hours

1 month to 18 years: 30 mg/kg IV every 6 to 8 hours, up to a maximum of 2 g/dose or 8 g/day

Usual Pediatric Dose for Cystic Fibrosis

Inhalation:

7 years or older:

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.

Renal Dose Adjustments

Parenteral:

CrCl 10 to 30 mL/min: a Loading dose of 1 to 2 g IV followed by one-half of the normal dose at the usual dosage interval

CrCl 9 mL/min or less: a Loading dose of 500 mg to 2 g IV followed by one-fourth of the normal dose at the usual dosage interval

Inhalation: No adjustment recommended.

Liver Dose Adjustments

No adjustment recommended.

Dose Adjustments

Because of the serious nature of infections due to Pseudomonas Aeruginosa, a dosage of 2 g IV every 6 to 8 hours is recommended, at least upon initiation of therapy, in systemic infections caused by this organism.

Precautions in the use of aztreonam

Serious and occasionally fatal hypersensitivity reactions have been reported with antibiotics. The drug should be discontinued immediately at the first appearance of skin rash or other signs of hypersensitivity and treatment should be initiated as appropriate.

Severe, acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures including oxygen, intravenous fluids, antihistamines, corticosteroids, cardiovascular support, and airway management as clinically indicated.

Clostridium difficile associated diarrhea (CDAD) has been reported with almost all antibiotics and may potentially be life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea following aztreonam therapy.

Mild cases generally improve with discontinuation of the drug, while severe cases may require supportive therapy and treatment with an antimicrobial agent effective against C difficile. Hypertoxin producing strains of C difficile cause increased morbidity and mortality; these infections can be resistant to antimicrobial treatment and may necessitate colectomy.

Patients with renal or hepatic impairment should be monitored during therapy. Renal, hepatic, and hematopoietic monitoring is recommended periodically during prolonged therapy.

Renal function should be monitored, especially in elderly patients.

Safety and effectiveness of aztreonam for inhalation have not been established in patients with forced expiratory volume in 1 second (FEV1) less than 25% or greater than 75% predicted or in patients colonized with Burkholderia cepacia.

Safety and effectiveness of aztreonam for inhalation have not been established in pediatric patients less than 7 years of age.

Dialysis

Parenteral: For serious or life-threatening infections, in addition to the maintenance doses, one-eighth of the initial dose should be given after each hemodialysis.

Inhalation: No adjustment recommended.

Other Comments

The maximum recommended parenteral dose is 8 g/day.

If necessary, doses of 1 g or less may be given intramuscularly in moderately severe infections; however, IM administration may be a problem for patients with an end-stage renal disease if there is an underlying coagulopathy.

The IV route is recommended for patients requiring single doses greater than 1 g or those with bacterial septicemia, localized parenchymal abscess (e.g., intraabdominal abscess), peritonitis, or other severe systemic or life-threatening infections.

Generally, aztreonam should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Persistent infections may require treatment for several weeks.

Following reconstitution, aztreonam for inhalation should be used at once using the Altera (R) Nebulizer System. It should not be used with any other nebulizer. Aztreonam for inhalation should not be mixed with any other drug in the Altera (R) Nebulizer Handset.

The use of a bronchodilator prior to administration of aztreonam for inhalation is recommended. Short-acting bronchodilators can be taken between 15 minutes and 4 hours prior to each dose and long-acting bronchodilators can be taken between 30 minutes and 12 hours prior to administration of aztreonam for inhalation.

The drug is available in strengths of: 1 g/50 mL; 2 g/50 mL; 500 mg; 1 g; 2 g; 75 mg


References:
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Daniel Ogera

Medical educator, passionate about simplifying difficult medical concepts for easier understanding and mastery by nursing and medical students.

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About this article:
  • Topic:Pharmacology
  • Duration:8 minutes, 47 seconds
  • Subtopic:Antibiotics

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