Aztreonam is among the first antibiotics of the new class, the monobactams. It is primarily used to treat infections caused by gram-negative bacteria especially for the treatment of pseudomonas aeruginosa.

It is used to treat patients with infections caused by gram-negative organisms of the following organs:

• Urinary tract infections

• Lower respiratory tract infections

• Septicemia

• Skin and soft tissue infections

• Intra-abdominal infections

• Gynecological infections

Other Off-Label uses of Aztreonam in Adults include:

• Bacterial meningitis

• Native vertebral osteomyelitis

• Perioperative surgical prophylaxis

Aztreonam Dose in Adults

Dose in the treatment of Urinary tract infection:

• 500 mg to 1 gm twice or thrice daily to a maximum of 8 gms/day

Moderately severe systemic infections:

• 2 gms intravenous two or three times a day to a  maximum dose of 8 gms/day.
• The intravenous route is the preferred route for severe infections like septicemia, peritonitis, and intra-abdominal infections.
• Patients with cystic fibrosis require a higher dose

Severe systemic or life-threatening infections especially caused by Pseudomonas aeruginosa:

• 2 gms intravenous three or four times a day to a maximum dose of 8 gms//day.
• Patients with cystic fibrosis may require higher doses.

Dose as an alternative agent in the treatment of community-acquired or health-care-associated bacterial meningitis (off label):

• As a pathogen-specific treatment or as an empirical treatment for healthcare-associated infections (eg, beta-lactamase positive Haemophilus influenzae, Enterobacteriaceae or Pseudomonas aeruginosa):
  • 2 gms intravenously administered three or four times a day, along with other suitable drugs

Dose in the treatment of native vertebral osteomyelitis due to P. aeruginosa as off-label use:

• 2 gms intravenous thrice a day for 6 weeks.
• Use in combination with other antipseudomonal drugs such as aminoglycosides

Dose in the treatment of hospital-acquired or ventilator-associated pneumonia as an alternative therapy:

• 2 gms intravenously every 8 hours for 7 days.

Perioperative dose in surgical prophylaxis as off-label use:

• 2 gms intravenously one hour prior to surgery.
• Doses may be repeated in 4 hours if the procedure is lengthy or if there is excessive blood loss.

Aztreonam Dose in Children

General dosing of aztreonam in susceptible infection:

• Mild to moderate infection:
  • 90 mg/kg/day intramuscular in divided doses every 8 hours to a maximum daily dose of 3,000 mg/day.
• Severe infection:
  • 90 - 120 mg/kg/day in divided doses every 6 - 8 hours to a maximum daily dose of 8 gms/day.

Dose in the treatment of Cystic fibrosis (Pseudomonas aeruginosa):

• 150 - 200 mg/kg/day intravenously in divided doses every 6 - 8 hours to a maximum daily dose of 12 gms/day.

Dose in the treatment of complicated intra-abdominal infections:

• 90 - 120 mg/kg/day intravenous 3 - 4 times a day in combination with metronidazole to a maximum dose of 2,000 mg.

Dose in the treatment of Peritonitis:

• A loading dose of 1,000 mg per liter of dialysate intraperitoneal.
• A maintenance dose of 250 mg per liter.

Dose in the Surgical prophylaxis:

• 30 mg/kg intravenously one hour prior to the procedure.
• The dose may be repeated in 4 hours if there is excessive blood loss and in prolonged procedures.

Pregnancy Risk Factor B

• Aztreonam crosses the placental barrier but adverse fetal events have not been observed.

Aztreonam use during breastfeeding:

• Less than 1% of the drug is excreted into breastmilk.
• The manufacturer recommends to temporarily discontinue the drug during nursing.

Aztreonam Dose in Renal Disease:

• CrCl 10 - 30 mL/minute:

  • Administer 50% of the usual dose.

• CrCl of less than 10 mL/minute:

  • Administer 25% of the usual dosage.

• Intermittent hemodialysis:

  • 20 - 50% of the drug is dialyzable:
    • A loading dose of 500 mg, 1 gm, or 2 gms, followed by 25% of the initial dose at the usual interval
    • Patients with serious infections should be given an additional 12.5% of the dose after each hemodialysis in addition to the usual maintenance dose.
  • Alternatively, the patient may be administered 500 mg twice a day.

• Peritoneal dialysis:

  • Administer the dose as for CrCl of less than 10 mL/minute.

• Continuous renal replacement therapy:

  • CVVH: A loading dose of 2 gms followed by 1 - 2 gms twice a day.
  • CVVHD/CVVHDF: A loading dose of 2 gms followed by either 1 gm thrice daily or 2 gms twice a day.

Aztreonam Dose in Liver Disease:

Dose adjustment in patients with liver disease is not recommended.

Common Side Effects of Aztreonam Include:

• Hematologic & oncologic:
  • Neutropenia
• Hepatic:
  • Increased serum transaminases
• Local:
  • Pain at the injection site

Less Common Side Effects of Aztreonam Include:

• Cardiovascular:
  • Phlebitis
  • Thrombophlebitis
• Dermatologic:
  • Skin rash
• Gastrointestinal:
  • Diarrhea
  • Nausea
  • Vomiting
• Hematologic & oncologic:
  • Eosinophilia
  • Thrombocythemia
• Local:
  • Erythema, discomfort, and swelling at the injection site.
• Renal:
  • Increased serum creatinine
• Miscellaneous:
  • Fever

Contraindication to Aztreonam Include:

Allergy reactions to aztreonam and any component of the formulation

Warnings and Precautions

• Beta-lactam allergy:
  • Patients who have previously experienced allergic responses to beta-lactams shouldn't use it.
  • Rare cross-allergenicity to cephalosporins, penicillins, and carbapenems can occur.
• Superinfection
  • Cefepime-treated patients for more than two months may contract superinfections, including fungal or bacterial superinfections. 
  • C. difficile-associated diarrhea, (CDAD), and pseudomembranous collitis can occur.
• Renal impairment
  • Warnings and dosage adjustments should be given to patients with compromised renal function.

Aztreonam (systemic): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters :

Monitor renal and liver function tests periodically. The patient should also be monitored for clinical features of anaphylaxis. 

How to Administer Aztreonam?

• It can be administered as an intramuscular or intravenous injection.
• Doses greater than 1  gms should be administered intravenously.

Intramuscular administration:

• Administer the drug into a large muscle by deep injection such as the lateral part of the thigh or the upper outer quadrant of gluteus maximus.

Intravenous administration:

• Administer intravenously as a slow push over 3 - 5 minutes or by intermittent infusion over 20 - 60 minutes.

Mechanism of action of Aztreonam:

• It inhibits cell wall formation by binding to penicillin-binding proteins.
• As a result, the last stage of peptidoglycan synthesis in bacterial cell wall cells is inhibited.
• Cell wall autolytic enzymes then act on bacteria to cause their lysis.
• Cross-allergenicity is unlikely due to the monobactam structure. Aztreonam is a monobactam antibiotic.

Other antibiotics of the same class include:

• Tigemonam
• Nocardicin A
• Tabtoxin

It is well absorbed after intramuscular injections with plasma levels comparable to the intravenous administration.

It is extensively incorporated into bodily tissues like bone, bile, peritoneal fluid, bronchial secretions, and cerebrospinal fluid.

Distribution into CSF changes in inflammatory states as follows: blood level ratio: Meninges in inflamed states is 8% to 40%: Normal states is 1%.

56% of the drug is protein-bound. It is metabolized by the liver and has a half-life elimination as follows:

• Neonates less than 7 days and ≤2.5 kg: 5.5 to 9.9 hours, Less than 7 days and >2.5 kg: 2.6 hours,  1 week - 1 month: 2.4 hours
• Children 2 months to 12 years: 1.7 hours
• Children with cystic fibrosis: 1.3 hours
• Adults with normal renal function: 1.5 - 2 hours
• End-stage renal disease (ESRD): 6 - 8.4 hours

The time to reach peak plasma concentration after intramuscular injection is within 60 minutes. It is excreted primarily in the urine as unchanged drug (60 - 70%).

International Brands of Aztreonam:

• Atreon
• Azactam
• Azanem
• Azenam
• Azeus
• Aznam
• Azom
• Azonam
• Aztreo
• Aztreobol
• Bencipen
• Finacide
• Mezactam
• Monobac
• Primbactam
• Reonam
• SG-Nam
• Treonam
• Vebac
• Zactaject

Aztreonam injection Brands in Pakistan:

Other antipseudomonal drugs include:

• Cefepime,
• Piperacillin-Tazobactam,
• ceftizidime,
• quinolones,
• aminoglycosides, and
• Carbapenems