What is the recommended dose of Azetreonam (Aztreonam) for patients with normal or impaired renal function?

Azetreonam Dosing Recommendations for Normal and Impaired Renal Function

For patients with normal renal function, azetreonam should be dosed at 1-2g every 8-12 hours for moderate infections and 2g every 6-8 hours for severe systemic or life-threatening infections, with dosage adjustments required for patients with renal impairment. 1

Adult Dosing Guidelines

Normal Renal Function

• For urinary tract infections: 500mg or 1g every 8-12 hours 1
• For moderately severe systemic infections: 1g or 2g every 8-12 hours 1
• For severe systemic or life-threatening infections: 2g every 6-8 hours 1
• For Pseudomonas aeruginosa infections: 2g every 6-8 hours is recommended at least upon initiation of therapy 1

Impaired Renal Function

• For patients with creatinine clearance between 10-30 mL/min/1.73m²: Administer an initial loading dose of 1g or 2g, then reduce maintenance dose by 50% at the usual fixed interval 1, 2
• For patients with severe renal failure (creatinine clearance <10 mL/min/1.73m²): Administer the usual initial dose (500mg, 1g, or 2g), then reduce maintenance dose to one-fourth of the usual initial dose at the usual fixed interval 1
• For hemodialysis patients: In addition to maintenance doses, administer one-eighth of the initial dose after each hemodialysis session for serious or life-threatening infections 1

Pediatric Dosing Guidelines

• For mild to moderate infections: 30 mg/kg every 8 hours 3
• For moderate to severe infections: 30 mg/kg every 6-8 hours 3
• Maximum recommended dose: 120 mg/kg/day 3

Route of Administration

• Intravenous route is recommended for:
  • Patients requiring single doses greater than 1g 1
  • Patients with bacterial septicemia 1
  • Patients with localized parenchymal abscess (e.g., intra-abdominal abscess) 1
  • Patients with peritonitis 1
  • Patients with other severe systemic or life-threatening infections 1
• Intramuscular administration is suitable for less severe infections 1, 4

Pharmacokinetic Considerations

• Serum half-life in patients with normal renal function: 1.5-2.1 hours 4
• Primary route of elimination: Urine (60-70% excreted unchanged) 5
• Serum clearance is directly proportional to creatinine clearance 5, 2
• For elderly patients, renal status is a major determinant of dosage 1, 6
• Creatinine clearance estimation formula when only serum creatinine is available:
  • Males: Clcr = [weight (kg) × (140−age)] / [72 × serum creatinine (mg/dL)]
  • Females: Clcr = 0.85 × above value 1

Clinical Applications

• Aztreonam is effective against aerobic gram-negative bacteria, including Pseudomonas aeruginosa, but lacks activity against gram-positive and anaerobic bacteria 4, 5
• For mixed infections involving gram-positive or anaerobic organisms, concurrent therapy with appropriate antibiotics is recommended 4, 7
• Aztreonam is a good alternative to aminoglycosides in elderly patients with impaired renal function due to its lower nephrotoxicity profile 6
• Population pharmacokinetic modeling supports adequate probability of target attainment (>90%) with the recommended dose adjustments for patients with moderate and severe renal impairment 2

Important Considerations

• Duration of therapy depends on infection severity; generally, continue for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained 1
• Persistent infections may require treatment for several weeks 1
• Aztreonam has been shown to be effective and safe in treating serious gram-negative infections even in elderly patients with impaired renal function 6
• For optimal pharmacodynamic effect, dosing should be optimized based on pharmacokinetic/pharmacodynamic principles 3