What is the recommended dosage for aztreonam (Aztreonam) in patients with normal and impaired renal function?

Aztreonam Dosage Guidelines for Normal and Impaired Renal Function

The recommended dosage of aztreonam for adults with normal renal function ranges from 500 mg to 2 g every 6-12 hours depending on infection severity, with a maximum of 8 g per day. 1

Adult Dosing for Normal Renal Function

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

The intravenous route is preferred for patients requiring single doses greater than 1 g or those with bacterial septicemia, localized parenchymal abscess, peritonitis, or other severe systemic infections 1.

Dosing in Renal Impairment

• For patients with creatinine clearance between 10-30 mL/min/1.73 m²: Dose should be halved after an initial loading dose of 1 g or 2 g 1, 3
• For patients with severe renal failure (creatinine clearance <10 mL/min/1.73 m²): Give the usual initial dose (500 mg, 1 g, or 2 g), followed by maintenance doses of one-fourth the usual initial dose at the standard interval (6,8, or 12 hours) 1, 4
• For hemodialysis patients: In addition to maintenance doses, give one-eighth of the initial dose after each hemodialysis session for serious or life-threatening infections 1

Calculating Creatinine Clearance

When only serum creatinine is available, creatinine clearance can be estimated using the following formula 1:

For males:

Clcr = [weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]

For females:

Clcr = 0.85 × above value

Pediatric Dosing

• For mild to moderate infections: 30 mg/kg every 8 hours 5, 1
• For moderate to severe infections: 30 mg/kg every 6 or 8 hours 1
• Maximum recommended dose: 120 mg/kg/day 5, 1

Elderly Patients

Renal status is a major determinant of dosage in elderly patients who may have diminished renal function. Estimates of creatinine clearance should be obtained and appropriate dosage modifications made if necessary 1, 4.

Administration Considerations

• Aztreonam may be administered intravenously or by intramuscular injection 1, 4
• For patients undergoing hemodialysis, administer after dialysis sessions to avoid premature elimination of the drug 1
• 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

Pharmacokinetic Considerations

• Aztreonam has a serum half-life of 1.7-2.1 hours in patients with normal renal function 6, 4
• After a 2 g IV dose, therapeutic levels exceed MIC90 values for most Enterobacteriaceae for approximately 8 hours 6
• 60-70% of the drug is excreted unchanged in the urine 6, 7
• Population pharmacokinetic modeling supports the FDA-labeled dose adjustments for moderate and severe renal impairment with >90% probability of target attainment 3

Clinical Pearls

• Aztreonam has activity primarily against aerobic gram-negative bacteria including Pseudomonas aeruginosa 2
• For mixed infections or those of unknown etiology, combination therapy is recommended to ensure coverage of gram-positive and anaerobic bacteria 2, 7
• Serum clearance of aztreonam is directly proportional to creatinine clearance, making dosage adjustment essential in renal impairment 6, 3