What is the recommended dosing for aztreonam (Azactam) in adults with normal and impaired renal function?

Aztreonam Dosing for Adults

For adults with normal renal function, aztreonam should be dosed at 1-2 g every 6-8 hours intravenously, with the specific dose and interval determined by infection severity and causative organism. 1

Standard Dosing in Normal Renal Function

The FDA-approved dosing regimen varies by infection type 1:

• Urinary tract infections: 500 mg to 1 g every 8-12 hours
• Moderately severe systemic infections: 1-2 g every 8-12 hours
• Severe systemic or life-threatening infections: 2 g every 6-8 hours
• Maximum daily dose: 8 g per day 1

Special Considerations for Pseudomonas aeruginosa

For infections caused by Pseudomonas aeruginosa, 2 g every 6-8 hours is recommended at least initially, given the serious nature of these infections. 1 This higher dosing is critical because aztreonam serum levels after a 2 g IV dose exceed the MIC90 for P. aeruginosa for only 4-6 hours, compared to 8 hours for most Enterobacteriaceae 1.

Route of Administration

The intravenous route is recommended for 1:

• Single doses greater than 1 g
• Bacterial septicemia
• Localized parenchymal abscess (e.g., intra-abdominal abscess)
• Peritonitis
• Other severe systemic or life-threatening infections

Dosing in Renal Impairment

Aztreonam clearance correlates directly with creatinine clearance, requiring dose adjustment in renal dysfunction. 2, 3

Moderate Renal Impairment (CrCl 10-30 mL/min/1.73 m²)

• Give a full loading dose of 1-2 g initially
• Then reduce maintenance dose to 50% of the usual dose at the standard interval (every 6,8, or 12 hours) 1

For example, if the usual dose is 2 g every 8 hours, give 2 g loading dose, then 1 g every 8 hours.

Severe Renal Impairment (CrCl <10 mL/min/1.73 m²)

• Give the usual initial dose (500 mg, 1 g, or 2 g)
• Maintenance dose should be one-fourth of the usual initial dose at the standard interval 1

For example, if the usual dose is 2 g every 8 hours, give 2 g loading dose, then 500 mg every 8 hours.

Hemodialysis Patients

For serious or life-threatening infections in hemodialysis patients, give one-eighth of the initial dose after each hemodialysis session in addition to the maintenance doses. 1

Estimating Creatinine Clearance

When only serum creatinine is available, use the Cockcroft-Gault equation 1:

• Males: CrCl = [weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]
• Females: 0.85 × male value

The serum creatinine must represent steady-state renal function 1.

Pharmacokinetic Principles

Aztreonam exhibits predictable pharmacokinetics 1, 4:

• Serum half-life: 1.7 hours in normal renal function (range 1.5-2.0 hours)
• Volume of distribution: 12.6 L (approximately extracellular fluid volume)
• Protein binding: 56% in healthy subjects 1, though may be lower (30%) in infected patients 2
• Renal excretion: 60-70% excreted unchanged in urine by 8 hours 1

The serum half-life increases to 1.6-8.9 hours in patients with renal impairment 2, necessitating dose adjustments.

Elderly Patients

Renal status is the major determinant of dosing in elderly patients, who commonly have diminished renal function. 1 Serum creatinine alone may not accurately reflect renal status in the elderly; therefore, creatinine clearance should be estimated and dosing adjusted accordingly 1.

Pediatric Dosing

Aztreonam should be administered intravenously to pediatric patients with normal renal function (insufficient data exist for intramuscular administration or dosing in pediatric renal impairment) 1:

• Mild to moderate infections: 30 mg/kg every 8 hours
• Moderate to severe infections: 30 mg/kg every 6-8 hours
• Maximum daily dose: 120 mg/kg/day 1

Aztreonam pharmacokinetics are comparable between adults and pediatric patients down to 9 months of age 1.

Duration of Therapy

Continue aztreonam for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication is obtained. 1 Persistent infections may require several weeks of treatment 1. For complicated intra-abdominal infections specifically, antimicrobial therapy should be limited to 4-7 days unless source control is difficult to achieve 5.

Common Pitfalls

• Never use doses smaller than indicated 1—inadequate dosing promotes resistance
• Do not rely solely on serum creatinine in elderly patients—always estimate creatinine clearance 1
• Remember the loading dose in renal impairment—failure to give a full initial dose delays achievement of therapeutic levels 1
• Aztreonam has no activity against gram-positive bacteria or anaerobes—concurrent therapy is required for mixed infections 4, 6