Aztreonam Dosing in Adults
For adults with normal renal function, aztreonam should be dosed at 1-2 grams IV/IM every 8 hours for moderately severe systemic infections, or 2 grams every 6-8 hours for severe or life-threatening infections, with the maximum recommended dose being 8 grams per day. 1
Standard Dosing by Infection Severity
The FDA-approved dosing regimen varies by infection type and severity 1:
- Urinary tract infections: 500 mg to 1 g every 8-12 hours 1
- Moderately severe systemic infections: 1-2 g every 8-12 hours 1
- Severe systemic or life-threatening infections: 2 g every 6-8 hours 1
For Pseudomonas aeruginosa infections specifically, 2 grams every 6-8 hours is recommended at least upon initiation of therapy due to the serious nature of these infections. 1
Route of Administration
- Intravenous route is recommended for patients requiring single doses greater than 1 gram or those with bacterial septicemia, localized parenchymal abscess, peritonitis, or other severe systemic or life-threatening infections 1
- Intramuscular administration is acceptable for less severe infections 1, 2
Dosing in Renal Impairment
Aztreonam requires dose adjustment in renal impairment because prolonged serum levels occur with reduced creatinine clearance. 1 The correlation between aztreonam clearance and creatinine clearance is excellent (r² = 0.90), with a mean clearance/creatinine clearance ratio of 1.11 3
Dose Adjustment Algorithm 1:
Creatinine clearance 10-30 mL/min/1.73 m²:
- Give initial loading dose of 1-2 g
- Then reduce maintenance dose to half the usual dose at the usual interval (every 6,8, or 12 hours)
Creatinine clearance <10 mL/min/1.73 m² (including hemodialysis patients):
- Give usual initial dose (500 mg, 1 g, or 2 g)
- Maintenance dose: one-fourth of the usual initial dose at the usual interval
- For serious/life-threatening infections: Give one-eighth of the initial dose after each hemodialysis session in addition to maintenance doses
Estimating Creatinine Clearance 1:
When only serum creatinine is available:
- Males: CLcr = [weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]
- Females: 0.85 × male calculation
The serum creatinine must represent steady-state renal function. 1
Duration of Therapy
Aztreonam should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication is obtained. 1, 4 Persistent infections may require several weeks of treatment 1, 4
Pharmacokinetic Considerations
- Half-life in normal renal function: 1.5-2.1 hours 2, 5
- Half-life in renal impairment: Can extend to 8.9 hours 3
- Volume of distribution: Approximately 0.16 L/kg, approximating extracellular fluid volume 3
- Primary elimination: Urinary excretion 2, 5
- No significant accumulation occurs with multiple dosing in patients with appropriate dose adjustments 3
Special Populations
Elderly patients require particular attention to renal function, as serum creatinine may not accurately reflect renal status 1. Creatinine clearance estimates should be obtained and dosage modifications made accordingly 1. Aztreonam has been shown to be both effective and safe in elderly patients, even those with impaired renal function, with creatinine clearance remaining stable or improving during treatment 6
Critical Combination Therapy
For metallo-β-lactamase-producing carbapenem-resistant Enterobacterales (CRE), combine aztreonam 1-2 grams IV every 6-8 hours with ceftazidime-avibactam, as this combination showed significantly lower 30-day mortality (19.2% vs 44%, P=0.007) compared to other agents 7
Important Clinical Caveats
- Do not use doses smaller than indicated 1
- The strictly gram-negative aerobic spectrum limits aztreonam's use as a single empiric agent 2, 5
- Concurrent therapy with other antimicrobials is recommended before causative organisms are identified in seriously ill patients at risk for gram-positive or anaerobic infections 2, 5
- Aztreonam is not nephrotoxic and represents a good alternative to aminoglycosides, particularly in patients with renal impairment 2, 6