Aztreonam Renal Dose Modification
For patients with renal impairment, aztreonam requires dose reduction based on creatinine clearance: halve the dose for CrCl 10-30 mL/min/1.73m² after a full loading dose, and reduce to one-fourth the usual dose for CrCl <10 mL/min (including hemodialysis patients), with an additional one-eighth dose after each dialysis session. 1
Dosing Algorithm by Renal Function
Normal Renal Function (CrCl >30 mL/min/1.73m²)
- Standard dosing: 500 mg to 2 g every 6-12 hours depending on infection severity 1
- No dose adjustment required 1
- Serum half-life: 1.5-2.1 hours 2
Moderate Renal Impairment (CrCl 10-30 mL/min/1.73m²)
- Loading dose: Give full initial dose of 1 g or 2 g 1
- Maintenance dose: Reduce to 50% of usual dose at standard intervals (every 6,8, or 12 hours) 1
- Example: If usual dose is 2 g every 8 hours, give 2 g loading dose, then 1 g every 8 hours 1
Severe Renal Impairment (CrCl <10 mL/min/1.73m²)
- Loading dose: Give full initial dose of 500 mg, 1 g, or 2 g 1
- Maintenance dose: Reduce to 25% (one-fourth) of usual initial dose at standard intervals 1
- Example: If usual dose is 2 g every 8 hours, give 2 g loading dose, then 500 mg every 8 hours 1
Hemodialysis Patients
- Loading dose: Give full initial dose 1
- Maintenance dose: One-fourth of usual dose at standard intervals 1
- Post-dialysis supplementation: Give one-eighth of initial dose after each hemodialysis session 1
- Administer supplemental dose after dialysis to facilitate directly observed therapy and avoid premature drug removal 3
Estimating Creatinine Clearance
When only serum creatinine is available, use the Cockcroft-Gault formula 1:
Males: CrCl = [weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]
Females: 0.85 × male calculation 1
The serum creatinine must represent steady-state renal function 1.
Clinical Pharmacology Supporting Dose Adjustments
- Renal elimination: Aztreonam is primarily eliminated unchanged in urine, making renal function the major determinant of clearance 2, 4
- Clearance correlation: Aztreonam clearance correlates strongly with creatinine clearance (r² = 0.90), with a mean CL/CrCl ratio of 1.11 4
- Half-life prolongation: In patients with renal impairment, half-life extends from 1.6 hours (normal function) to 8.9 hours (moderate impairment) 4
- Pharmacodynamic validation: Population pharmacokinetic modeling confirms >90% probability of target attainment with FDA-recommended dose adjustments for moderate and severe renal impairment 5
Special Considerations for Elderly Patients
- Renal status is critical: Elderly patients frequently have diminished renal function that may not be reflected accurately by serum creatinine alone 1
- Always estimate CrCl: Obtain creatinine clearance estimates rather than relying on serum creatinine, as this is a major determinant of dosage in the elderly 1
- Safety profile: Aztreonam has proven safe in elderly patients with diminished renal function when appropriately dosed 6
Metabolite Accumulation
- SQ 26,992 metabolite: Aztreonam is hydrolyzed to an inactive metabolite (SQ 26,992) that accumulates in renal impairment 6
- Accumulation pattern: The metabolite accumulation ratio is inversely related to creatinine clearance (r = -0.89) 6
- Clinical significance: Despite metabolite accumulation, no adverse clinical reactions or laboratory abnormalities have been detected with appropriate dosing 6
Key Clinical Pitfalls
- Do not use smaller doses than indicated: Reduced doses below recommendations may compromise efficacy, particularly against Pseudomonas aeruginosa 1
- Loading dose is essential: Always give the full loading dose regardless of renal function to achieve rapid therapeutic levels 1
- Monitor for accumulation: Prolonged serum levels occur with transient or persistent renal insufficiency 1
- Avoid nephrotoxic combinations: Unlike aminoglycosides, aztreonam is not nephrotoxic, making it a safer alternative in patients with renal compromise 2, 7