What are the renal dose modifications for Ceftazidime (Ceftazidime)-Avibactam and Aztreonam in patients with impaired renal function?

Renal Dose Modifications for Ceftazidime-Avibactam and Aztreonam

Both ceftazidime-avibactam and aztreonam require dose reductions in patients with renal impairment, as both are primarily eliminated by glomerular filtration and their clearance correlates directly with creatinine clearance.

Ceftazidime-Avibactam Dosing in Renal Impairment

Standard Dosing (Normal Renal Function)

• Adults with CrCl >50 mL/min: 2.5 g (2 g ceftazidime/0.5 g avibactam) IV every 8 hours as a 2-hour infusion 1
• The 4:1 ratio of ceftazidime to avibactam must be maintained across all dose adjustments 2, 1

Dose Adjustments Based on Creatinine Clearance

For CrCl 31-50 mL/min (Mild-Moderate Impairment):

• Reduce to 1.25 g (1 g/0.25 g) IV every 12 hours 3, 1

For CrCl 16-30 mL/min (Moderate-Severe Impairment):

• Reduce to 0.94 g (0.75 g/0.19 g) IV every 24 hours 3

For CrCl 6-15 mL/min (Severe Impairment):

• Reduce to 0.94 g (0.75 g/0.19 g) IV every 48 hours 3

For CrCl <5 mL/min or End-Stage Renal Disease on Hemodialysis:

• Administer after hemodialysis, as >50% of avibactam is removed during a 4-hour dialysis session 2
• Dosing should follow the severe impairment schedule with administration timed post-dialysis 2

Key Pharmacokinetic Considerations

• Both ceftazidime and avibactam have similar half-lives (~2 hours in normal renal function) that increase proportionally with declining renal function 1
• The linear relationship between drug clearance and CrCl is comparable for both components, justifying the fixed 4:1 ratio across all renal function levels 2
• Avibactam exposure (AUC) and terminal half-life increase progressively with worsening renal impairment 2

Aztreonam Dosing in Renal Impairment

Standard Dosing (Normal Renal Function)

• Moderate systemic infections: 1-2 g IV every 8-12 hours 4
• Severe/life-threatening infections: 2 g IV every 6-8 hours 4

Dose Adjustments Based on Creatinine Clearance

For CrCl 10-30 mL/min/1.73 m²:

• Give usual loading dose (1-2 g), then reduce maintenance dose by 50% at the usual interval (every 6,8, or 12 hours) 4

For CrCl <10 mL/min/1.73 m² (Including Hemodialysis):

• Give usual loading dose (500 mg, 1 g, or 2 g) 4
• Maintenance dose: one-fourth of the usual initial dose at the usual interval 4
• For serious/life-threatening infections: Add one-eighth of the initial dose after each hemodialysis session 4

Calculating Creatinine Clearance

When only serum creatinine is available, use the Cockcroft-Gault equation 4:

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

Critical Clinical Considerations

Monitoring Requirements

• Obtain baseline creatinine clearance before initiating therapy 5, 4
• Serum creatinine should represent steady-state renal function 4
• For ceftazidime-avibactam, monitor for accumulation in severe renal impairment 2

Common Pitfalls to Avoid

• Do not use smaller doses than recommended for aztreonam, as this reduces efficacy 4
• Always give loading doses in renal impairment before reducing maintenance doses 4
• Time hemodialysis appropriately: Administer both drugs after dialysis to avoid premature drug removal 4, 2
• For aztreonam in pediatric patients, there are insufficient data for dosing in renal impairment—use adult extrapolation cautiously 4

Special Populations

• Elderly patients: May have diminished renal function not reflected by serum creatinine alone; always calculate CrCl rather than relying on creatinine values 4
• Pediatric patients ≥3 months with renal impairment: Ceftazidime-avibactam dose adjustments use equivalent reductions in dose quantity and/or interval as adults, normalized to body surface area 3

Duration of Therapy

• Continue treatment for at least 48 hours after clinical improvement or bacterial eradication 5, 4
• Complicated infections may require several weeks of therapy 4