Ceftazidime-Avibactam Dosing in Renal Impairment
For patients with impaired renal function, ceftazidime-avibactam requires dose reduction based on creatinine clearance (CrCl), with the standard dose of 2.5 g IV every 8 hours over 2 hours reserved only for patients with CrCl >50 mL/min. 1, 2
Standard Dosing (Normal Renal Function)
- Patients with CrCl >50 mL/min: Administer 2.5 g (ceftazidime 2 g + avibactam 0.5 g) IV every 8 hours as a 2-hour infusion 1, 2
- This standard regimen applies across all approved indications including complicated urinary tract infections, complicated intra-abdominal infections, hospital-acquired/ventilator-associated bacterial pneumonia, and carbapenem-resistant Enterobacteriaceae infections 1, 3
Renal Dose Adjustments (Adults)
The FDA-approved dosing adjustments for renal impairment are critical to prevent drug accumulation and neurotoxicity 1, 2:
- CrCl 31-50 mL/min: 1.25 g (ceftazidime 1 g + avibactam 0.25 g) IV every 8 hours 2
- CrCl 16-30 mL/min: 0.94 g (ceftazidime 0.75 g + avibactam 0.19 g) IV every 12 hours 2
- CrCl 6-15 mL/min: 0.94 g (ceftazidime 0.75 g + avibactam 0.19 g) IV every 24 hours 2
- CrCl ≤5 mL/min: 0.94 g (ceftazidime 0.75 g + avibactam 0.19 g) IV every 48 hours 2
All doses should be administered as 2-hour infusions 2, 4
Hemodialysis Considerations
- Both ceftazidime and avibactam are hemodialyzable, with approximately 55% of avibactam removed during a 4-hour dialysis session 1
- Administer the dose after hemodialysis on dialysis days to maintain therapeutic levels 1, 2
Continuous Renal Replacement Therapy (CRRT)
- For critically ill patients receiving continuous venovenous hemodiafiltration (CVVHDF), a dose of 2.5 g IV every 8 hours over 2 hours achieved appropriate pharmacokinetic targets in case reports 5
- This higher dosing is particularly important for pneumonia due to limited ceftazidime penetration into epithelial lining fluid 5
Critical Monitoring Requirements
Monitor for neurotoxicity vigilantly, especially in renal impairment 1, 6:
- Watch for seizures, encephalopathy, and confusion, which result from beta-lactam accumulation 1
- While ceftazidime has lower pro-convulsive activity than some other beta-lactams, the risk remains significant in renal dysfunction 1, 6
- Monitor CrCl at least daily in patients with changing renal function and adjust dosing accordingly 2, 7
Pharmacokinetic Rationale
- Renal clearance is the primary elimination pathway for both ceftazidime and avibactam, with both drugs having a half-life of approximately 2 hours in normal renal function 8
- The pharmacodynamic targets are: ceftazidime free concentration >8 mg/L for ≥50% of the dosing interval and avibactam free concentration >1 mg/L for ≥50% of the dosing interval 3, 4
- Population pharmacokinetic modeling demonstrates that CrCl is the key covariate determining clearance variability, necessitating dose adjustments 3, 7
Common Pitfalls to Avoid
- Do not use standard dosing in patients with CrCl ≤50 mL/min, as this leads to drug accumulation and increased neurotoxicity risk 1, 2
- Do not administer doses before hemodialysis, as significant drug removal occurs during dialysis 1, 2
- Do not assume stable renal function—daily monitoring is essential as rapidly improving renal function can lead to subtherapeutic exposures with overly conservative dosing 7