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 2-3 hours reserved only for those with CrCl >50 mL/min. 1, 2
Standard Dosing (Normal Renal Function)
- CrCl >50 mL/min: 2.5 g (2000 mg ceftazidime + 500 mg avibactam) IV every 8 hours, infused over 2-3 hours 1, 2
- This dosing applies across all approved indications including CRE bloodstream infections, complicated urinary tract infections, and complicated intra-abdominal infections 1
Dose Adjustments for Renal Impairment
Critical principle: Both ceftazidime and avibactam are eliminated almost exclusively by the kidneys, making dose adjustment essential to prevent drug accumulation and neurotoxicity 2, 3
Moderate Renal Impairment (CrCl 31-50 mL/min)
- Avibactam exposure increases 3.8-fold compared to normal renal function 2
- Dose reduction is mandatory, though specific adjusted doses should follow FDA labeling recommendations 2
Severe Renal Impairment (CrCl ≤30 mL/min, not on dialysis)
- Avibactam exposure increases 7-fold compared to normal renal function 2
- Substantial dose reduction required 2
End-Stage Renal Disease (ESRD) on Hemodialysis
- Avibactam exposure increases 19.5-fold when given post-dialysis 2
- Administer ceftazidime-avibactam AFTER hemodialysis, as approximately 55% of avibactam is removed during a 4-hour dialysis session 2, 3
- The hemodialysis extraction coefficient is 0.77, with mean clearance of 9.0 L/h 2
Monitoring Requirements
Monitor renal function at least daily in all patients receiving ceftazidime-avibactam and adjust dosing accordingly 2
Key Safety Considerations
- Neurotoxicity risk: Watch for seizures, encephalopathy, and confusion, particularly in patients with renal impairment where beta-lactam accumulation occurs 4
- Ceftazidime has lower pro-convulsive activity than some other beta-lactams, but vigilance remains essential 4
- The linear relationship between avibactam clearance and CrCl parallels that of ceftazidime, supporting the maintained 4:1 ratio across all renal function levels 3
Pediatric Considerations
- For pediatric patients ≥2 years with renal impairment: dose adjustments follow similar principles based on estimated glomerular filtration rate (eGFR) 2
- Insufficient data exist for dose recommendations in children <2 years with renal impairment 2
Infusion Duration Considerations
- Standard infusion time is 2 hours 5, 6
- For severe infections or augmented renal clearance, extending infusion to 3-4 hours may be necessary to achieve higher pharmacodynamic targets (100% fT≥MIC) 7
- The 2022 guidelines specifically recommend 3-hour infusions for CRE bloodstream infections 1
Common Pitfalls to Avoid
- Never use standard dosing in moderate-to-severe renal impairment: The dramatic increases in drug exposure (up to 19.5-fold in ESRD) create substantial toxicity risk 2
- Do not administer before hemodialysis: Over 50% will be removed during dialysis, resulting in subtherapeutic levels 2, 3
- Do not assume hepatic dysfunction requires adjustment: Neither drug undergoes significant hepatic metabolism 2