Zavicefta (Ceftazidime/Avibactam) in Liver Failure
No dose adjustment of Zavicefta is required for patients with hepatic impairment of any severity (Child-Pugh A, B, or C), as both ceftazidime and avibactam are eliminated renally with negligible hepatic metabolism. 1
Pharmacokinetic Basis for Dosing
Zavicefta does not require hepatic dose adjustment because:
- Ceftazidime pharmacokinetics are unaffected by hepatic dysfunction, as demonstrated in patients receiving 2 grams IV every 8 hours for 5 days 1
- Avibactam does not undergo significant hepatic metabolism and its systemic clearance is not expected to be affected by hepatic impairment 1
- Renal clearance is the primary elimination pathway for both components, with avibactam showing a renal clearance of 158 mL/min (exceeding glomerular filtration, indicating active tubular secretion) 1
- An average of 85% of administered avibactam is recovered unchanged in urine within 96 hours 1
Standard Dosing Across All Child-Pugh Classes
For patients with normal renal function (CrCl >50 mL/min), regardless of hepatic impairment severity:
- Administer 2.5 grams (2000 mg ceftazidime/500 mg avibactam) IV every 8 hours as a 2-hour infusion 1, 2
- This applies equally to Child-Pugh A, B, and C patients 1
Critical Renal Function Monitoring
The key consideration in cirrhotic patients is renal function, not hepatic function:
- Monitor creatinine clearance at least daily, as both drug exposures are highly dependent on renal function 1
- Dose adjustment is required for moderate renal impairment (CrCl 31-50 mL/min), severe renal impairment (CrCl 6-30 mL/min), and end-stage renal disease 1
- Cirrhotic patients are at high risk for hepatorenal syndrome and acute kidney injury, which necessitate dose adjustment 3
Evidence Supporting Use in Cirrhosis
Real-world data demonstrates favorable outcomes in cirrhotic patients:
- In a cohort of 39 cirrhotic patients (median MELD 16) with carbapenem-resistant Klebsiella pneumoniae infections, ceftazidime-avibactam therapy was associated with significantly lower treatment failure rates (7% vs 38%, P=0.032) compared to other regimens 3
- This benefit was independent of Child-Pugh class and whether monotherapy or combination therapy was used 3
- In-hospital survival improved with ceftazidime-avibactam therapy (log rank P=0.035) after adjusting for Child class 3
Practical Algorithm for Dosing
Step 1: Assess renal function (not hepatic function)
- Calculate CrCl in adults or eGFR in pediatric patients 1
Step 2: Apply dosing based solely on renal function:
- CrCl >50 mL/min: 2.5 grams IV every 8 hours over 2 hours 1
- CrCl 31-50 mL/min: 1.25 grams IV every 8 hours over 2 hours 1
- CrCl 16-30 mL/min: 0.94 grams IV every 12 hours over 2 hours 1
- CrCl 6-15 mL/min: 0.94 grams IV every 24 hours over 2 hours 1
- ESRD on hemodialysis: Administer after hemodialysis, as approximately 55% is removed during a 4-hour session 1, 4
Step 3: Monitor for complications specific to cirrhosis:
- Watch for hepatorenal syndrome development requiring dose adjustment 3
- Monitor for acute-on-chronic liver failure, which was more common in treatment failure cases 3
Common Pitfalls to Avoid
Do not reduce the dose based on hepatic impairment alone - this is unnecessary and may lead to therapeutic failure, as hepatic dysfunction does not affect drug clearance 1, 5
Do not assume stable renal function in cirrhotic patients - daily monitoring is essential as these patients frequently develop acute kidney injury or hepatorenal syndrome during severe infections 1, 3
Do not delay treatment in severe cirrhosis - ceftazidime-avibactam has demonstrated efficacy even in decompensated cirrhosis and should be considered first-line for carbapenem-resistant infections 3