Zavicefta Dosing for Newly Initiated RRT
For patients newly initiated on renal replacement therapy (RRT), administer Zavicefta (ceftazidime-avibactam) 0.94 grams (ceftazidime 0.75 grams and avibactam 0.19 grams) intravenously over 2 hours after each hemodialysis session, with dosing frequency determined by the hemodialysis schedule. 1
Specific Dosing by RRT Modality
Intermittent Hemodialysis
- Administer 0.94 grams after each hemodialysis session 1
- Both ceftazidime and avibactam are extensively removed by hemodialysis, with avibactam having an extraction coefficient of 0.77 and approximately 55% of the dose removed during a 4-hour hemodialysis session 1
- The drug must be given post-dialysis to prevent premature removal and facilitate directly observed therapy 2
- For patients dialyzing three times weekly, this translates to dosing every 48 hours on dialysis days 1
Continuous Renal Replacement Therapy (CRRT)
- Standard dosing recommendations do not adequately address CRRT scenarios 3
- The sieving coefficient for ceftazidime during CVVH and CVVHD is approximately 0.93, indicating high clearance by these modalities 4
- Therapeutic drug monitoring is strongly recommended to guide dosing in CRRT patients, as standard renal-adjusted doses may result in subtherapeutic levels 3
- Consider maintaining higher doses (closer to standard dosing) with therapeutic drug monitoring rather than using the reduced renal-adjusted doses 3, 5
Critical Dosing Principles
Maintain the 4:1 Ratio
- Always maintain the 4:1 ratio of ceftazidime to avibactam regardless of dose adjustment 6
- The linear relationship between drug clearance and creatinine clearance is similar for both components, supporting proportional dose reductions 6
Timing Considerations
- Administer all doses over 2 hours by intravenous infusion 1
- For hemodialysis patients, dosing must occur after dialysis completion to avoid drug removal 1
Monitoring Requirements
Essential Monitoring Parameters
- Monitor renal function (creatinine clearance) at least daily in patients with changing renal status 1
- Adjust dosing accordingly as renal function fluctuates 1
- Consider therapeutic drug monitoring, particularly in CRRT patients, to ensure adequate drug exposure while avoiding neurotoxicity 3
Neurotoxicity Risk
- Ceftazidime accumulation in renal impairment increases risk of neurotoxicity, including seizures, encephalopathy, and altered mental status 3
- Neurotoxicity is particularly concerning when standard renal-adjusted doses are used without therapeutic drug monitoring 3
Common Pitfalls to Avoid
Underdosing in RRT
- Renal-adjusted doses recommended in the FDA label may result in inadequate drug exposure and have been independently associated with increased mortality in serious infections 5
- In a retrospective study of KPC-producing Klebsiella pneumoniae bloodstream infections, renal-adjusted dosing (median 1.9 g daily) was independently associated with mortality (HR 4.47,95% CI 1.09-18.03) 5
Dosing Before Dialysis
- Never administer Zavicefta before hemodialysis, as over 50% of the dose will be removed during the dialysis session 1, 6
- This error results in subtherapeutic levels and treatment failure 1
Ignoring CRRT Clearance
- CRRT provides substantial drug clearance that may exceed residual renal function 4
- The contribution of CRRT to total ceftazidime clearance is higher in anuric patients than in those with residual renal function 4
- Standard renal-adjusted doses may be insufficient for patients on CRRT 3, 4
Practical Algorithm for RRT Patients
- Determine RRT modality: intermittent hemodialysis versus CRRT 1, 3
- For intermittent hemodialysis: Use 0.94 grams after each dialysis session 1
- For CRRT: Consider therapeutic drug monitoring and potentially higher doses than standard renal-adjusted recommendations 3
- Monitor daily: Assess renal function and clinical response 1
- Watch for neurotoxicity: Altered mental status, seizures, or encephalopathy warrant immediate evaluation and potential dose adjustment 3