Ceftazidime-Avibactam Removal by Dialysis and Dosing Adjustments
Yes, both ceftazidime and avibactam are substantially removed by hemodialysis, with more than 50% of each drug cleared during a 4-hour dialysis session, necessitating post-dialysis supplemental dosing to maintain therapeutic concentrations. 1
Dialyzability of Ceftazidime-Avibactam
Both components are significantly dialyzable: During a 4-hour hemodialysis session, greater than 50% of administered ceftazidime and avibactam are removed from the circulation, requiring dose replacement after each dialysis session. 1
The predominantly renal clearance of both ceftazidime and avibactam makes dose adjustments mandatory in patients with estimated creatinine clearance ≤50 mL/min, including those on dialysis. 2
Intermittent Hemodialysis (IHD) Dosing Recommendations
Standard Post-Dialysis Regimen
Administer 2.5 g (ceftazidime 2 g/avibactam 0.5 g) immediately after each hemodialysis session (typically three times weekly for patients on thrice-weekly dialysis schedules). 1
For 72-hour interdialytic intervals, add a supplemental dose of 1.25 g at the 48-hour mark to maintain therapeutic concentrations throughout the extended interval. 1
Critical Timing Principle
Always administer ceftazidime-avibactam after hemodialysis completion, never before, to prevent immediate drug removal during the dialysis session and ensure adequate therapeutic levels. 3
This post-dialysis timing also facilitates directly observed therapy and avoids drug loss that would lead to subtherapeutic concentrations. 3
Pharmacodynamic Targets
The post-dialysis dosing regimen achieves trough ceftazidime concentrations exceeding four times the minimum inhibitory concentration (MIC) and maintains avibactam trough concentrations above the critical threshold of 1 μg/mL throughout the treatment period. 1
For ceftazidime alone (without avibactam), a 1 g post-dialysis dose achieves 100% time above MIC for pathogens with MIC ≤8 mg/L over both 48- and 72-hour interdialytic intervals, though 2 g doses provide higher safety margins. 4
Continuous Renal Replacement Therapy (CRRT/CVVHD) Dosing
For continuous venovenous hemodialysis (CVVHD), administer 2.5 g every 12 hours as 2-hour infusions to maintain consistent therapeutic concentrations. 1
This regimen maintains trough concentrations of both ceftazidime and avibactam above therapeutic thresholds throughout the dosing interval. 1
Prolonged Intermittent Renal Replacement Therapy (PIRRT)
Innovative Dosing Strategy
Administer 1.875 g every 24 hours with PIRRT scheduled every 48 hours (6-hour session beginning 12 hours after the previous dose on hemodialysis days). 5
This coordinated timing of drug administration and dialysis sessions maintains relatively stable drug concentrations with minimal differences between hemodialysis and non-hemodialysis days. 5
Importance of Dialysis Timing
- The scheduled time point for PIRRT during the dosing interval is as critical as the dose itself—beginning dialysis 12 hours after dosing allows adequate drug distribution before removal. 5
Peritoneal Dialysis
- No specific data are available for ceftazidime-avibactam dosing in peritoneal dialysis patients. Begin with the intermittent hemodialysis regimen and verify adequacy through therapeutic drug monitoring. 6
Therapeutic Drug Monitoring (TDM)
When to Monitor
Strongly consider TDM in all dialysis patients receiving ceftazidime-avibactam, particularly those who are critically ill, have variable residual renal function, or show unexpected clinical responses. 3, 7
TDM is essential for diagnosing ceftazidime-induced neurotoxicity, which occurs particularly in patients with renal insufficiency and can manifest as altered mental status, seizures, or encephalopathy. 7
Target Concentrations
- Maintain ceftazidime trough concentrations above the MIC of the target pathogen (ideally >4× MIC) and avibactam trough concentrations >1 μg/mL. 1
Common Pitfalls and How to Avoid Them
Never Reduce Individual Doses
Maintain standard dose amounts (2.5 g) while extending the dosing interval—do not reduce the milligram dose to 1.25 g or lower for routine dialysis dosing, as this compromises peak concentrations needed for concentration-dependent bacterial killing. 3
The exception is the supplemental mid-interval dose (1.25 g at 48 hours) during 72-hour interdialytic periods. 1
Avoid Pre-Dialysis Administration
- Pre-dialysis dosing results in immediate drug removal and subtherapeutic levels, leading to treatment failure. 3
Recognize Neurotoxicity Risk
Ceftazidime accumulation in dialysis patients can cause neurotoxicity even with "appropriate" dosing based on product labeling—inferior cure rates have been documented when dose adjustments follow standard product information without TDM guidance. 7
Maintain high clinical suspicion for neurotoxicity (confusion, myoclonus, seizures) and obtain urgent ceftazidime levels if neurological symptoms develop. 7
Adjust for Residual Renal Function
- Pediatric and adult dosing recommendations use equivalent adjustments in dose quantity and/or administration interval based on estimated creatinine clearance, with more aggressive reductions required as renal function declines. 2