What is the recommended dose of ceftazidime-avibactam for a patient with Impaired renal function on hemodialysis (HD)?

Ceftazidime-Avibactam Dosing for Patients on Hemodialysis

For patients on hemodialysis, the recommended dose of ceftazidime-avibactam is 0.94 g (0.75 g ceftazidime and 0.19 g avibactam) administered after hemodialysis on dialysis days. 1

Pharmacokinetics and Rationale for Dosing

• Ceftazidime and avibactam are both primarily eliminated by the kidneys, with approximately 80-90% of ceftazidime and 97% of avibactam excreted unchanged in the urine 1
• Hemodialysis significantly affects the clearance of both drugs:
  • Approximately 55% of avibactam is removed during a 4-hour hemodialysis session 1
  • Similarly, about 55% of ceftazidime is removed during hemodialysis, with dialyzer clearance of 55.6 ml/min 2
• The elimination half-life of ceftazidime is significantly prolonged in patients with renal impairment, from approximately 1.5-2 hours in normal renal function to 33.6 hours in patients with end-stage renal disease 2, 3

Administration Timing

• Ceftazidime-avibactam should be administered after hemodialysis to:
  • Avoid premature removal of the drug during dialysis 1
  • Facilitate directly observed therapy (DOT) 4
  • Ensure adequate drug concentrations during the interdialytic period 5

Dosing for Different Interdialytic Intervals

• For standard 48-hour interdialytic intervals:
  • The 0.94 g dose administered post-hemodialysis provides adequate coverage for organisms with MICs ≤8 μg/ml 5, 6
• For extended 72-hour interdialytic intervals:
  • Some studies suggest higher doses may be needed for extended intervals 7, 6
  • Consider monitoring drug levels if available for patients with extended interdialytic intervals 5

Special Considerations

• Monitoring renal function is essential as ceftazidime-avibactam exposure is highly dependent on renal function 1
• For critically ill hemodialysis patients with severe infections or when treating resistant organisms (MICs 16-32 μg/ml), some studies suggest daily dosing of 500 mg to 1 g ceftazidime may provide better target attainment 6
• When treating bloodstream infections due to carbapenem-resistant Enterobacteriaceae (CRE), ceftazidime-avibactam is recommended as an effective option 4

Potential Adverse Effects

• Monitor for signs of neurotoxicity, especially in patients with fluctuating renal function 4
• Ceftazidime has been reported to be well-tolerated in hemodialysis patients, with only mild adverse effects such as pruritus reported in clinical studies 5

Remember that appropriate dosing of antimicrobials in hemodialysis patients is crucial to ensure both efficacy against target pathogens and prevention of toxicity due to drug accumulation.