Dosing of Ceftazidime-Avibactam and Aztreonam in Hemodialysis Patients
For patients on hemodialysis, ceftazidime-avibactam should be dosed at 0.94 grams (ceftazidime 0.75 grams and avibactam 0.19 grams) every 48 hours, administered after the hemodialysis session on dialysis days, while aztreonam should be administered as a standard loading dose followed by one-fourth the loading dose at standard intervals, with a supplemental dose equal to half the maintenance dose after each dialysis session. 1, 2
Ceftazidime-Avibactam Dosing in Hemodialysis
FDA-Approved Dosing
- For patients with end-stage renal disease on hemodialysis (creatinine clearance ≤5 mL/min), the recommended dose of ceftazidime-avibactam is 0.94 grams (ceftazidime 0.75 grams and avibactam 0.19 grams) administered intravenously every 48 hours 1
- Both ceftazidime and avibactam are hemodialyzable; therefore, administer ceftazidime-avibactam after hemodialysis on hemodialysis days 1
- Avibactam is extensively removed by hemodialysis, with an extraction coefficient of 0.77 and a mean hemodialysis clearance of 9.0 L/h 1
- Approximately 55% of the avibactam dose is removed during a 4-hour hemodialysis session 1, 3
Pharmacokinetic Considerations
- Ceftazidime is eliminated almost solely by the kidneys; its serum half-life is significantly prolonged in patients with impaired renal function 1
- A 4-hour hemodialysis procedure reduces the elimination half-life of ceftazidime from 33.6 hours to 3.3 hours 4
- Approximately 55% of administered ceftazidime is recovered in the dialysate fluid during hemodialysis 4
- The clearance of avibactam is significantly decreased in patients with severe renal impairment or end-stage renal disease, resulting in up to 19.5-fold increase in systemic exposure compared to patients with normal renal function 1
Aztreonam Dosing in Hemodialysis
Recommended Dosing
- For hemodialysis patients, aztreonam should be administered as a standard loading dose, followed by one-fourth the loading dose at standard dose intervals 2
- A supplemental dose equal to half the usual maintenance dose should be given immediately after each dialysis session 2
- Hemodialysis removes approximately 38.2% (range 27-58%) of aztreonam during a 4-hour session 2
- The serum half-life of aztreonam is 7.9 hours between dialysis sessions and decreases to 2.7 hours during dialysis 2
Clinical Considerations and Monitoring
- For both medications, monitor for signs of efficacy and toxicity, as altered pharmacokinetics in hemodialysis patients may affect both therapeutic outcomes and adverse effects 1, 2
- When treating catheter-related bloodstream infections in hemodialysis patients, empirical antibiotic therapy should include coverage for gram-negative bacilli based on local antibiogram data 5
- For patients with hemodialysis-related infections, preference should be given to antibiotics that can be administered during hemodialysis treatments 5
- Surveillance blood cultures should be obtained one week after completion of an antibiotic course if the catheter has been retained 5
Common Pitfalls to Avoid
- Failure to administer the antibiotics after (not before) hemodialysis sessions, which could result in significant drug removal and subtherapeutic levels 1, 4
- Not providing supplemental dosing after hemodialysis sessions, which is necessary to maintain adequate drug concentrations 4, 2
- Overlooking the need for dose adjustments based on renal function, which could lead to drug accumulation and potential toxicity 1, 3
- Using standard dosing regimens in hemodialysis patients, which may result in either underdosing or overdosing 1, 6
Remember that monitoring renal function at least daily and adjusting the dosage accordingly is crucial for patients with changing renal function to ensure optimal therapeutic outcomes while minimizing adverse effects 1.