Ceftolozane/Tazobactam Dosing in Patients with Impaired Renal Function
The recommended dosing for ceftolozane/tazobactam in patients with impaired renal function requires specific dose adjustments based on creatinine clearance levels, with 750 mg every 8 hours for patients with CrCl 30-50 mL/min and 375 mg every 8 hours for patients with CrCl 15-29 mL/min. 1
Standard Dosing for Normal Renal Function
For patients with normal renal function (CrCl >50 mL/min), the standard dosing is:
- Complicated urinary tract infections and intra-abdominal infections: 1.5 g (1 g ceftolozane/0.5 g tazobactam) IV every 8 hours 1
- Hospital-acquired or ventilator-associated pneumonia: 3 g (2 g ceftolozane/1 g tazobactam) IV every 8 hours 1
Renal Impairment Dosing Adjustments
Ceftolozane/tazobactam requires specific dose adjustments based on creatinine clearance:
| Creatinine Clearance (CrCl) | Recommended Dose for Standard Indications |
|---|---|
| >50 mL/min | 1.5 g every 8 hours |
| 30-50 mL/min | 750 mg every 8 hours |
| 15-29 mL/min | 375 mg every 8 hours |
For patients with hospital-acquired or ventilator-associated pneumonia, the doses should be doubled compared to the standard indications 1, 2.
End-Stage Renal Disease (ESRD) with Hemodialysis
For patients with ESRD on intermittent hemodialysis:
- Loading dose: 500 mg/250 mg ceftolozane/tazobactam
- Maintenance dose: 100 mg/50 mg ceftolozane/tazobactam administered every 8 hours by 1-hour infusion 3
- For HABP/VABP patients with ESRD requiring hemodialysis, a higher dose of 1.5 g/0.75 g loading dose followed by 300 mg/150 mg maintenance dose every 8 hours is recommended 3
- Administer after hemodialysis on dialysis days 2
Clinical Considerations and Monitoring
- Ceftolozane and tazobactam are primarily eliminated by the kidneys, with approximately 66% and 56% reductions in exposure during hemodialysis, respectively 2
- Plasma exposure to ceftolozane/tazobactam increases as renal function declines, with 4.4-fold and 3.8-fold increases in AUC for ceftolozane and tazobactam respectively in patients with severe renal impairment 2
- Monitor renal function regularly during treatment, especially in patients with pre-existing renal impairment 4
Important Cautions
- Higher doses of tazobactam-containing products (like 4.5 g piperacillin/tazobactam) have been associated with increased risk of acute kidney injury in patients with pre-existing renal impairment 4
- Avoid underdosing in critically ill patients with augmented renal clearance, as this may lead to treatment failure against resistant pathogens 5
- For critically ill patients with normal renal function but high creatinine clearance (e.g., 180 mL/min/1.73 m²), higher doses may be needed to achieve therapeutic targets 5
Pediatric Considerations
Limited data exists for ceftolozane/tazobactam dosing in pediatric patients with renal impairment. A study in critically ill children suggests:
- Children with normal renal function: 35-40 mg/kg every 8 hours
- Children with severe acute kidney injury: 10 mg/kg every 8 hours
- Children on continuous renal replacement therapy with high effluent rates: 30 mg/kg every 8 hours 6
Proper dosing of ceftolozane/tazobactam in patients with renal impairment is critical to balance efficacy against resistant pathogens while minimizing the risk of toxicity from drug accumulation.