Ceftazidime-Avibactam Dosing for CrCl 34 mL/min
For a patient with CrCl 34 mL/min, administer ceftazidime-avibactam 1.25 g (1000 mg ceftazidime/250 mg avibactam) IV every 12 hours, infused over 2 hours. 1, 2
Renal Dose Adjustment Algorithm
The standard dose of 2.5 g IV every 8 hours is only appropriate for patients with CrCl >50 mL/min 3. Your patient with CrCl 34 mL/min falls into the moderate renal impairment category (CrCl 31-50 mL/min), requiring dose reduction 1, 2.
Specific Dosing by Renal Function:
- CrCl >50 mL/min: 2.5 g (2000 mg/500 mg) IV every 8 hours 3, 2
- CrCl 31-50 mL/min: 1.25 g (1000 mg/250 mg) IV every 12 hours 1, 2
- CrCl 16-30 mL/min: 0.94 g (750 mg/187.5 mg) IV every 12 hours 1
- CrCl 6-15 mL/min: 0.94 g (750 mg/187.5 mg) IV every 24 hours 1
- CrCl <5 mL/min or hemodialysis: 0.94 g (750 mg/187.5 mg) IV every 48 hours, administered after hemodialysis on dialysis days 1
Pharmacokinetic Rationale
Both ceftazidime and avibactam are predominantly renally cleared, with approximately 80% of ceftazidime and similar proportions of avibactam eliminated unchanged in urine 1, 4. The clearance of both drugs demonstrates a linear relationship with creatinine clearance, necessitating proportional dose adjustments to maintain therapeutic exposures while avoiding accumulation 1, 2.
The 4:1 ratio of ceftazidime to avibactam is maintained across all renal dosing adjustments because both drugs have similar renal clearance patterns 1.
Infusion Duration
Administer the dose over 2 hours by IV infusion 2. For severe infections or augmented renal clearance scenarios, extended infusion times of 3-4 hours may optimize PK/PD target attainment, though this is not standard for moderate renal impairment 5.
Monitoring Requirements
- Renal function monitoring: Assess creatinine clearance regularly during therapy, as changes in renal function require dose adjustment 3, 1
- Calculate CrCl using Cockcroft-Gault formula for dose determination 3, 2
- Monitor for signs of drug accumulation if renal function deteriorates further 1
Duration by Indication
The dose adjustment applies regardless of infection type, but treatment duration varies 3:
- Complicated UTI/pyelonephritis: 7-14 days 6
- Complicated intra-abdominal infections (with metronidazole): 5-14 days 3, 6
- Bloodstream infections: 7-14 days 3
- Hospital-acquired/ventilator-associated pneumonia: 7-14 days 6
Critical Caveats
Hemodialysis consideration: If your patient progresses to requiring hemodialysis, ceftazidime-avibactam must be administered after dialysis sessions, as >50% of the drug is removed during a 4-hour hemodialysis session 1.
Combination therapy for intra-abdominal infections: Add metronidazole 500 mg IV every 6-8 hours for anaerobic coverage when treating complicated intra-abdominal infections 3, 6.