Ceftazidime-Avibactam IV Dilution and Administration
Ceftazidime-avibactam should be administered as 2.5 grams (2000 mg ceftazidime + 500 mg avibactam) infused intravenously over 2 hours every 8 hours for patients with normal renal function (creatinine clearance >50 mL/min). 1, 2, 3
Standard Dilution and Infusion Protocol
The recommended administration method is a 2-hour intravenous infusion every 8 hours, which has been validated through extensive pharmacokinetic/pharmacodynamic modeling and clinical trials. 2, 3
- The standard adult dose is 2.5 g (2000 mg ceftazidime + 500 mg avibactam) administered every 8 hours via 2-hour IV infusion 1, 2
- This dosing regimen achieves optimal pharmacodynamic targets with >95% target attainment against MICs ≤8 mg/L regardless of patient factors including obesity, older age, or augmented renal clearance 2
Renal Dose Adjustments
Dosage modifications are required for patients with creatinine clearance ≤50 mL/min, as both ceftazidime and avibactam are renally eliminated. 2
- Patients with CLCR >50 mL/min: Standard dose of 2.5 g every 8 hours 2
- Modified dosing regimens exist for CLCR ≤50 mL/min, though specific adjustments should follow manufacturer guidelines 2
Pediatric Dosing Considerations
For pediatric patients, weight-based dosing is recommended with maximum dose limits:
- Children ≥6 months: 50 mg/kg/dose (ceftazidime component) IV every 8 hours 4
- Maximum dose: 2000 mg ceftazidime per dose 4
- Children 3 to <6 months: 40 mg/kg/dose IV every 8 hours 4
Alternative Administration: Continuous Infusion
Continuous infusion (CI) represents an emerging alternative administration strategy, though it is not yet FDA-approved and requires therapeutic drug monitoring. 5
- CI dosing of 5 g every 12 hours has shown promising results in small case series 5
- This approach requires therapeutic drug monitoring with target ceftazidime levels of ≥4-5 × MIC in plasma 5
- CI achieved clinical cure in 80% and microbiological eradication in 90% of cases in one retrospective series 5
- This approach should only be used with therapeutic drug monitoring capabilities and infectious disease consultation 5
Critical Pharmacodynamic Principles
The efficacy of ceftazidime-avibactam depends on maintaining adequate concentrations of both components simultaneously:
- Ceftazidime target: 50% free time above the MIC 2
- Avibactam target: free time above a critical threshold concentration of 1 mg/L 2
- The 2-hour infusion over 8-hour dosing interval optimally achieves these joint pharmacodynamic targets 2
Common Pitfalls to Avoid
Do not administer as a rapid IV push or short infusion (<2 hours), as this fails to optimize the time-dependent killing characteristics of beta-lactams and may compromise avibactam's ability to maintain adequate inhibitory concentrations throughout the dosing interval. 2
- Avoid extending the dosing interval beyond 8 hours in patients with normal renal function, as avibactam concentrations may drop below the critical 1 mg/L threshold needed for beta-lactamase inhibition 6
- Do not use standard ceftazidime dosing without the avibactam component for resistant organisms, as ceftazidime alone has no effect against beta-lactamase-producing pathogens 6