Ceftazidime-Avibactam Dosing for Adults with Normal Renal Function
For adults with normal renal function (CrCL >50 mL/min) and no beta-lactam allergy, administer ceftazidime-avibactam 2.5 grams (ceftazidime 2 grams + avibactam 0.5 grams) intravenously every 8 hours as a 2-hour infusion. 1, 2
Standard Dosing Parameters
- The fixed-dose combination maintains a 4:1 ratio of ceftazidime to avibactam, which is pharmacokinetically optimized based on their complementary elimination profiles with similar half-lives of approximately 2 hours 3, 4
- Both components are primarily eliminated renally, with ceftazidime showing 80-90% unchanged urinary excretion and avibactam demonstrating 97% urinary recovery 2
- The 2-hour infusion duration is critical for achieving optimal pharmacodynamic targets 1, 2
Indication-Specific Duration
- Complicated urinary tract infections (cUTI) including pyelonephritis: 7-14 days 1
- Complicated intra-abdominal infections (cIAI): 5-14 days, must be combined with metronidazole 500 mg IV every 6-8 hours for anaerobic coverage, as ceftazidime-avibactam lacks anaerobic activity 1
- Hospital-acquired/ventilator-associated pneumonia (HABP/VABP): 7-14 days 1
- Carbapenem-resistant Enterobacterales (CRE) bloodstream infections: Consider 3-hour infusions instead of 2-hour infusions to optimize time-dependent pharmacodynamics 1
Pharmacodynamic Optimization Strategies
- For infections with high-MIC organisms (MIC ≥4 mg/L), prolonged infusions of 3-4 hours may improve efficacy by maximizing time above MIC 1
- The pharmacodynamic targets are: ceftazidime free drug concentration >8 mg/L and avibactam >1 mg/L for ≥50% of the dosing interval 3, 4, 5
- Probability of target attainment exceeds 94.9% across all patient subgroups with the standard dosing regimen 4
Critical Combination Therapy Scenarios
- For metallo-β-lactamase-producing CRE: Combine with aztreonam 1-2 grams IV every 6-8 hours, as avibactam does not inhibit metallo-β-lactamases 1
- This combination demonstrated significantly lower 30-day mortality (19.2% vs 44%, P=0.007) compared to other agents 1
- For KPC-3 producing organisms: Consider adding a carbapenem or colistin to prevent resistance emergence, particularly in patients with prior ceftazidime-avibactam exposure 1
Important Clinical Caveats
- Prior ceftazidime-avibactam use is a major risk factor for resistance development in KPC-producing organisms 1
- Obtain antimicrobial susceptibility testing and determine carbapenemase type before initiating therapy when possible 1
- Ceftazidime has relatively low pro-convulsive activity (17% relative to penicillin G = 100%), though neurotoxicity risk increases when plasma concentrations exceed 8 times the MIC 1
- No dose adjustment is needed for obesity, older age, or augmented renal clearance in patients with CrCL >50 mL/min 5
- Steady-state is achieved without appreciable accumulation after multiple doses 2
Renal Function Monitoring
- While the question specifies normal renal function, dose adjustments are mandatory when CrCL drops to ≤50 mL/min due to the predominantly renal elimination of both components 2, 6, 7
- The linear relationship between drug clearance and creatinine clearance necessitates maintaining the 4:1 ratio even with dose reductions 7, 3