Ceftazidime-Avibactam Dosing for Adults with Normal Renal Function
For adults with normal renal function (creatinine clearance >50 mL/min), administer ceftazidime-avibactam 2.5 grams (ceftazidime 2 grams plus avibactam 0.5 grams) intravenously every 8 hours as a 2-hour infusion. 1, 2
Standard Dosing Regimen
The 2.5-gram dose (2 grams ceftazidime + 0.5 grams avibactam) every 8 hours over 2-3 hours is the FDA-approved standard for patients with CrCl >50 mL/min across all approved indications. 1, 2
This dosing regimen applies uniformly to complicated urinary tract infections, complicated intra-abdominal infections (when combined with metronidazole), hospital-acquired pneumonia, ventilator-associated pneumonia, and carbapenem-resistant Enterobacterales infections. 1, 3
The 2-hour infusion duration is critical for achieving optimal pharmacokinetic/pharmacodynamic targets, specifically maintaining free ceftazidime concentrations above the MIC for ≥50% of the dosing interval and free avibactam concentrations above 1 mg/L for ≥50% of the dosing interval. 4, 5
Pharmacokinetic Rationale
Both ceftazidime and avibactam have complementary half-lives of approximately 2 hours, making the 8-hour dosing interval appropriate for maintaining therapeutic concentrations. 5, 6
The 4:1 fixed-dose ratio (ceftazidime:avibactam) was specifically designed based on population pharmacokinetic modeling showing that this combination achieves joint probability of target attainment ≥94.9% across all patient subgroups. 4, 6
Approximately 80-90% of ceftazidime and 85% of avibactam are excreted unchanged in urine, with renal clearance being the primary elimination pathway for both drugs. 2
Critical Safety Monitoring
Monitor vigilantly for neurotoxicity (seizures, encephalopathy, confusion), particularly if renal function deteriorates during therapy, as beta-lactam accumulation can occur rapidly. 1, 7
While ceftazidime has lower pro-convulsive activity than some other beta-lactams, the risk remains present and requires careful clinical surveillance throughout treatment. 1
Infection-Specific Considerations
For complicated intra-abdominal infections, add metronidazole 500 mg IV every 6-8 hours to provide anaerobic coverage, as ceftazidime-avibactam lacks activity against anaerobes. 3
Treatment duration varies by indication: 7-14 days for complicated UTI/pyelonephritis, 5-14 days for complicated intra-abdominal infections, and 7-14 days for hospital-acquired/ventilator-associated pneumonia. 3