From the Guidelines
For patients with normal renal function, the recommended dose of Ceftazidime-Avibactam is 2.5 grams (2 grams ceftazidime plus 0.5 grams avibactam) administered intravenously every 8 hours. This dosing regimen is based on the most recent and highest quality study available, which provides recommendations for the treatment of infections due to multidrug-resistant organisms 1. The study suggests that Ceftazidime-Avibactam is an effective treatment option for various infections, including those caused by carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales.
Key Considerations
- The dose of 2.5 grams every 8 hours is recommended for patients with normal renal function, as stated in the study 1.
- The typical duration of therapy depends on the type and severity of infection being treated, generally ranging from 5 to 14 days 1.
- When administering Ceftazidime-Avibactam, ensure proper dilution in an appropriate intravenous solution such as 0.9% sodium chloride or 5% dextrose.
- Monitor renal function during therapy as nephrotoxicity can occur, and be alert for potential adverse effects including hypersensitivity reactions and Clostridioides difficile-associated diarrhea.
Administration and Monitoring
- Each dose should be infused over 2 hours to maintain effective plasma concentrations of both components.
- Dose adjustments are necessary for patients with renal impairment, but not required for hepatic impairment.
- The study provides recommendations for various infections, including bloodstream infections, complicated urinary tract infections, and complicated intra-abdominal infections 1.
Evidence-Based Recommendation
The recommended dose of Ceftazidime-Avibactam is based on the highest quality evidence available, which suggests that this dosing regimen is effective in treating various infections caused by multidrug-resistant organisms 1.
From the FDA Drug Label
The mean pharmacokinetic parameters for ceftazidime and avibactam in healthy adult male subjects with normal renal function after single and multiple 2-hour intravenous infusions of AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered every 8 hours are summarized in Table 14.
The recommended dose of Ceftazidime-Avibactam for a patient with normal renal function is 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered every 8 hours as a 2-hour infusion 2.
- Dose: 2.5 grams
- Ceftazidime dose: 2 grams
- Avibactam dose: 0.5 grams
- Administration: 2-hour infusion
- Frequency: every 8 hours
From the Research
Ceftazidime-Avibactam Dosing for Normal Renal Function
- The recommended dose of Ceftazidime-Avibactam for patients with normal renal function is 2 grams of ceftazidime and 0.5 grams of avibactam administered every 8 hours as a 2-hour intravenous infusion 3, 4.
- This dosing regimen is supported by population pharmacokinetic models and Monte Carlo simulations, which demonstrated that it achieves sufficient joint probability of target attainment for ceftazidime minimum inhibitory concentration (MIC) of 8 mg/L at a fixed 4 mg/L avibactam concentration 3.
- The clinical efficacy of this dosing regimen has been demonstrated in phase III non-inferiority trials with carbapenem comparators for the treatment of complicated intra-abdominal infection, complicated urinary tract infection, and nosocomial pneumonia, including ventilator-associated pneumonia 3, 5, 4, 6.
Rationale for Dosing Regimen
- The dosing regimen is based on the pharmacokinetic profiles of ceftazidime and avibactam, which have a half-life of approximately 2 hours and are primarily eliminated by renal clearance 3, 7.
- The fixed-dose combination ratio of 4:1 (ceftazidime:avibactam) was selected to achieve optimal pharmacodynamic activity against Gram-negative pathogens 3.
- The dosing regimen has been validated using probability of target attainment simulations and has been shown to be robust across different patient populations, including those with older age, obesity, and augmented renal clearance 4.