From the Guidelines
The recommended dose of Ceftazidime-Avibactam for treating pneumonia in adults with normal renal function is 2.5 grams (2 grams ceftazidime plus 0.5 grams avibactam) administered intravenously every 8 hours. This dose is based on the most recent and highest quality study available, which provides guidelines for the treatment of infections due to multidrug-resistant organisms 1. The typical treatment duration for hospital-acquired or ventilator-associated pneumonia is 7 to 14 days, with the exact length depending on the severity of infection and clinical response.
Key Considerations
- The medication should be administered with consistent timing to maintain appropriate blood levels.
- Dosage adjustments are not needed for patients with normal renal function (creatinine clearance > 50 mL/min), but would be required for those with renal impairment.
- Ceftazidime-Avibactam works by combining a third-generation cephalosporin (ceftazidime) that disrupts bacterial cell wall synthesis with a beta-lactamase inhibitor (avibactam) that prevents bacterial enzymes from breaking down the antibiotic.
- This combination is particularly effective against multi-drug resistant gram-negative bacteria, including those producing extended-spectrum beta-lactamases and certain carbapenemases, making it an important option for serious pneumonia infections.
Clinical Context
The choice of Ceftazidime-Avibactam for pneumonia treatment should be guided by the severity of the infection, the susceptibility of the causative organism, and the patient's renal function. As noted in the guidelines for the treatment of infections due to multidrug-resistant organisms 1, the treatment duration and dosage may need to be adjusted based on individual patient factors.
Evidence Summary
The recommended dose of 2.5 grams every 8 hours is supported by recent guidelines 1, which emphasize the importance of appropriate antibiotic therapy for hospital-acquired and ventilator-associated pneumonia. While other studies, such as those from 2016 1, provide additional context for the treatment of pneumonia, the most recent guidelines should be prioritized for clinical decision-making.
From the Research
Ceftazidime-Avibactam Dosing for Pneumonia
- The recommended dose of Ceftazidime-Avibactam for pneumonia treatment in adults with normal renal function is 2,000 mg + 500 mg every 8 hours by 2-hour intravenous infusion 2.
- This dosage regimen was developed and validated using pharmacokinetic/pharmacodynamic (PK/PD) targets, population PK modeling, and probability of target attainment (PTA) analyses 2.
- The dosage regimen is robust, with high target attainment (>95%) against MICs ≤8 mg/liter achieved regardless of older age, obesity, augmented renal clearance, or severity of infection 2.
Clinical Efficacy
- Ceftazidime-Avibactam was non-inferior to meropenem in the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, in a randomized, double-blind, phase 3 non-inferiority trial 3.
- The clinical cure rate was 68.8% in the Ceftazidime-Avibactam group and 73.0% in the meropenem group, with a difference of -4.2% (95% CI -10.8 to 2.5) 3.
Renal Impairment
- Avibactam is primarily excreted unchanged in the urine, and renal impairment may affect its pharmacokinetics 4.
- The pharmacokinetics of Avibactam are affected by renal impairment, with decreasing clearance and increasing exposure and terminal half-life with increasing severity of renal impairment 4.
- Dose adjustment is warranted in patients with renal impairment, with a recommended dose reduction based on the severity of impairment 4, 5.
PK/PD Simulations
- Recent studies suggest that the current dosing regimen of Ceftazidime-Avibactam may be insufficient for severe infection patients, and continuous infusion may be necessary to achieve higher PK/PD targets 6.
- Monte Carlo simulations showed that the recommended dosage regimen could achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ CT=1.0 mg/L (avibactam), but may not be sufficient for severe infections 6.