What is the recommended dose of Ceftazidime (Ceftazidime)-Avibactam for patients with impaired renal function?

From the Guidelines

The recommended dose of Ceftazidime-Avibactam for patients with impaired renal function requires adjustment based on the patient's creatinine clearance (CrCl). For patients with CrCl between 31-50 mL/min, the dose should be reduced to 1.25 grams (1 gram ceftazidime plus 0.25 gram avibactam) every 8 hours. For those with CrCl between 16-30 mL/min, the dose should be further reduced to 0.94 grams (0.75 gram ceftazidime plus 0.19 gram avibactam) every 12 hours. Patients with CrCl between 6-15 mL/min should receive 0.94 grams every 24 hours. For patients on hemodialysis, a loading dose of 0.94 grams should be given, followed by 0.94 grams every 48 hours, with administration timed after hemodialysis on dialysis days. These adjustments are necessary because both ceftazidime and avibactam are primarily eliminated by the kidneys, and reduced renal function leads to drug accumulation. Without appropriate dose adjustments, patients with renal impairment may experience toxicity, including neurotoxicity manifesting as seizures, encephalopathy, or coma. Each dose should be administered as an intravenous infusion over 2 hours, as recommended by recent guidelines 1.

Key Considerations

• The dose adjustments are crucial to prevent drug accumulation and potential toxicity in patients with impaired renal function.
• The recommended dose for patients with normal renal function is not explicitly stated in the provided evidence, but the standard dose is typically 2.5 grams (2 grams ceftazidime plus 0.5 gram avibactam) every 8 hours 1.
• It is essential to monitor renal function and adjust the dose accordingly to ensure optimal treatment outcomes and minimize the risk of adverse effects.
• The use of ceftazidime-avibactam in combination with other antimicrobial agents may not provide additional benefits in terms of mortality and microbiological cure rates, as suggested by observational studies and meta-analyses 1.

Administration and Monitoring

• Each dose of ceftazidime-avibactam should be administered as an intravenous infusion over 2 hours.
• Patients with impaired renal function require close monitoring of renal function and potential signs of toxicity, such as seizures, encephalopathy, or coma.
• The treatment outcomes and potential adverse effects should be closely monitored, and the dose adjusted accordingly to ensure optimal treatment outcomes.

From the FDA Drug Label

Dosage adjustment of AVYCAZ is recommended in adult and pediatric patients 2 years and older with moderate and severe renal impairment and end-stage renal disease. Population PK models for ceftazidime and avibactam were used to conduct simulations for patients with impaired renal function. Simulations demonstrated that the recommended dose adjustments [see Dosage and Administration (2. 3)] provide comparable exposures of ceftazidime and avibactam in both adult and pediatric patients with moderate and severe renal impairment and end-stage renal disease to those in patients with normal renal function or mild renal impairment.

The recommended dose of Ceftazidime-Avibactam for patients with impaired renal function is adjusted based on the severity of renal impairment.

• Moderate renal impairment: dose adjustment is recommended.
• Severe renal impairment: dose adjustment is recommended.
• End-stage renal disease: dose adjustment is recommended. The exact dose adjustments are not specified in the provided text, but it is recommended to consult the Dosage and Administration section (2.3) for specific guidance 2.

From the Research

Ceftazidime-Avibactam Dosing for Impaired Renal Function

• The recommended dose of Ceftazidime-Avibactam for patients with impaired renal function is as follows:
  • For patients with creatinine clearance (CLCR) >50 ml/min, the recommended dosage regimen is 2,000 + 500 mg every 8 hours by 2-hour intravenous infusion 3.
  • For patients with CLCR ≤50 ml/min, modified dosage regimens are recommended 3.
• A study on steady-state Ceftazidime-Avibactam serum concentrations in a critically ill patient undergoing continuous venovenous hemodiafiltration (CVVHDF) suggested that a dose of 2.5 g infused over 2 hours every 8 hours may be appropriate for patients with pneumonia receiving CVVHDF 4.
• Another study using PK/PD simulation found that the current recommended dosing regimen of Ceftazidime-Avibactam may be insufficient for severe infection patients, and continuous infusion is suggested 5.

Special Considerations

• For patients with augmented renal clearance, extended infusion durations may be necessary to achieve optimal PK/PD targets 5.
• The dosing regimen for Ceftazidime-Avibactam should be individualized based on the patient's renal function and the severity of the infection 3, 5.
• Higher doses may be necessary for patients with infections caused by Pseudomonas aeruginosa, due to limited ceftazidime penetration into epithelial lining fluid 4, 5.