From the Guidelines
Ceftazidime-avibactam dosing in patients with chronic kidney disease (CKD) should be adjusted based on creatinine clearance (CrCl) to minimize the risk of adverse effects, as recommended by recent guidelines 1.
Dosing Adjustments
The following adjustments are recommended:
- For patients with CrCl greater than 50 mL/min, the standard dose of 2.5 g (2 g ceftazidime plus 0.5 g avibactam) every 8 hours should be used.
- For CrCl between 31-50 mL/min, reduce to 1.25 g every 8 hours.
- For CrCl between 16-30 mL/min, give 0.94 g every 12 hours.
- For CrCl between 6-15 mL/min, administer 0.94 g every 24 hours.
- For patients on hemodialysis, give 0.94 g every 48 hours, with dosing after hemodialysis on dialysis days.
Rationale
These adjustments are necessary because both ceftazidime and avibactam are primarily eliminated by the kidneys, and reduced renal function leads to drug accumulation 1. Without proper dose adjustment, patients with CKD may experience increased adverse effects including neurotoxicity (seizures, encephalopathy) and other toxicities.
Key Considerations
- Regular monitoring of renal function is recommended during treatment, with dose adjustments made if significant changes in kidney function occur 1.
- The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines suggest that ceftazidime-avibactam can be used for the treatment of severe infections due to carbapenem-resistant Enterobacterales (CRE) if active in vitro 1.
- However, the primary concern in CKD patients is to adjust the dose according to renal function to ensure safety and efficacy.
From the FDA Drug Label
Ceftazidime is eliminated almost solely by the kidneys; its serum half-life is significantly prolonged in patients with impaired renal function The clearance of avibactam was significantly decreased in subjects with mild (CrCl greater than 50 to 80 mL/min, n = 6), moderate (CrCl 30 to less than or equal to 50 mL/min, n = 6), and severe (CrCl 30 mL/min or less, not requiring hemodialysis; n = 6) renal impairment compared to healthy subjects with normal renal function (CrCl greater than 80 mL/min, n = 6) following administration of a single 100-mg intravenous dose of avibactam. 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. Because the exposure of both ceftazidime and avibactam is highly dependent on renal function, monitor renal function (i.e., CrCl in adult patients and eGFR in pediatric patients) at least daily and adjust the dosage of AVYCAZ accordingly [see Dosage and Administration (2. 3)].
Ceftazidime/avibactam in CKD:
- Dose adjustment is necessary in patients with moderate and severe renal impairment and end-stage renal disease.
- Monitoring of renal function is recommended at least daily to adjust the dosage of AVYCAZ accordingly.
- Increased risk of adverse reactions may occur in patients with decreased renal function, particularly in elderly patients. 2
From the Research
Ceftazidime-Avibactam in CKD
- Ceftazidime-avibactam is a combination antibiotic used to treat various infections, including those caused by carbapenem-resistant Gram-negative bacteria.
- In patients with chronic kidney disease (CKD), the dosage of ceftazidime-avibactam may need to be adjusted to avoid toxicity and ensure effective treatment 3.
- A study published in 2024 found that renal dose adjustment of ceftazidime-avibactam was independently associated with higher mortality in patients with KPC-producing Klebsiella pneumoniae bloodstream infection 4.
- Another study published in 2019 suggested that deferred renal dose reduction of wide therapeutic index antibiotics, including ceftazidime-avibactam, could improve outcomes in patients with infectious diseases 5.
- A systematic review and meta-analysis published in 2023 found that renal dosing adjustments of ceftazidime-avibactam were associated with a higher risk of mortality in patients with carbapenem-resistant Gram-negative infections 6.
Dosage Adjustment in CKD
- The dosage of ceftazidime-avibactam should be adjusted based on the patient's renal function, with a goal of maintaining adequate drug exposure while minimizing the risk of toxicity 3, 6.
- A study published in 2021 found that patients with chronic kidney disease were more likely to receive targeted ceftazidime-avibactam therapy, while those on dialysis were less likely to receive ceftazidime-avibactam compared to colistin 7.
- The optimal dosage adjustment strategy for ceftazidime-avibactam in patients with CKD is not well established and may require further study 4, 5, 6.
Clinical Implications
- Clinicians should carefully consider the patient's renal function when prescribing ceftazidime-avibactam, and adjust the dosage accordingly to minimize the risk of toxicity and ensure effective treatment 4, 3, 6.
- Further research is needed to determine the optimal dosage adjustment strategy for ceftazidime-avibactam in patients with CKD, and to fully understand the clinical implications of renal dose adjustment on patient outcomes 5, 6.