What is the recommended dose of ceftazidime (CAZ) - avibactam (AVI) in pediatric patients?

Recommended Dosage of Ceftazidime-Avibactam in Pediatric Patients

For pediatric patients, ceftazidime-avibactam should be dosed according to age: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) every 8 hours for children 6 months to <18 years; 50 mg/kg (ceftazidime 40 mg/kg and avibactam 10 mg/kg) every 8 hours for children 3 months to <6 months; and 37.5 mg/kg (ceftazidime 30 mg/kg and avibactam 7.5 mg/kg) every 8 hours for infants >28 days to <3 months, with a maximum dose of 2.5 grams per administration. 1

Age-Based Dosing Recommendations

The FDA-approved dosing for ceftazidime-avibactam in pediatric patients is stratified by age:

• 2 years to <18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) every 8 hours, maximum 2.5 grams per dose 1
• 6 months to <2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) every 8 hours 1
• 3 months to <6 months: 50 mg/kg (ceftazidime 40 mg/kg and avibactam 10 mg/kg) every 8 hours 1
• >28 days to <3 months: 37.5 mg/kg (ceftazidime 30 mg/kg and avibactam 7.5 mg/kg) every 8 hours 1
• ≤28 days (GA ≥31 weeks): 25 mg/kg (ceftazidime 20 mg/kg and avibactam 5 mg/kg) every 8 hours 1

Administration Guidelines

• All doses should be administered as an intravenous infusion over 2 hours 1
• Treatment duration depends on the indication:
  • Complicated intra-abdominal infections: 5-14 days 1
  • Complicated urinary tract infections: 7-14 days 1
  • Hospital-acquired/ventilator-associated bacterial pneumonia: 7-14 days 1

Renal Dosage Adjustments

For pediatric patients aged 2 years and older with renal impairment, dosage adjustments are necessary:

• eGFR 31-50 mL/min/1.73m²: 31.25 mg/kg (maximum 1.25 grams) every 8 hours 1
• eGFR 16-30 mL/min/1.73m²: 23.75 mg/kg (maximum 0.94 grams) every 12 hours 1

For patients with changing renal function, monitor eGFR at least daily and adjust dosage accordingly 1

Clinical Evidence Supporting Dosing

The recommended pediatric dosing regimens are supported by population pharmacokinetic modeling and probability of target attainment studies. The updated models supported the approval of the current dosage regimens for children ≥3 months with creatinine clearance >50 mL/min/1.73 m² 2.

Special Considerations

• For complicated intra-abdominal infections, ceftazidime-avibactam should be used in conjunction with metronidazole (10 mg/kg IV every 8 hours in pediatric patients) 1
• Limited data exists for use in extremely premature neonates, though case reports suggest that the standard pediatric dose (62.5 mg/kg every 8 hours) has been used successfully in some cases 3
• Safety and efficacy have been demonstrated in children ≥3 months with complicated intra-abdominal infections, with favorable clinical and microbiological responses in ≥90% of patients 4

Monitoring Recommendations

• Monitor for adverse events, which may include gastrointestinal symptoms, infusion site reactions, and potential neurological effects 4
• For patients with renal impairment, monitor renal function regularly and adjust dosing as needed 1
• Assess clinical response within 48-72 hours of initiating therapy 4

Common Pitfalls and Caveats

• Ensure appropriate weight-based dosing calculations to avoid under or overdosing 1
• Remember that both ceftazidime and avibactam are hemodialyzable; administer after hemodialysis on dialysis days 1
• Do not use in patients with known severe hypersensitivity to ceftazidime, avibactam, or other cephalosporins 1
• There is insufficient information to recommend a dosing regimen for pediatric patients less than 2 years of age with renal impairment 1

By following these age-appropriate dosing guidelines and considering renal function, clinicians can optimize the use of ceftazidime-avibactam in pediatric patients while minimizing the risk of adverse effects and promoting favorable clinical outcomes.