What is the recommended ceftazidime‑avibactam dosing, including the avibactam component, for a complicated urinary tract infection caused by Klebsiella species, with dose adjustments for different levels of renal impairment?

Ceftazidime-Avibactam Dosing for Klebsiella Complicated UTI

For complicated urinary tract infections caused by Klebsiella species, the recommended dose is ceftazidime-avibactam 2.5 g (ceftazidime 2 g and avibactam 0.5 g) IV every 8 hours, infused over 2 hours, for a duration of 5-7 days. 1, 2

Standard Dosing for Normal Renal Function

• Patients with creatinine clearance (CrCl) >50 mL/min should receive the full dose of 2.5 g IV every 8 hours by 2-hour infusion. 2
• The avibactam component in this regimen is 0.5 grams, maintaining the 4:1 ratio of ceftazidime to avibactam that has been validated in clinical trials. 2, 3
• Treatment duration is 7-14 days, with 7 days appropriate for patients with prompt clinical response and 14 days for delayed response or when prostatitis cannot be excluded in males. 1, 4

Renal Dose Adjustments

Moderate Renal Impairment (CrCl 31-50 mL/min)

• Reduce to 1.25 g (ceftazidime 1 g and avibactam 0.25 g) IV every 8 hours by 2-hour infusion. 2
• This represents a 50% dose reduction while maintaining the same dosing interval. 2

Severe Renal Impairment (CrCl 16-30 mL/min)

• Reduce to 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) IV every 12 hours by 2-hour infusion. 2
• The dosing interval is extended to every 12 hours due to decreased renal clearance. 2

Very Severe Renal Impairment (CrCl 6-15 mL/min)

• Administer 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) IV every 24 hours by 2-hour infusion. 2
• Both ceftazidime and avibactam are hemodialyzable, so administer after hemodialysis on hemodialysis days. 2

End-Stage Renal Disease (CrCl ≤5 mL/min)

• Administer 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) IV every 48 hours by 2-hour infusion. 2
• More than 50% of administered avibactam is removed during a 4-hour hemodialysis session, necessitating post-dialysis administration. 5, 6

Critical Pharmacokinetic Considerations

• Avibactam is primarily excreted unchanged in the urine, making renal function the primary determinant of dosing adjustments. 5
• The linear relationship between avibactam clearance and creatinine clearance is similar to that of ceftazidime, supporting the maintained 4:1 ratio across all renal function categories. 5, 3
• Monitor creatinine clearance at least daily in patients with changing renal function and adjust dosing accordingly to prevent subtherapeutic exposures. 2, 7

Pharmacodynamic Targets

• The dosing regimen achieves >95% target attainment against MICs ≤8 mg/L for Klebsiella species, regardless of age, obesity, or augmented renal clearance. 3
• The pharmacodynamic targets are 50% free time above the MIC for ceftazidime and free time above 1 mg/L for avibactam. 3
• These targets are achieved simultaneously with the approved dosing regimens across all renal function categories. 3

Common Pitfalls to Avoid

• Do not use single-dose aminoglycoside therapy as a substitute for the full ceftazidime-avibactam course in complicated UTI; single-dose aminoglycosides are only appropriate for simple cystitis due to carbapenem-resistant Enterobacterales. 1, 4
• Avoid underdosing in patients with rapidly improving renal function, as the modified dosage adjustments (50% increase in total daily dose for moderate/severe impairment) were specifically designed to prevent subtherapeutic exposures. 7
• Do not forget to infuse over 2 hours—shorter infusion times may compromise pharmacodynamic target attainment. 2, 3
• For hemodialysis patients, always administer after dialysis to avoid removing the drug before it can exert its antimicrobial effect. 2, 5, 6