What are the recommended dosing regimens of ceftazidime‑tazobactam for different infections in adults, including adjustments for renal impairment, and the weight‑based dosing for pediatric patients?

Ceftazidime-Tazobactam Dosing by Infection Type

Standard Adult Dosing Regimens

For complicated intra-abdominal infections and complicated urinary tract infections in adults with normal renal function, administer ceftazidime-tazobactam 1.5 g (ceftazidime 1 g/tazobactam 0.5 g) intravenously every 8 hours as a 1-hour infusion. 1

Dosing by Infection Severity and Type

• Complicated intra-abdominal infections (cIAI): 1.5 g IV every 8 hours over 1 hour 1
• Complicated urinary tract infections (cUTI): 1.5 g IV every 8 hours over 1 hour 1
• Pseudomonas aeruginosa bacteremia: Standard 1 g dose achieves adequate pharmacodynamic targets (fT >40% MIC) in over 90% of cases, but for severe infections requiring fT >100% MIC, escalate to 2 g every 8 hours with extended 3-hour infusion 2

Optimized Infusion Strategies for Severe Infections

For severe infections in patients with normal or augmented renal clearance, extend the infusion duration to 3-4 hours rather than the standard 1-hour infusion to achieve higher pharmacodynamic targets. 3

• Patients with creatinine clearance >90 mL/min and severe infections benefit from 3-hour infusions to reach fT >100% MIC for ceftazidime 3
• Extended infusions (3-4 hours) are particularly important when treating Pseudomonas aeruginosa with higher MIC values or when beta-lactamase expression is elevated 2
• Continuous infusion may be considered for critically ill patients requiring 100% fT ≥ 4×MIC, though this requires higher dosages 3

Renal Impairment Dosing Adjustments

Dosage adjustments are mandatory for moderate-to-severe renal impairment, as ceftazidime is predominantly excreted unchanged in urine (≥92%). 1

Specific Renal Adjustment Regimens

• Creatinine clearance 30-50 mL/min: Reduce to 750 mg (ceftazidime 500 mg/tazobactam 250 mg) every 8 hours 1
• Creatinine clearance 15-29 mL/min: Reduce to 375 mg (ceftazidime 250 mg/tazobactam 125 mg) every 8 hours 1
• Creatinine clearance <15 mL/min: Administer loading dose followed by maintenance dosing every 24-48 hours 1
• Hemodialysis patients: Administer supplementary dose after each dialysis session 4
• Continuous peritoneal dialysis: Loading dose of 10 mg/kg followed by 5 mg/kg into each dialysis cavity 4

Alternative Simplified Renal Dosing

• For patients with renal impairment, consider administering the full 1.5 g dose at extended intervals (every 12 or 24 hours) as a prolonged infusion rather than using fractional doses, which achieves similar pharmacodynamic targets while reducing dosing errors 5
• This approach is particularly practical as only one vial strength is commercially available 5

Pediatric Weight-Based Dosing

Pediatric dosing has not been established in published guidelines for ceftazidime-tazobactam specifically, as this combination is primarily studied and approved for adult populations. 1

• For ceftazidime monotherapy in children, the traditional dose is 30-50 mg/kg every 8 hours, with maximum doses not exceeding adult dosing 6
• Neonates and infants require individualized dosing based on postmenstrual age and renal maturation 6

Critical Pharmacodynamic Considerations

• Target pharmacodynamic parameter: Time above MIC (fT >MIC) of 40-50% for bactericidal activity against Enterobacteriaceae and Pseudomonas aeruginosa 1
• For severe infections, aim for fT >100% MIC, which requires dose escalation to 2 g every 8 hours with extended infusion 2, 3
• Ceftazidime demonstrates lower protein binding (20%) compared to other cephalosporins, facilitating tissue penetration 1
• Tazobactam requires fT >40-70% above threshold concentrations (1.0-4.0 mg/L) depending on beta-lactamase burden 2, 3

Duration of Therapy

• Complicated intra-abdominal infections: Limit antimicrobial therapy to 4-7 days when adequate source control is achieved 6
• Longer durations have not been associated with improved outcomes and should be reserved for cases where source control is difficult 6

Common Pitfalls and Caveats

• Augmented renal clearance: Critically ill patients with creatinine clearance >130 mL/min may require higher doses (2 g every 8 hours) or continuous infusion to maintain adequate drug exposure 2, 3
• High MIC Pseudomonas strains: Standard dosing may be inadequate for isolates with MIC ≥4 mg/L; consider extended infusion or alternative agents 2
• Regional resistance patterns: Pseudomonas aeruginosa susceptibility varies geographically, requiring local antibiogram review before empiric use 3
• Fractional dosing errors: Using partial vials for renal-adjusted doses increases preparation errors; full-dose extended-interval regimens are safer alternatives 5