What is the recommended dosage of Zosyn (piperacillin/tazobactam) for patients with impaired renal function?

Zosyn (Piperacillin/Tazobactam) Dosing in Renal Impairment

For patients with renal impairment, Zosyn (piperacillin/tazobactam) dosage should be adjusted based on creatinine clearance, with 2.25g every 6 hours for CrCl 20-40 mL/min, 2.25g every 8 hours for CrCl <20 mL/min, and 2.25g every 12 hours for hemodialysis patients with an additional 0.75g dose after each dialysis session. 1

Dosing Recommendations Based on Renal Function

Normal Renal Function (CrCl >40 mL/min)

• Standard dosing: 3.375g IV every 6 hours for most infections 1
• For nosocomial pneumonia: 4.5g IV every 6 hours 1

Moderate Renal Impairment (CrCl 20-40 mL/min)

• 2.25g IV every 6 hours for most infections 1
• 3.375g IV every 6 hours for nosocomial pneumonia 1

Severe Renal Impairment (CrCl <20 mL/min)

• 2.25g IV every 8 hours for most infections 1
• 2.25g IV every 6 hours for nosocomial pneumonia 1

Hemodialysis Patients

• 2.25g IV every 12 hours for most infections 1
• 2.25g IV every 8 hours for nosocomial pneumonia 1
• An additional dose of 0.75g should be administered following each dialysis session on hemodialysis days 1

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• 2.25g IV every 12 hours for most infections 1
• 2.25g IV every 8 hours for nosocomial pneumonia 1
• No additional dosage is necessary for CAPD patients 1

Administration Considerations

• Administer by intravenous infusion over 30 minutes 1
• For hemodialysis patients, administer the dose after hemodialysis to avoid premature removal of the drug 1
• Hemodialysis removes approximately 30% to 40% of the administered dose, necessitating the supplemental dose 1

Clinical Considerations and Evidence

• Recent evidence suggests that underdosing piperacillin/tazobactam in critically ill patients, particularly those with septic shock, is associated with worse clinical outcomes including higher mortality 2
• Extended or prolonged infusions of piperacillin/tazobactam may provide better pharmacodynamic target attainment in patients with varying degrees of renal function 3
• For patients with CrCl 41-120 mL/min, prolonged infusions (3-4 hours) of either 4.5g or 3.375g every 6 hours achieved ≥95% probability of target attainment versus ≥76% for standard 30-minute infusions 3

Common Pitfalls to Avoid

• Failing to adjust the dose based on the specific indication (e.g., nosocomial pneumonia requires higher dosing) 1
• Not administering the supplemental dose after hemodialysis, which can lead to subtherapeutic drug levels 1
• Excessive dose reduction in patients with renal impairment who have severe infections, which may lead to treatment failure 2
• Not considering the use of prolonged infusions in critically ill patients with serious infections, which may improve pharmacodynamic target attainment 3

Special Considerations

• Pharmacokinetic studies suggest that patients undergoing continuous renal replacement therapy (CRRT) may require individualized dosing based on residual renal function and the specific CRRT modality used 4
• For patients with fluctuating renal function, more frequent monitoring of renal function may be necessary to guide appropriate dosing adjustments 1