From the Guidelines
Zosyn (piperacillin/tazobactam) dose adjustment is crucial in patients with impaired renal function to prevent toxicity and ensure therapeutic efficacy. The dose adjustment protocol for Zosyn in patients with impaired renal function is as follows:
- For patients with creatinine clearance (CrCl) greater than 40 mL/min, the standard dose of 3.375 g every 6 hours or 4.5 g every 6 hours can be used 1.
- For patients with CrCl between 20-40 mL/min, the dose should be reduced to 2.25 g every 6 hours.
- When CrCl is less than 20 mL/min, the dose should be further reduced to 2.25 g every 8 hours.
- For patients on hemodialysis, 2.25 g every 8 hours is recommended with an additional dose of 0.75 g after each dialysis session.
It is essential to note that piperacillin and tazobactam are primarily eliminated by the kidneys, and reduced renal function leads to drug accumulation 1. Without proper dose adjustment, patients with renal impairment may experience increased adverse effects, including neurotoxicity, seizures, and electrolyte disturbances. Regular monitoring of renal function during therapy is necessary, as changes may necessitate further dose adjustments. The goal is to maintain therapeutic efficacy while minimizing toxicity in patients with compromised kidney function. In critically ill patients, including those with sepsis and septic shock, optimizing antimicrobial dosing strategies is crucial to improve outcomes 1. Extended or continuous infusion of β-lactams, such as piperacillin/tazobactam, may be more effective than intermittent rapid infusion, particularly for relatively resistant organisms and in critically ill patients with sepsis 1.
From the FDA Drug Label
2.4 Dosage in Adult Patients with Renal Impairment In adult patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced based on the degree of renal impairment The recommended daily dosage of piperacillin and tazobactam for injection for patients with renal impairment administered by intravenous infusion over 30 minutes is described in Table 1 Table 1: Recommended Dosage of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam)
Administer piperacillin and tazobactam for injection by intravenous infusion over 30 minutes.
- Creatinine clearance for patients not receiving hemodialysis ** 0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days Creatinine clearance, mL/min | All Indications (except nosocomial pneumonia) | Nosocomial Pneumonia Greater than 40 mL/min | 3.375 every 6 hours | 4.5 every 6 hours 20 to 40 mL/min* | 2.25 every 6 hours | 3.375 every 6 hours Less than 20 mL/min* | 2.25 every 8 hours | 2.25 every 6 hours Hemodialysis** | 2.25 every 12 hours | 2.25 every 8 hours CAPD | 2.25 every 12 hours | 2.25 every 8 hours
The Zosyn dose adjustment protocol for patients with impaired renal function is as follows:
- For patients with creatinine clearance greater than 40 mL/min, the recommended dose is 3.375 g every 6 hours for all indications except nosocomial pneumonia, and 4.5 g every 6 hours for nosocomial pneumonia.
- For patients with creatinine clearance between 20-40 mL/min, the recommended dose is 2.25 g every 6 hours for all indications except nosocomial pneumonia, and 3.375 g every 6 hours for nosocomial pneumonia.
- For patients with creatinine clearance less than 20 mL/min, the recommended dose is 2.25 g every 8 hours for all indications except nosocomial pneumonia, and 2.25 g every 6 hours for nosocomial pneumonia.
- For patients on hemodialysis, the recommended dose is 2.25 g every 12 hours for all indications except nosocomial pneumonia, and 2.25 g every 8 hours for nosocomial pneumonia, with an additional dose of 0.75 g administered after each dialysis session.
- For patients on CAPD, the recommended dose is 2.25 g every 12 hours for all indications except nosocomial pneumonia, and 2.25 g every 8 hours for nosocomial pneumonia 2
From the Research
Zosyn Renal Dose Protocol
The Zosyn (piperacillin/tazobactam) dose adjustment protocol for patients with impaired renal function is as follows:
- Dosage alterations are recommended for creatinine clearance values less than 40 ml/min 3
- For patients with creatinine clearance between 20-40 mL/min, prolonged infusions of 4.5 g every 8 hours achieved slightly higher probability of target attainment (PTA) compared to standard regimens 4
- In patients with creatinine clearance between 1-19 mL/min, PTA achieved with prolonged infusions of 4.5 g every 12 hours was comparable to standard regimens 4
- A dose of 12/1.5 g/24 h as a continuous infusion is sufficient to reach a tazobactam concentration above the target and a piperacillin concentration above the target of 100% fT>1×MIC (minimum inhibitory concentration [MIC] ≤ 16 mg/L) 5
Dosing Considerations
- The pharmacokinetics of piperacillin and tazobactam correlate with renal function, and dosage adjustments should be made accordingly 3, 6
- Higher doses of piperacillin/tazobactam may be associated with a decline in renal function, even if the dose frequency is reduced 7
- Dosing regimens should be individualized based on renal function, MIC, and therapeutic drug monitoring to enhance target attainment 5
Renal Function Categories
- For patients with normal renal function (creatinine clearance > 120 mL/min), standard dosing regimens can be used 4
- For patients with moderate renal impairment (creatinine clearance 41-120 mL/min), prolonged infusions of 4.5 g every 6 hours can be used 4
- For patients with severe renal impairment (creatinine clearance 20-40 mL/min), prolonged infusions of 4.5 g every 8 hours can be used 4
- For patients with end-stage renal disease (creatinine clearance < 20 mL/min), dosing regimens should be individualized based on residual renal function and MIC 6