What is the recommended Zosyn (piperacillin/tazobactam) dosage for a patient with an eGFR < 28 and creatinine level of 1.8?

Zosyn (Piperacillin/Tazobactam) Dosing for Patients with eGFR < 28 and Creatinine 1.8

For patients with eGFR < 28 mL/min and creatinine of 1.8, the recommended Zosyn dosage is 2.25 g every 8 hours administered by intravenous infusion over 30 minutes. 1

Dosage Recommendations Based on Renal Function

The FDA-approved dosing guidelines for Zosyn (piperacillin/tazobactam) in patients with renal impairment are as follows:

• For patients with creatinine clearance 20-40 mL/min:

  • Standard indications: 2.25 g every 6 hours 1
  • Nosocomial pneumonia: 3.375 g every 6 hours 1

• For patients with creatinine clearance <20 mL/min (which applies to this patient with eGFR <28):

  • Standard indications: 2.25 g every 8 hours 1
  • Nosocomial pneumonia: 2.25 g every 6 hours 1

Rationale for Dosage Adjustment

• Piperacillin and tazobactam are primarily eliminated by the kidneys, with decreased renal function leading to increased drug exposure 2
• Total body clearance, area under the curve, and terminal elimination rate of both piperacillin and tazobactam correlate with renal function 2
• Studies show that standard doses of piperacillin/tazobactam in patients with impaired renal function can lead to drug accumulation and potential toxicity 3

Clinical Considerations

• Higher doses of piperacillin/tazobactam (4.5 g) have been associated with increased risk of acute kidney injury in patients with pre-existing renal impairment, with rates of 25-38.5% compared to 0-5.6% with lower doses (2.25 g) 3
• Plasma concentrations of piperacillin/tazobactam can vary >10-fold between patients, even among those with similar renal function 4
• For patients with eGFR <28, the risk of drug accumulation and toxicity is significant, making appropriate dose adjustment crucial 2

Important Monitoring Parameters

• Regular monitoring of renal function is essential during treatment 3
• Signs of worsening renal function should prompt consideration of dose reduction or discontinuation 1
• Therapeutic drug monitoring may be beneficial in critically ill patients with renal impairment to ensure adequate drug exposure while avoiding toxicity 5

Potential Pitfalls

• Using standard doses in patients with renal impairment can lead to drug accumulation and nephrotoxicity 3
• Underdosing may result in subtherapeutic concentrations and treatment failure, particularly for resistant organisms 4
• The relationship between renal function and drug clearance is not perfectly linear, and significant variability exists between patients 4

Special Considerations

• For patients on hemodialysis, an additional dose of 0.75 g should be administered following each dialysis session 1
• For patients with fluctuating renal function, more frequent monitoring and dose adjustments may be necessary 1
• In critically ill patients with severe infections, the balance between achieving adequate antimicrobial concentrations and avoiding toxicity is particularly challenging 5