Can Zosyn (Piperacillin/Tazobactam) cause Acute Kidney Injury (AKI)?

From the Guidelines

Yes, Zosyn (piperacillin-tazobactam) can cause acute kidney injury (AKI). Although the provided evidence does not directly address the relationship between Zosyn and AKI, it does mention the potential for nephrotoxicity with certain antibiotics, such as aminoglycosides, and the importance of caution in patients with renal failure or those at risk of acute kidney injury 1. The guideline highlights the need for careful consideration when using antibiotics that may have nephrotoxic effects, particularly in vulnerable populations.

When considering the use of Zosyn, it is essential to be aware of the potential risks of AKI, especially in patients with pre-existing kidney disease, older age, dehydration, or those taking other nephrotoxic medications. The mechanism of AKI associated with Zosyn is thought to involve acute interstitial nephritis, where the drug triggers an immune-mediated inflammatory response in the kidney tissue.

Key considerations for minimizing the risk of AKI when using Zosyn include:

• Monitoring kidney function through regular serum creatinine measurements
• Maintaining adequate hydration
• Adjusting dosing based on renal function
• Being cautious when combining Zosyn with other nephrotoxic agents, such as vancomycin
• Considering alternative antibiotics with lower nephrotoxic potential if clinically appropriate.

It is crucial to weigh the benefits of using Zosyn against the potential risks, particularly in patients at high risk of AKI, and to closely monitor patients for signs of kidney injury during treatment 1.

From the FDA Drug Label

• Nephrotoxicity in critically ill patients has been observed; the use of ZOSYN was found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs in a randomized, multicenter, controlled trial in critically ill patients • Co-administration of ZOSYN with vancomycin may increase the incidence of acute kidney injury. Monitor kidney function in patients receiving ZOSYN and vancomycin. (7.3)

Zosyn and Acute Kidney Injury (AKI):

• Zosyn may cause nephrotoxicity, which can lead to renal failure and delayed recovery of renal function in critically ill patients.
• Co-administration of Zosyn with vancomycin may increase the incidence of acute kidney injury (AKI).
• Patients with renal impairment should have their dosage reduced based on the degree of renal impairment.
• It is recommended to monitor renal function during treatment with Zosyn, especially in critically ill patients or those receiving Zosyn and vancomycin 2.

From the Research

Zosyn and Acute Kidney Injury (AKI)

• Zosyn, also known as piperacillin-tazobactam, is a combination antibiotic used to treat various infections, including those caused by gram-negative bacteria.
• The association between Zosyn and AKI has been investigated in several studies:
  • A systematic review and meta-analysis published in 2022 3 found that the combination of Zosyn and vancomycin was associated with a higher risk of AKI compared to alternative antibiotic regimens.
  • A retrospective observational study published in 2017 4 found that higher doses of Zosyn were associated with a higher frequency of AKI in patients with impaired renal function.
  • A cohort study published in 2017 5 found that the combination of Zosyn and vancomycin was associated with a higher risk of AKI compared to the combination of cefepime and vancomycin, particularly in patients with normal baseline renal function.
  • A retrospective cohort study published in 2020 6 found that the risk of AKI was similar between patients receiving Zosyn and vancomycin and those receiving cefepime and vancomycin.
  • Another retrospective cohort study published in 2020 7 found that the incidence of AKI in patients receiving continuous-infusion Zosyn and concomitant vancomycin was comparable to that found in previous studies using intermittent or extended-infusion Zosyn.

Risk Factors for AKI

• Several risk factors for AKI have been identified in patients receiving Zosyn, including:
  • Baseline renal impairment 4, 5, 7
  • Higher doses of Zosyn 4
  • Supratherapeutic vancomycin troughs 6
  • Duration of combination therapy 6
  • Severity of illness, including admission to the intensive care unit 7
  • Use of vasopressors 6

Comparison of Zosyn to Alternative Antibiotics

• The combination of Zosyn and vancomycin has been compared to alternative antibiotic regimens, including:
  • Cefepime and vancomycin 3, 5, 6
  • Alternative gram-negative coverage antibiotics 3
• The results of these comparisons suggest that Zosyn may be associated with a higher risk of AKI compared to some alternative antibiotics, particularly in patients with normal baseline renal function.