What is the relationship between Piperacillin (Pip/Taz) (Piperacillin/Tazobactam) and Acute Kidney Injury (AKI)?

From the Guidelines

Piperacillin/Tazobactam (Pip/Taz) is associated with an increased risk of Acute Kidney Injury (AKI), particularly in critically ill patients undergoing renal replacement therapy (RRT), and therapeutic drug monitoring (TDM) is recommended to optimize treatment and minimize this risk. The relationship between Piperacillin/Tazobactam and AKI is complex, and several factors contribute to the increased risk of kidney injury, including the type of RRT technique used, dialysis flow rates, and the patient's residual renal function 1.

Key Considerations

• The incidence of AKI in ICU patients is approximately 40%, with about 20% requiring RRT 1.
• RRT can significantly alter the pharmacokinetics of beta-lactam antibiotics, including Piperacillin/Tazobactam, making it challenging to achieve optimal dosing 1.
• The elimination rate of Piperacillin and Tazobactam varies depending on the RRT technique, with CVVHDF resulting in shorter half-lives compared to CVVH 1.
• Personalized TDM is necessary to ensure optimal beta-lactam dosing in patients undergoing RRT, as general recommendations are difficult to propose due to the variability in patient factors and RRT techniques 1.

Clinical Implications

• Clinicians should be aware of the potential increased risk of AKI when using Piperacillin/Tazobactam, particularly in critically ill patients undergoing RRT.
• Regular monitoring of renal function and adjustment of antibiotic dosing based on TDM results can help minimize the risk of AKI.
• Consideration of alternative antibiotics and avoidance of other nephrotoxic agents may be necessary in patients at high risk of AKI.

From the FDA Drug Label

The use of piperacillin and tazobactam 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 [see Adverse Reactions (6. 1)]. Combined use of piperacillin and tazobactam and vancomycin may be associated with an increased incidence of acute kidney injury [see Drug Interactions (7.3)].

Piperacillin/Tazobactam may increase the risk of Acute Kidney Injury (AKI), especially in critically ill patients and when combined with vancomycin.

• Key points:
  • Piperacillin/Tazobactam is an independent risk factor for renal failure.
  • Delayed recovery of renal function is associated with Piperacillin/Tazobactam use.
  • Combined use with vancomycin may increase the incidence of AKI. 2 2 2

From the Research

Relationship between Piperacillin/Tazobactam and Acute Kidney Injury

The relationship between Piperacillin/Tazobactam (Pip/Taz) and Acute Kidney Injury (AKI) has been investigated in several studies.

• A study published in 2023 3 found that the risk of AKI was highly associated with vancomycin trough concentration above 20 mcg/mL, nephrotoxic medications, and African descent, but the difference in AKI risk between Pip/Taz and other broad-spectrum antibiotics was not statistically significant.
• Another study from 2017 4 compared the risk of AKI with vancomycin plus Pip/Taz versus vancomycin plus cefepime and found that Pip/Taz was associated with a higher risk of AKI, particularly in patients with normal baseline renal function.
• A multicenter propensity score-matched study from 2022 5 found that concomitant vancomycin and Pip/Taz administration in adult ICU patients was independently associated with an increased risk of AKI.
• A single-center retrospective cohort study from 2019 6 found that the incidence of AKI in patients treated with Pip/Taz was higher than that in patients treated with cefepime, and Pip/Taz was an independent risk factor of AKI.
• A retrospective multicentre cohort study from 2024 7 found that exposure to Pip/Taz was associated with increased risk of AKI and renal replacement therapy, regardless of combination therapy with vancomycin.

Key Findings

• Pip/Taz is associated with an increased risk of AKI, particularly when combined with vancomycin 4, 5, 7.
• The risk of AKI is higher in patients with normal baseline renal function 4.
• Pip/Taz is an independent risk factor of AKI 5, 6.
• The incidence of AKI is higher in patients treated with Pip/Taz than in patients treated with cefepime 6.
• Exposure to Pip/Taz is associated with increased risk of renal replacement therapy 7.