Research Horizons


Improved Piperacillin Dosing May Lower Risk of AKI in Critically Ill Patients

Hospital Medicine | Top Scientific Achievement
2023 Research Discoveries

Precision dosing for antibiotics like piperacillin/tazobactam in critically ill children may help lower the risk of adverse effects, including acute kidney injury (AKI). That’s because total piperacillin/tazobactam exposure early in each patient’s course of treatment is linked with a higher risk of AKI development.

A recent study led by first and corresponding author Sonya Tang Girdwood, MD, PhD, and senior author Stuart Goldstein, MD, sheds light on the link between this commonly used antibiotic combination and AKI.

Piperacillin/tazobactam is frequently used to treat critically ill children with systemic infections. While there is a known association between piperacillin/tazobactam and AKI, the exact relationship between piperacillin concentrations and AKI remains unclear.

This study estimated piperacillin/tazobactam exposures in 107 critically ill children and young adults to identify concentrations and clinical factors associated with AKI. Specifically, the team measured piperacillin area under the curve (AUC), highest peak and highest trough after administration. They then evaluated AKI after dosing, as defined by “Kidney Disease: Improving Global Outcomes Stage 2/3.” Finally, the team performed a regression analysis to identify patient and clinical predictors of piperacillin-associated AKI.

Researchers demonstrated a relationship between the estimated highest trough in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI.

“Beta-lactam antibiotics have long been thought to be very safe, but there is emerging evidence that some of them may cause toxicity. This is especially true in critically ill patients with kidney dysfunction since the antibiotics are cleared by the kidney,” Tang Girdwood says.

Next steps for this research include understanding the mechanisms connecting piperacillin/tazobactam and AKI, as well as studying the relationship between the antibiotics and non-creatinine AKI biomarkers. Ultimately, the researchers seek to develop model-informed precision antibiotic dosing to reduce antibiotic-associated AKI incidence in critically ill patients.

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Publication Information
Original title: Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury
Published in: Journal of Antimicrobial Chemotherapy
Publish date: Feb. 1, 2023
Read the study

Research By

Stuart Goldstein, MD
Stuart Goldstein, MD
Director, Center for Acute Care Nephrology

My research is focused on short- and long-term outcomes for children who have AKI and those who are at risk for AKI.