Impact of Early Dose Adjustment of Piperacillin/Tazobactam on Mortality in Critically Ill Patients With Acute Kidney Injury: A Retrospective Multicenter Cohort Study

Abstract

Background:

Acute kidney injury (AKI) is common in critically ill patients, but the optimal dosing of beta-lactam antibiotics in this setting remains controversial. It is not known whether the benefit of initiating beta-lactams at normal doses outweighs the risk of accumulation and toxicity.

Objective:

We aimed to evaluate the association between early dose adjustment of piperacillin/tazobactam (PT) and 28-day intensive care unit (ICU) mortality in critically ill patients with AKI.

Methods:

We conducted a retrospective multicenter cohort study using the eICU Collaborative Research Database v2.0 and included adult ICU patients with AKI who received PT and had a pretreatment serum creatinine level corresponding to an estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m². The exposure was PT dose in the first 24 hours, which was categorized as normal (≥13.5 g/24 h) or adjusted (<13.5 g/24 h). The primary outcome was 28-day ICU mortality.

Results:

Among 1639 eligible patients, 224 (13.7%) received normal-dose PT and 1415 (86.3%) received adjusted doses. The overall 28-day ICU mortality was 11%, with significantly lower mortality in the normal-dose group (6.7%) compared with the adjusted-dose group (11.7%) (unadjusted odds ratio [OR] 1.85, 95% confidence interval [CI] 1.07-3.20; P = .028). After multivariable adjustment, early dose adjustment was independently associated with higher 28-day ICU mortality (adjusted OR 2.11, 95% CI 1.13-3.96; P = .020). Results were consistent across multiple subgroup and sensitivity analyses, but statistical significance was attenuated when the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used for eGFR estimation.

Conclusion and Relevance:

Early dose adjustment of PT in critically ill patients with AKI is associated with increased 28-day ICU mortality. This finding suggests that renal dose adjustment of PT should be deferred beyond the first 24 hours of therapy in this population. Prospective studies are needed to confirm this finding, define the optimal timing of subsequent dose adjustments, and assess safety outcomes.