Acute kidney injury is associated with abnormal cefepime exposure among critically ill children and young adults.

Abstract

Background: Elevated cefepime blood concentrations can cause neurotoxicity in adults. The consequences of elevated cefepime concentrations among pediatric patients are unknown. Future exploration of such effects requires first identifying patients at risk for elevated cefepime exposure. We investigated the role of acute kidney injury as a risk factor for increased cefepime concentrations in critically ill children.

Methods: This was a retrospective analysis at a single pediatric intensive care unit. Analyzed patients received at least 24 h of cefepime and had at least two opportunistic samples collected for total cefepime concentration measurement. Individual pharmacokinetic (PK) profiles during treatment courses were reconstructed using Bayesian estimation with an established population PK model. Elevated trough concentration (C_min) was defined as ≥ 30 mg/L based on adult toxicity studies. The effect of kidney dysfunction on cefepime PK profiles was interrogated using a mixed-effect model.

Results: Eighty-seven patients were included, of which 13 (14.9%) had at least one estimated C_min ≥ 30 mg/L. Patients with elevated C_min were more likely to have acute kidney injury (AKI) during their critical illness (92% vs. 57%, p = 0.015 for any AKI; 62% vs. 26%, p = 0.019 for severe AKI). Patients who had AKI during critical illness had significantly higher cefepime exposure, as quantified by the area under the concentration-time curve over 24 h (AUC_24h) and C_min.

Conclusions: Among critically ill children, AKI is associated with elevated cefepime concentrations. Identifying these high-risk patients is the first step toward evaluating the clinical consequences of such exposures.