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

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 investiga...

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Publicado en:Pediatric Nephrology Vol. 40; no. 2; pp. 513 - 522
Autores principales: Pavia, Kathryn, Girdwood, Sonya Tang, Paice, Kelli, Dong, Min, Mizuno, Tomoyuki, Tang, Peter, Mangeot, Colleen, Vinks, Alexander A., Kaplan, Jennifer
Formato: research tables/charts Journal Article
Publicado: Springer Nature Feb2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Feb2025
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00467-024-06477-4
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        atl: Acute kidney injury is associated with abnormal cefepime exposure among critically ill children and young adults.
      aug:
        au:
          Pavia, Kathryn
          Girdwood, Sonya Tang
          Paice, Kelli
          Dong, Min
          Mizuno, Tomoyuki
          Tang, Peter
          Mangeot, Colleen
          Vinks, Alexander A.
          Kaplan, Jennifer
        affil: https://ror.org/01hcyya48 Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
      sug:
        subj:
          Cefepime Hydrochloride Adverse Effects
          Cefepime Hydrochloride Adverse Effects
          Kidney Failure, Acute Complications
          Kidney Failure, Acute Drug Therapy
          Environmental Exposure Risk Factors
          Critical Illness
          Risk Assessment
          Human
          Retrospective Design
          Pediatric Care
          Cefepime Hydrochloride Pharmacokinetics
          Probability
          Drug Toxicity
          Descriptive Statistics
          Cefepime Hydrochloride Administration and Dosage
          Funding Source
          Child
          Adolescence
          Child, Preschool
          Child: 6-12 years
          Adolescent: 13-18 years
          Child, Preschool: 2-5 years
      ab: 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 (Cmin) 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 Cmin ≥ 30 mg/L. Patients with elevated Cmin 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 (AUC24h) and Cmin. 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.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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