The Journal of antimicrobial chemotherapy · 2026
Identification and assessment of paediatric cefepime-induced neurotoxicity in a retrospective cohort of paediatric intensive care patients.
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Pavia Kathryn, Day Melissa E, Hambrick H Rhodes, Sibilia Anna, Fenchel Matthew, Paice Kelli, Kaplan Jennifer, Tang Girdwood Sonya
Аннотация
BACKGROUND AND OBJECTIVE: Cefepime-induced neurotoxicity (CIN) is a recognized side effect of excessive cefepime exposure and high plasma concentrations in adults. However, the relationship between cefepime concentrations and neurotoxic symptoms in paediatric patients is unknown. The objective of this paper is to explore the relationship between cefepime pharmacokinetics and CIN in a paediatric intensive care unit (PICU) cohort.
PATIENTS AND METHODS: PICU patients with cefepime concentrations measured for a previous PK study were chosen for this cohort. CIN symptoms and related testing were evaluated by retrospective chart review and likelihood of causal association was determined using blinded adjudicators via the Naranjo adverse drug reaction probability scale.
RESULTS: Among 73 patients with complete data, 43 patients (59%) had either no neurotoxicity or neurotoxicity doubtful to be CIN, while 25 (34%) patients had possible CIN and five (7%) had probable CIN. Symptoms of neurotoxicity included irritability, altered mental status, depressed level of consciousness, myoclonus, seizures and delirium. There were no differences in age, sex, severity of illness or renal dysfunction among groups. Patients with probable CIN had higher cefepime area under the curve (2250 versus 1107 mg*h/L, P = 0.03) and peak concentrations (232 versus 172 mg/L, P < 0.001).
CONCLUSIONS: This investigation presents a paediatric cohort analysis of CIN and provides preliminary evidence supporting the hypothesis that neurotoxicity risk is probably concentration dependent in this age group and presents with similar spectrum of symptoms as those described in adults.
PATIENTS AND METHODS: PICU patients with cefepime concentrations measured for a previous PK study were chosen for this cohort. CIN symptoms and related testing were evaluated by retrospective chart review and likelihood of causal association was determined using blinded adjudicators via the Naranjo adverse drug reaction probability scale.
RESULTS: Among 73 patients with complete data, 43 patients (59%) had either no neurotoxicity or neurotoxicity doubtful to be CIN, while 25 (34%) patients had possible CIN and five (7%) had probable CIN. Symptoms of neurotoxicity included irritability, altered mental status, depressed level of consciousness, myoclonus, seizures and delirium. There were no differences in age, sex, severity of illness or renal dysfunction among groups. Patients with probable CIN had higher cefepime area under the curve (2250 versus 1107 mg*h/L, P = 0.03) and peak concentrations (232 versus 172 mg/L, P < 0.001).
CONCLUSIONS: This investigation presents a paediatric cohort analysis of CIN and provides preliminary evidence supporting the hypothesis that neurotoxicity risk is probably concentration dependent in this age group and presents with similar spectrum of symptoms as those described in adults.