Cefepime-Associated Neurotoxicity in a Pediatric Patient With Stage V Chronic Kidney Disease

Abstract

Background Studies in adult patients suggest cefepime can cause neurotoxicity, including disorientation, seizures, and coma, particularly when present at high concentrations. Patients with underlying kidney dysfunction or central nervous system anomalies are at particularly high risk. There is a relative paucity of pediatric literature on the neurotoxic effects of cefepime. Case Report Herein is reported the case of a 2-year-old patient with chronic kidney disease receiving cefepime for Serratia marcescens bacteremia who experienced agitation, tremor, and inconsolability in the setting of an elevated cefepime trough that improved with cefepime discontinuation alone. Conclusions Pediatric patients with acute and chronic kidney disease are at risk of cefepime-related neurologic changes. Therapeutic drug monitoring for cefepime in patients with kidney dysfunction or baseline neurologic abnormalities may help inform appropriate antimicrobial dosing and avoidance of toxicity.

β-lactam precision dosing in critically ill children: Current state and knowledge gaps

“…Cefepime-associated neurotoxicity has been abundantly reported in adults with studies demonstrating increased risk of neurotoxicity in patients with underlying neurologic abnormalities and renal dysfunction, often when trough concentrations are above 20–30 mg/L ( Lamoth et al, 2010 ; Huwyler et al, 2017 ; Payne et al, 2017 ; Boschung-Pasquier et al, 2020 ; Lau et al, 2020 ) A toxicodynamic study recommends using a highest trough threshold of 50 mg/L for precision dosing ( Lau et al, 2021 ). Suspected cefepime-associated neurotoxicity in children is limited to case reports, ( Alpay et al, 2004 ; Landgrave et al, 2012 ; Guzman-Limon et al, 2017 ; Shah and Bland, 2021 ; Hambrick et al, 2022 ), all in children with renal dysfunction; one case reported a cefepime concentration of >60 mg/L days after cefepime discontinuation and another reported a trough concentration of 80 mg/L when the patient was experiencing neurotoxic symptoms. Larger studies to investigate the relationship between cefepime exposures and neurotoxicity specifically in patients at risk of cefepime-associated neurotoxicity (i.e., patients with abnormal neurologic baseline, altered blood-brain barrier integrity, or renal dysfunction) would help identify pediatric-specific toxicity target thresholds to avoid with precision dosing.…”