Clinical pharmacology fellow Cincinnati Children's Hospital Medical Center Cincinnati, Ohio, United States
Background: Cefepime is a commonly used antibiotic for hospital acquired infections. Actual cefepime concentrations after standard dosing in critically ill patients display significant inter-individual variation. This high variability is concerning because cefepime-induced-neurotoxicity in adults is a concentration-dependent adverse effect when concentrations are markedly elevated. Such neurotoxicity symptoms can range from confusion to seizures and coma. Children with neurologic symptoms attributed to cefepime have been described in case reports but has not been interrogated systematically. Objective: To evaluate the presence and types of neurological concerns present in children receiving cefepime, and to evaluate which, if any, symptoms occur with greater prevalence among patients exposed to abnormally high cefepime concentrations. Design/Methods: This is a retrospective analysis of patients enrolled in an existing IRB approved study of cefepime pharmacokinetics in the pediatric intensive care unit (ICU). Sequentially enrolled patients were included if they had ≥2 cefepime samples collected for concentration measurement and ≥48 h of cefepime course available for analysis (n=100 patients). Electronic medical records were reviewed for documented neurologic symptoms (altered mental status, change in level of consciousness, myoclonus/tremors, hallucinations, irritability, seizures), delirium score, and orders for specific neurologic testing (head imaging, cerebrospinal fluid analysis, electroencephalography, or neurology consult). Cefepime concentrations were measured from opportunistic blood samples and PK parameters were estimated using a published model and Bayesian estimation in the modeling program MWpharm++. The relationship between cefepime-associated neurotoxicity symptoms and blood concentrations will be assessed by logistic regression.
