Cefepime Induced Neurotoxicity Following A Regimen Dose-Adjusted for Renal Function: Case Report and Review of the Literature

Abstract

Introduction: Cefepime induced neurotoxicity (CIN) is commonly associated with renal dysfunction, however CIN can occur in patients with normal renal function or renally dose-adjusted regimens. Few reports of this kind have obtained cefepime concentrations to assist in diagnosis. Patient Case: A 42-year old female with a complex past medical history was transferred to our facility with chief complaint of worsening shock and respiratory failure, and the patient was also noted to be hypernatremic, experiencing diabetic ketoacidosis (DKA), and acute kidney injury (AKI). Her DKA resolved and hypernatremia and AKI began to improve. As a result, cefepime was dose-adjusted for renal function estimated by the Cockcroft-Gault (CG) equation. Her hospital course was complicated by persistent altered mental status (AMS), preventing extubation. Cefepime was discontinued due to concern for CIN, and a concentration was obtained 13-hours after the last dose which was elevated at 49 µg/mL. Two days following cefepime discontinuation, the patient’s mental status improved allowing for successful extubation. The patient remained stable and was discharged to an acute care floor and then ultimately back to home. Conclusion: CIN should be part of a wider differential diagnosis for patients experiencing encephalopathy, and inaccurate renal function estimation may be a risk factor for developing CIN. Furthermore, therapeutic drug monitoring (TDM) may serve as an important clinical tool in diagnosing and managing CIN.

Cefepime-induced neurotoxicity in non-critically ill medical patients: a retrospective cohort study

“…First, the duration of cefepime administration in this study was around 5 days compared to the other studies having relatively longer times to detect the adverse effects [15,22,40]. Second, the therapeutic drug monitoring (TDM) might appeal given the observed association between higher levels and neurotoxicity [41][42][43][44][45][46], however, it was not available at our institution. The neurotoxicity event in our sample was low.…”

Pharmacokinetics of YK‐1169 in healthy subjects and pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation

“…Cefepime-induced neurotoxicity is more likely in patients with renal impairment or potential brain abnormalities (such as Parkinsonism, stroke and schizophrenia) and the elderly population. 35,36 The neurotoxicity of cefepime is a concentration-dependent competitive Υ-aminobutyric acid antagonism. 37 Previous studies have defined excessive serum trough concentrations of cefepime as >20 mg/L, and these data indicated a five-fold increase in neurologic risk when this threshold was exceeded.…”

“…Cefepime‐induced neurotoxicity is a safety concern in clinical practice. Cefepime‐induced neurotoxicity is more likely in patients with renal impairment or potential brain abnormalities (such as Parkinsonism, stroke and schizophrenia) and the elderly population 35,36 . The neurotoxicity of cefepime is a concentration‐dependent competitive ϒ‐aminobutyric acid antagonism 37 .…”

Review on Characterization, Properties, and Analytical Methods of Cefepime

“…There should be a consideration for CP neurotoxicity in older patients with myoclonus who are suffering recently from alterations in mental status and renal impairment [ 23 – 26 ]. Seizures are the most common adverse reaction of cefepime on the central nervous system.…”