Cefepime-Induced Neurotoxicity

Abstract

Cefepime is a common antibiotic used to treat various infections such as pneumonia, skin infections, and intra-abdominal infections due to its broad gram-positive and gram-negative spectrum. However, patients with acute kidney injury, end-stage renal disease, and renal transplantation are disproportionately at higher risk of developing complications from administration of cefepime, secondary to its predominant renal excretion. Current guidelines prescribe cefepime renal-dosing, dependent on the glomerular filtration rate, to prevent toxicity. This study presents a rare case where an acutely hospitalized patient undergoing chronic renal transplant rejection was administered renal-dose cefepime. Despite renal dosing, the patient developed neurotoxicity that manifested as delirium, inability to tolerate oral intake, and non-convulsive status epilepticus. Solely adjusting for renal dysfunction may be inadequate to prevent the accumulation of cefepime metabolites, which may present in an atypical manner in the patient. Such possibilities emphasize the need for continued evaluation of a patient's mentation in case of cefepime administration. Cefepimeinduced neurotoxicity incidences need to be evaluated and researched thoroughly.

The incidence and predictors of antibiotic-associated encephalopathy: a multicenter hospital-based study

“…Prior studies on AAE have focused on individual antibiotic effects on neurological dysfunction by clinical manifestations and patient susceptibility depending on the risk factors of older age, comorbidities, and metabolic dysfunction 5 , 7 , 10 – 12 , 14 , 18 , 19 . To our knowledge, this is the first large study to incorporate a wide range of antibiotics utilized for cases ranging in severity from minor to severe in a tertiary hospital setting.…”

“…Based on the unique actions on the CNS associated with each type of antibiotic, combination use is expected to increase the chance of encephalopathy. Type 1 antibiotics are thought to cause encephalopathy through disruption of inhibitory synaptic transmission leading to excitotoxicity through ligand-gated ion channel ɤ-aminobutyric acid class A receptor (GABA A R) binding 5 , 9 , 11 , 12 , 14 , 18 . β-lactams bind GABA A R either competitively or non-competitively and inhibit intracellular influx of chloride, impeding inhibitory postsynaptic potential.…”

“…Serious adverse CNS effects of antibiotics are reported with a frequency < 1% 7 , 8 . Recent reports on neurologic toxicity from antibiotics are mounting, with a rate of 15% associated with the use of the fourth-generation cephalosporin cefepime 5 , 6 , 9 – 12 . The incidence of cefepime-induced encephalopathy was higher especially in patients with lower values of glomerular filtration rate (GFR) and dialysis 13 .…”

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

“…Patients with acute kidney injury and chronic kidney disease were at higher risk [29]. Several studies correlating neurotoxicity with cefepime were mainly in the patients with certain degree of impaired kidney function [30][31][32][33][34][35][36][37], however neurotoxicity was also reported in patients of normal kidney function [38,39].…”

Tremor as a Rare Manifestation of Cefepime Neurotoxicity

“…Incidence less than 1% but greater than 0.1% Colitis (including pseudomembranous colitis), diarrhea, erythema, fever, headache, nausea, oral moniliasis, pruritis, urticaria, vaginitis, vomiting, and anemia Cefepime is renally excreted with a creatinine clearance of 74.0 (±15.0) mL/min, and research has shown a decrease in cefepime total body clearance as a function of creatinine clearance [3]. Dosage adjustment appropriate for patients' degree of renal impairment should be done for patients with renal dysfunction, those receiving hemodialysis, and geriatric patients with renal impairment having experienced serious adverse events after being given unadjusted doses of cefepime [6]. The safety of cefepime has been studied in the elderly population (65 and over) and there were no additional risks as long as the dosage was adjusted as appropriate if the patient's creatinine clearance was 60 mL/min or less.…”