title: Cefepime neurotoxicity in the intensive care unit: a cause of severe, underappreciated encephalopathy.
abstract: BACKGROUND
  Cefepime, a broad spectrum antibiotic, is commonly prescribed in intensive care units (ICU) and may be an overlooked cause of neurologic symptoms such as encephalopathy, myoclonus, seizures, and coma. We aimed to characterize cefepime neurotoxicity in the ICU.
  
  
  METHODS
  We performed a retrospective study of adult ICU patients treated with intravenous cefepime for at least 3 days between January 1, 2009 and December 31, 2011. The primary outcome was the development of cefepime neurotoxicity, with the likelihood of causality ascribed via a modified Delphi method.
  
  
  RESULTS
  This study included 100 patients. The mean age was 65.8 years (± 12.7 years). The median daily average dose of cefepime was 2.5 (IQR 2.0 to 3.5) grams. The median treatment duration was 6 (IQR 4 to 10) days. Renal failure in any form was present in 84 patients. Chronic kidney disease affected 40 patients, and 77 had acute kidney injury. Cefepime neurotoxicity occurred in 15 patients. Of these, seven were considered definite cases, three probable, and five possible. Neurotoxic symptoms included impaired consciousness (n = 13), myoclonus (n = 11), disorientation (n = 6), and nonconvulsive status epilepticus (n = 1). The dose of cefepime was appropriately adjusted for renal clearance in 64 patients (75.3%) without cefepime neurotoxicity and four patients (28.6%) with neurotoxicity (P = 0.001). Chronic kidney disease was present in 30 patients (35.3%) without neurotoxicity and in 10 (66.7%) of those with neurotoxicity (P = 0.04).
  
  
  CONCLUSIONS
  Critically ill patients with chronic kidney disease are particularly susceptible to cefepime neurotoxicity. Myoclonus and impaired consciousness are the predominant clinical manifestations. Neurotoxic symptoms occur more often when the cefepime dose is not adjusted for renal function, but can still occur despite those modifications.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Fugate
authors.forename: Ejaaz A
authors.initials: EA
authors.lastname: Kalimullah
authors.forename: Sara E
authors.initials: SE
authors.lastname: Hocker
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Clark
authors.forename: Eelco F M
authors.initials: EF
authors.lastname: Wijdicks
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Rabinstein
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000506:poisoning / Q000627:therapeutic use; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000506:poisoning* / Q000627:therapeutic use; D003244:Consciousness Disorders / Q000139:chemically induced*; D003693:Delirium / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008499:Medical Records / Q000706:statistics & numerical data; D008910:Minnesota; D009207:Myoclonus / Q000139:chemically induced*; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000188:drug therapy; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime