606 ■ The Annals of Pharmacotherapy ■ 2004 April, Volume 38 www.theannals.com C efepime is a fourth-generation cephalosporin com- monly used as first-line empirical treatment for im- munosuppressed patients with fever of unknown origin. Nonconvulsive status epilepticus is characterized by a de- creased level of consciousness without convulsions, epilep- tiform discharges in the electroencephalogram (EEG), and a good response to anticonvulsant agents. 1 Nonconvulsive status epilepticus causes many different neurologic deficits, particularly in alertness and cognitive functions, although it is a treatable disease with favorable prognosis. The vari- able clinical presentation, however, is the reason for fre- quent misdiagnoses. In addition, it is difficult to recognize in patients without a history of epilepsy because it usually occurs in severely ill patients who have many other poten- tial causes of decreased consciousness. 2 Cases of noncon- vulsive status epilepticus with cefepime therapy have mostly been reported in dialysis patients with chronic renal failure. 3 We describe a case in which the association of ce- fepime treatment and acute renal failure could have led to nonconvulsive status epilepticus. Case Report A 66-year-old woman with a history of hyperlipidemia and frequent upper respiratory tract infections was admitted to the hospital because of weakness, anorexia, productive cough, and shortness of breath of 2 months’ duration. Physical examination was unrevealing, but laboratory tests disclosed serum hemoglobin 5.5 g/dL, mild leukocytosis, and 30% blast cells in the peripheral blood. After complete hematologic studies, the diagnosis of M2 subtype of acute myeloid leukemia was established. Induction chemotherapy with idarubicin, cytarabine, and etoposide was started. The woman developed a new fever on the third day of chemo- therapy, with associated pancytopenia. Chemotherapy was discontinued, and cefepime 2 g every 8 hours was started. Blood cultures were repeat- edly negative. The fever did not subside, and 3 and 7 days later flucona- zole 200 mg every 24 hours and vancomycin 1 g every 12 hours, respec- Reversible Coma Secondary to Cefepime Neurotoxicity Sergio Abanades, Juan Nolla, Ana Rodríguez-Campello, Carme Pedro, Antonio Valls, and Magí Farré OBJECTIVE: To describe a case of cefepime neurotoxicity associated with acute renal failure that resulted in nonconvulsive status epilepticus. CASE SUMMARY: A 66-year-old woman with acute myeloid leukemia had fever on the third day of the initial chemotherapy cycle. Empiric antibiotic treatment with cefepime 2 g every 8 hours was started; fluconazole and vancomycin were subsequently added due to the persistence of fever. Ten days after initiation of cefepime, the patient developed acute renal failure followed by altered consciousness (Glasgow coma scale 6) associated with nonconvulsive status epilepticus. Cefepime was discontinued. Epileptiform activity in the electroencephalogram disappeared with clonazepam, and the patient regained consciousness 48 hours after cefepime withdrawal. DISCUSSION: Acute renal impairment combined with the use of cefepime may account for nonconvulsive status epilepticus. An objective causality assessment revealed that the adverse event was probably due to cefepime. Cefepime’s neurotoxic effects derive from high serum concentrations resulting from decreased renal clearance, increased unbound antibiotic, and blood–brain barrier dysfunction during uremia. CONCLUSIONS: The combination of cefepime treatment and acute renal failure may induce drug-related neurotoxicity. Nonconvulsive status epilepticus frequently passes unnoticed in severely ill patients without a history of epilepsy. This disorder should be included in the list of potential causes of coma. In this patient, early detection of nonconvulsive status epilepticus and withdrawal of the antibiotic resulted in full recovery. KEY WORDS: cefepime, nonconvulsive status epilepticus, renal failure. Ann Pharmacother 2004;38:606-8. Published Online, 24 Feb 2004, www.theannals.com, DOI 10.1345/aph.1D322 Author information provided at the end of the text. by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from