JNEPHROL 2008; 21: 526-534 ORIGINAL ARTICLE 526 ABSTRACT Background: Cefepime is a widely used antibiotic. How- ever, it can cause encephalopathy, which has been in- creasingly described in the literature, occurring mainly in patients with impaired renal function. The primary objec- tive in this study was to measure the incidence of ce- fepime-induced encephalopathy and determine potential risk factors for its occurrence. Methods: In the period from February 2005 to February 2006, a prospective cohort study was conducted, which followed 498 patients using cefepime. Other metabolic problems were ruled out for all patients with clinical sus- picion of encephalopathy and, when cefepime was the probable cause, electroencephalographic (EEG) tests were performed to assist in the diagnosis, with the first performed during cefepime use and another performed at least 48 hours following drug discontinuation and/or clinical improvement. Results: Among patients selected for this study (n=498), 5 were diagnosed with cefepime-induced encephalopa- thy, thus indicating a cumulative incidence of approxi- mately 1% (0.01), 387 had glomerular filtration rate (GFR) ≥60 ml/min and 111 had GFR <60 ml/min. Among the lat- ter, 5 patients developed cefepime-induced en- cephalopathy. Mean GFR value in patients with en- cephalopathy (n=5) was 17.20 ml/min (SD ±10.75 ml/min) and, in patients without encephalopathy (n=106) it was 32.59 ml/min (SD ±14.89 ml/min) (p=0.025). Conclusion: The development of cefepime-induced en- cephalopathy seems to be related to the severity of im- pairment in glomerular filtration. Key words: Cefepime, Encephalopathy, Incidence, Neuro- toxicity, Renal failure INTRODUCTION Cefepime is a semisynthetic cephalosporin, classified as fourth-generation drug, used in the treatment of serious infec- tions, both nosocomial and those acquired in the community (1, 2). This antimicrobial drug had its safety profile tested by Neu (3) who found a few neurological adverse effects in 61 of 2,032 patients (3.0%). There are many case reports in the lit- erature regarding cefepime-induced encephalopathy, with at least 47 cases of this clinical condition being identified (4-15), especially in patients with impaired renal function (4-11, 13, 15). Our study is the first with a prospective cohort design to evaluate the encephalopathy related to this drug and degree of renal function. Cefepime encephalopathy can lead to a nonconvulsive sta- tus epilepticus (NCSE) (4, 5, 7-9, 11-15), presenting neuro- logical and electroencephalographic manifestations that are reversible in nature following drug discontinuation (16). The primary objectives of this study are to measure the inci- dence of encephalopathy induced by the use of cefepime and to identify potential risk factors related to its occurrence and, in addition, to describe the clinical and electroen- cephalographic manifestations occurring in patients with encephalopathy. SUBJECTS AND METHODS In the period from February 2005 to February 2006, a prospective cohort study was conducted, where all patients prescribed cefepime were identified through the Hospital de Clínicas de Porto Alegre (HCPA), Brazil, computerized pre- scription system. A list of these patients was provided by Erwin Otero Garcés 1 , Mauro Francisco Andrade de Azambuja 2 , Daiandy da Silva 3 , José Augusto Bragatti 1,4 , Thalita Jacoby 1,3 , Fernando Saldanha Thomé 5 1 Post-Graduation Program in Medical Sciences, Universidade Federal de Rio Grande do Sul, Porto Alegre, RS - Brazil 2 Internal Medicine Service, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS - Brazil 3 Clinical Pharmacy Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS - Brazil 4 Electroencephalography Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS - Brazil 5 Internal Medicine Department, Faculty of Medicine, Universidade Federal de Rio Grande do Sul, Porto Alegre, RS - Brazil Renal failure is a risk factor for cefepime-induced encephalopathy www.sin-italy.org/jnonline – www.jnephrol.com