Characterizing Cefepime Neurotoxicity: A Systemic Review

Abstract

Background. Cefepime, a fourth-generation cephalosporin, is a commonly used parenteral antibiotic to treat neutropenic fever, healthcare-associated pneumonia, and other multidrug-resistant infections in the hospital setting. While initial clinical trials suggested a favorable safety profile, this has been debated in recent years, especially in light of neurotoxicity thought related to GABA antagonism. However, cefepime neurotoxicity has not been consistently characterized in the literature. Our objective is to provide clinicians with an evidence-based framework with which to recognize cefepime neurotoxicity. Methods. We searched the Cochrane Library and PubMed for English-language articles from inception through December 2015. Demographic and clinical data were abstracted from peer-reviewed studies and aggregated with cases of cefepime neurotoxicity encountered at a tertiary care academic medical center between February 2013 and August 2015. Results. We included 52 studies and 3 local cases, which represented 150 cases of cefepime neurotoxicity. Mean age was 67 years (±14, standard deviation), and 46% were women. Consistent with prior studies, most patients (87%) had renal dysfunction. Mean cefepime dose was 3.4g (±1.8 g) in 24 hours, which represented manufacturer-recommended renal dosing in 49%of cases.Mean number of days fromcefepime initiation to symptoms was 5 days (±3). The most common features were diminished level of consciousness (66%), disorientation/agitation (49%), and myoclonus (39%). Nonconvulsive status epilepticus (NCSE) was much more common than previously reported, with 32% of patients described with NCSE, while only 11% had convulsive seizures. A minority of patients (7%) developed aphasia.Most patients (77%) had an EEGperformed with 2 dominant electrographic patterns: triphasic waves consistent with metabolic encephalopathy versus epileptiform discharges. Sixteen percent of patients died while hospitalized, though deaths were only directly attributed to neurotoxicity in 2 cases. Conclusion. Cefepime neurotoxicity should be considered in older patients with renal dysfunction and new onset altered mental status or myoclonus, though NCSE due to cefepime may also be considerably more common than previously described.