cefepime and Epilepsy

Cephalosporins are beta-lactam antibiotics that are extensively used in medical practice and are reported to cause epileptic seizures in some patients. The primary cause of cephalosporin-induced convulsions is believed to be their ability to block GABAa receptors. However, direct evidence for the involvement of this mechanism has not yet been provided. The present study aims to investigate the ability of two cephalosporins - cefepime and ceftriaxone - to block inhibitory synaptic transmission in entorhinal cortex slices of rats. Using the whole-cell patch-clamp method, we found that millimolar concentrations of cefepime (IC

Topics: Animals; Anti-Bacterial Agents; Brain; Cefepime; Ceftriaxone; Cephalosporins; Epilepsy; GABA-A Receptor Antagonists; Inhibitory Postsynaptic Potentials; Ion Channel Gating; Ions; Neurons; Rats, Wistar; Receptors, GABA-A; Synaptic Transmission

To test the hypothesis that treatment with cefepime hydrochloride leads to higher incidence of periodic epileptiform discharges compared with treatment with other β-lactams.. Data from hospital pharmacy databases of patients treated with cefepime or meropenem during a 42-month period (from January 1, 2007, through June 30, 2010) were retrospectively crossed with data from the electroencephalography database for the same period.. Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.. Patients who underwent electroencephalographic testing while taking cefepime or meropenem were selected. Only electroencephalographic tests performed during the antibiotic treatment period were considered. Matches were compared with nurses' medication records to ensure that the antibiotic considered was effectively given.. Proportions of patients with continuous epileptiform discharges in the 2 groups were compared using the Fisher exact test.. A total of 1120 patients were treated with cefepime and 1572 patients with meropenem. Electroencephalographic testing was performed during treatment in 59 patients treated with cefepime and 80 treated with meropenem (5.26% vs 5.08%, P = .85). Continuous epileptiform discharges were present in 14 patients in the cefepime group and 3 in the meropenem group (1.25% vs 0.19%, P < .001). Blood creatinine concentration was elevated in 5 of the 17 patients (range, 1.5-4.2 mg/dL; reference range, 0.7-1.2 mg/dL), and liver enzyme levels were elevated in 5 patients. No patient had major electrolyte disturbances.. Our study showed a prevalence of electroencephalographic test results with continuous epileptiform discharges in 14 of 1120 patients receiving cefepime (1.25%) but only 3 of 1572 patients receiving meropenem (0.19%). Contrary to the results of previous case series, these electroencephalographic patterns occurred, in most cases, in patients with normal renal function. These results suggest that cefepime may be an independent risk factor for periodic epileptiform discharges, which are associated with worse outcomes. This finding could provide a partial explanation for the higher mortality rates reported in patients treated with cefepime compared with other β-lactams.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Belgium; Cefepime; Cephalosporins; Cross-Over Studies; Electroencephalography; Epilepsy; Female; Humans; Male; Meropenem; Middle Aged; Pharmacy Service, Hospital; Retrospective Studies; Thienamycins

Phenytoin, one of the most common antiepileptic drugs, is a major cause of antiepileptic drug hypersensitivity syndrome (AHS), which is a rare but potentially fatal complication. We herein report a 5-year-old boy who developed unexpected agranulocytosis with fever approximately one week after recovering from the typical symptoms of AHS, characterized by fever, rash, lymphadenopathy, and hepatitis, but lacking eosinophilia or lymphocytosis. High-dose steroid therapy for the former symptoms of AHS, and immunoglobulin, granulocyte colony-stimulating factor, and cefepime for the latter agranulocytosis were successfully performed. This unexpected progression from AHS to agranulocytosis shortly after recovering from the former should be recognized as another risk of AHS, possibly leading to a life-threatening condition.

Topics: Agranulocytosis; Anti-Bacterial Agents; Anticonvulsants; Cefepime; Cephalosporins; Chemical and Drug Induced Liver Injury; Child, Preschool; Disease Progression; Drug Hypersensitivity; Epilepsy; Exanthema; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lymphatic Diseases; Male; Phenytoin; Risk Factors; Steroids; Treatment Outcome

Topics: Aged; Cefepime; Cephalosporins; Epilepsy; Hodgkin Disease; Humans; Male; Peripheral Blood Stem Cell Transplantation; Staphylococcal Infections; Staphylococcus aureus; Transplantation, Autologous