cefepime and Hallucinations

High-dose cefepime therapy is recommended for febrile neutropenia. Safety issues have been raised in a recent meta-analysis reporting an increased risk of mortality during cefepime therapy. Cefepime-related neurological toxicity has been associated with overdosing due to severe renal dysfunction. This study aimed to investigate the association between cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients. Cefepime trough concentrations (by high-performance liquid chromatography) were retrospectively analyzed for 30 adult febrile neutropenic patients receiving the recommended high-dose regimen (6 g/day for a glomerular filtration rate [GFR] of >50 ml/min). The dose adjustment to renal function was evaluated by the ratio of the cefepime daily dose per 100 ml/min of glomerular filtration. The association between cefepime plasma concentrations and neurological toxicity was assessed on the basis of consistent neurological symptoms and/or signs (by NCI criteria). The median cefepime concentration was 8.7 mg/liter (range, 2.1 to 38 mg/liter) at a median of 4 days (range, 2 to 15 days) after the start of therapy. Neurological toxicity (altered mental status, hallucinations, or myoclonia) was attributed to cefepime in 6/30 (20%) patients (median GFR, 45 ml/min; range, 41 to 65 ml/min) receiving a median dose of 13.2 g/day per 100 ml/min GFR (range, 9.2 to 14.3 g/day per 100 ml/min GFR). Cefepime discontinuation resulted in complete neurological recovery for five patients and improvement for one patient. A multivariate logistic regression model confirmed high cefepime concentrations as an independent predictor of neurological toxicity, with a 50% probability threshold at ≥22 mg/liter (P = 0.05). High cefepime plasma concentrations are associated with neurological toxicity in febrile neutropenic patients with mild renal dysfunction. Careful adherence to normalized dosing per 100 ml/min GFR is crucial. Monitoring of plasma concentrations may contribute to preventing neurological toxicity of high-dose therapy for this life-threatening condition.

Topics: Adult; Aged; Cefepime; Cephalosporins; Female; Glomerular Filtration Rate; Hallucinations; Humans; Male; Middle Aged; Nervous System; Neutropenia; Retrospective Studies

Electroencephalography is a useful tool for the diagnosis and follow-up of toxic and metabolic encephalopathies. A pseudo-periodic pattern can indicate various brain pathologies and causes of mental confusion. Among these, cefepime encephalopathy should always be considered, particularly in cases of renal failure, because of the reversibility of the symptoms at drug withdrawal.

Topics: Aged; Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Electroencephalography; Female; Hallucinations; Humans; Mental Disorders

In this study, a report has been made of 19 cases of severe encephalopathy in patients with renal impairment who were treated during the last three years for various infections with cefepime, a new parenteral cephalosporin antibiotic. All patients (aged 57 to 91 years) presented a prolonged confusional state associated with diffuse rhythmic non-reactive triphasic sharp waves on the EEG. All the electroclinical symptomatology disappeared within 24-48 hours after discontinuation of drug administration. A clear relation was found between encephalopathy and cefepime intake. These observations underline the fact that the cefepime dosage should be reduced in renally impaired patients.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Cefepime; Cephalosporins; Confusion; Creatinine; Electroencephalography; Female; Hallucinations; Humans; Kidney Diseases; Male; Middle Aged; Myoclonus