Cefepime neurotoxicity in the intensive care unit: a cause of severe, underappreciated encephalopathy.

INTRODUCTION: Cefepime, a broad spectrum antibiotic, is commonly prescribed in intensive care units (ICU) and may be an overlooked cause of neurologic symptoms such as encephalopathy, myoclonus, seizures, and coma. We aimed to characterize cefepime neurotoxicity in the ICU. METHODS: We performed a retrospective study of adult ICU patients treated with intravenous cefepime for at least 3 days between January 1, 2009 and December 31, 2011. The primary outcome was the development of cefepime neurotoxicity, with the likelihood of causality ascribed via a modified Delphi method. RESULTS: This study included 100 patients. The mean age was 65.8 years (± 12.7 years). The median daily average dose of cefepime was 2.5 (IQR 2.0 to 3.5) grams. The median treatment duration was 6 (IQR 4 to 10) days. Renal failure in any form was present in 84 patients. Chronic kidney disease affected 40 patients, and 77 had acute kidney injury. Cefepime neurotoxicity occurred in 15 patients. Of these, seven were considered definite cases, three probable, and five possible. Neurotoxic symptoms included impaired consciousness (n = 13), myoclonus (n = 11), disorientation (n = 6), and nonconvulsive status epilepticus (n = 1). The dose of cefepime was appropriately adjusted for renal clearance in 64 patients (75.3%) without cefepime neurotoxicity and four patients (28.6%) with neurotoxicity (P = 0.001). Chronic kidney disease was present in 30 patients (35.3%) without neurotoxicity and in 10 (66.7%) of those with neurotoxicity (P = 0.04). CONCLUSIONS: Critically ill patients with chronic kidney disease are particularly susceptible to cefepime neurotoxicity. Myoclonus and impaired consciousness are the predominant clinical manifestations. Neurotoxic symptoms occur more often when the cefepime dose is not adjusted for renal function, but can still occur despite those modifications.

The effects of penicillin and cephalosporin ingestions in children less than six years of age.

Oral antibiotic ingestions account for 1-2% of all pediatric exposures reported to regional poison information centers. The majority of these pediatric exposures involve the ingestion of penicillin or cephalosporin derivatives. How much can be ingested before gastric emptying is necessary is a controversial issue in the management of these cases. A study was designed to determine if children less than 6 years of age could safely ingest a maximum of 250 mg/kg of a penicillin or cephalosporin derivative without significant adverse effects. Sixty-one cases were prospectively collected. The average antibiotic amount ingested was 113.3 mg/kg (17.8-250.0 mg/kg). Each patient was evaluated for symptoms at the time of the initial call and at 6-12 degrees, 24 degrees, 48 degrees, and 72 degrees. Eighty-four percent of the children remained asymptomatic during the evaluation period. Eight of 13 symptomatic patients developed 1 or 2 episodes of diarrhea; 2 developed a rash. Amoxicillin suspension was involved in 70% of the cases, followed by cefachlor suspension 11%, and amoxicillin tablets 5%. Liquid preparations accounted for 90% of the cases and solid dosage forms, the remainder. The data strongly suggests that ingestions of less than 250 mg/kg of these products are not associated with significant outcomes and do not require gastric emptying.

A massive intrathecal cefazoline overdose.

This case report describes the clinical course of a patient who inadvertently received a massive intrathecal cefazoline overdose through a lumbar drain, which had been placed after trans-sphenoidal surgery for a pituitary adenoma. She received high-dose barbiturate therapy and was monitored with electroencephalography (EEG), somatosensory evoked potentials (SSEP), brainstem auditory evoked potentials (BAEP) and transcranial Doppler ultrasound (TCD). No cerebrospinal fluid (CSF) exchange was performed, but CSF was drained continuously with daily CSF-cefazoline level monitoring. Despite the extremely toxic dose, the patient soon recovered completely.