In this episode, I’ll discuss the therapeutic monitoring of cefepime to avoid neurotoxicity.
Cefepime has the potential to cause severe neurotoxicity including seizures, myoclonus, or encephalopathy. The incidence of this neurotoxicity is variable however the risk is increased with excessive dosing or decreased clearance from renal impairment. Because high doses and decreased clearance are associated with cefepime related neurotoxicity it is logical to assume that increased cefepime plasma levels would identify patients at greater risk of neurotoxicity. However there is limited data available on this subject and a lack of a clear plasma level threshold for the development of neurotoxicity.
This prompted a group of authors to publish a retrospective review in the journal Pharmacotherapy with the goal of assessing the incidence of cefepime-related neurotoxicity as well as the relationship between cefepime levels and the development of neurotoxicity.
Data from approximately 500 patients was analyzed and an incidence of cefepime related neurotoxicity was 4.4%. The mean cefepime trough concentration in the patients who developed neurotoxicity was more than double the concentration in the non-neurotoxicity group at 61.8 mg/L. After a multiple regression model was applied to the data, cefepime trough concentration and renal dysfunction were independently associated with increased risk of neurotoxicity. In addition, a delay in checking cefepime levels of more than 72 hours was associated with triple the rate of neurotoxicity development.
This study provides an important starting point for identifying cefepime trough concentrations that are associated with neurotoxicity and giving potential targets for therapeutic monitoring to recognize the risk and hopefully prevent the development of neurotoxicity. Because therapeutic monitoring of beta-lactams is not widespread, in order to bring this knowledge to the bedside pharmacists will need to ensure their laboratory can report out cefepime concentrations with a turnaround time that provides results in a clinically meaningful time period
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