{"id":230,"date":"2017-12-05T02:06:46","date_gmt":"2017-12-05T02:06:46","guid":{"rendered":"https:\/\/docneuro.jz7sunfr-liquidwebsites.com\/cefepime-neurotoxicity\/"},"modified":"2020-01-20T20:19:52","modified_gmt":"2020-01-21T02:19:52","slug":"cefepime-neurotoxicity","status":"publish","type":"post","link":"https:\/\/docneuro.com\/cefepime-neurotoxicity\/","title":{"rendered":"Cefepime Neurotoxicity"},"content":{"rendered":"

Cefepime is a cephalosporin antibiotic typically used when broad spectrum coverage including Pseudomonas aerigonsa is needed. However, it can produce cefepime neurotoxicity with encephalopathy, myoclonus, reversible aphasia<\/a>, and\/or convulsive or subclinical seizures<\/a>.<\/p>\n

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Risk factors for cefepime neurotoxicity<\/h3>\n

Retrospective studies have shown neurotoxicity is most likely when the cefepime dose is insufficiently corrected for renal function, with renal dysfunction (even with renal dosing), older age, and abnormal brain imaging (1).<\/p>\n

Pharmacological studies suggest neurotoxicity is likely when the trough serum concentration is greater than 22 mg\/L (2). It is not practical to measure cefepime concentrations in most institutions, but pharmacokinetic modeling suggests that even doses as small as 2g daily can produce high serum concentrations when eGFR is less than 20 mil\/min.<\/p>\n

Effect of renal dysfunction<\/h3>\n

Cefepime is primarily cleared through the kidneys, with a half life of 2-3 hours with normal renal function (3). Renal dysfunction slows clearance, with an increase in half life to 12-13 hours at a GFR of 30 ml\/min. There is slower hepatic metabolism, so even in the absence of renal function cefepime would be cleared with a half life of ~22 hours.<\/p>\n

The net effect of renal dysfunction is to increase the trough concentration of cefepime. Using an aggressive dosing regimen (eg. total daily dose of 6 g) in a patient with a GFR of 15 could potentially result in a cefepime concentration 3-5 times the estimated toxic level.<\/p>\n

Clinical presentation of cefepime neurotoxicity<\/h3>\n

A subacute development of altered mental status over the course of 1-3 days is typical. The onset of encephalopathy can be delayed from initiation of cefepime 1-5 days, starting sooner the greater the mismatch between renal function and the cefepime dose.<\/p>\n

Findings on exam include disorientation that can progress to aphasia, positive myoclonus in the hands and face (see video from Neurology, below), and in extreme cases seizures (1).<\/p>\n