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Cefepime neurotoxicity/ #encephalopathy/ #delirium is something we see frequently on the neurology consult service. Several new papers further explore this adverse effect. A quick thread 1/n https://twitter.com/DRxDray/status/1278673510794215426
Cefepime neurotoxicity was first described in 1999 by Wong et al. in a 40 year old patient on dialysis who developed delirium, asterixis, myoclonus, and a generalized convulsion/seizure https://pubmed.ncbi.nlm.nih.gov/10489256/ 2/n
The overlap between encephalopathy and seizures continues in more recent literature, but as in most critical care, encephalopathy is likely more common than seizures. https://pubmed.ncbi.nlm.nih.gov/31201049/ 3/n
On EEG, generalized discharges, sometimes with triphasic morphology, can be seen with cefepime neurotoxicity, and they can improve with drug cessation 4/n https://pubmed.ncbi.nlm.nih.gov/11113245/
Therapy for cefepime neurotoxicty? As with most #delirium, less (medication) is more: "Recovery was related to cephalosporin withdrawal rather than antiepileptic therapy." https://pubmed.ncbi.nlm.nih.gov/31201049/ 5/n
Cefepime neurotoxicity has been increasingly described in the literature https://pubmed.ncbi.nlm.nih.gov/?term=cefepime+%28encephalopathy+OR+delirium+OR+neurotoxicity%29 (apologies to papers I have not cited in this thread) 6/n
In Khan et al. from @RushDOIM, 6.5% of patients with moderate or severe kidney dysfunction developed cefepime associated neurotoxicity, mostly altered mental status (92%) of various types https://pubmed.ncbi.nlm.nih.gov/32147247/ 7/n
There was a suggestion that more severe renal dysfunction and higher doses of cefepime were associated with increased likelihood of neurotoxicity, but neither reached stat significance and the study was perhaps not powered for this 8/n
Singh et al. from @MayoClinicNeuro looked at a larger retrospective cohort from 152,999 ICU patients, and identified patients with acute encephalopathy and matched controls. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329265/ 9/n
Patients with acute encephalopathy were more likely to have received cefepime, which was associated with an odds ratio of 1.24 for the development of acute encephalopathy in multivariable analyses. 10/n
"The average time from the administration of cefepime to the development of signs of neurotoxicity was 4 days (IQR 1–6 days)." Look at current meds but also back at recent meds when evaluating encephalopathy and delirium 11/n
"Cefepime was associated with prolonged acute encephalopathy duration in patients with" kidney dysfunction, but was also associated with acute encephalopathy even when kidney dysfunction was taken into account. 12/n
As a neurologist, I should note that both studies unfortunately excluded patients with primarily neurologic disease, which is common practice in many general studies of #encephalopathy or #delirium. 13/n
Also many other antibiotics can be associated with #encephalopathy or #delirium, as in work by @shamik_b, @AaronLBerkowitz, and colleagues https://pubmed.ncbi.nlm.nih.gov/26888997/ 14/n
Thank you to all these groups for their work. For more thoughts on the nomenclature of #encephalopathy vs #Delirium, see this recent position paper https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210231/ which was affirmed by @AANMember 15/end
