1. Crazy for Cefepime? Cefepime neurotoxicity in an ICU patient with normal renal function. Allison Rogers MD, Jeremey Walker MD, Vera Bittner MD 69 year old white female with advanced heart failure admitted for inotropic support and diuresis. Broad spectrum antibiotics initiated for suspected sepsis. After 72 hours of antimicrobials, patient developed acute mental status changes. Physical exam notable only for mental status changes. Vital signs stable. Atypical antipsychotics administered without improvement. Treatment Discontinuation of cefepime Supportive measures - Consensus favors benzodiazepine use for agitation as neurotoxicity GABA mediated - Avoid over-sedation Antipsychotics or antiepileptics - No proven benefit - Literature suggests conservative approach References Patient Presentation Take Home Points Cefepime encephalopathy is an under-recognized cause of ICU delirium In patients with acute mental status changes, consider cefepime when reviewing medications. Consider EEG if uncertain etiology. Treatment of cefepime encephalopathy is discontinuation of cefepime and supportive care... Neurotoxicity is a known, but rare complication of cephalosporins due to competitive binding of GABA receptors causing increased excitatory neurotransmission. Symptoms include confusion, hallucinations, myoclonus, seizure, and coma. Recent observational study reported 15% of exposed patients within a critically ill population developed cefepime-induced neurotoxicity. Introduction Qingping S, Feng D, Ran S, Yan L, HaoYu Y, Meiling Y. Drug use evaluation of cefepime in the first affiliated hospital of Bengbu medical college: a retrospective and prospective analysis. BMC Infectious Diseases. 2013;13:160. doi:10.1186/1471-2334-13-160. Cephalosporin-induced neurotoxicity: clinical manifestations, potential pathogenic mechanisms, and the role of electroencephalographic monitoring. Marie Francisca Grill, Rama Maganti Ann Pharmacother. 2008 December; 42(12): 1843–1850. Published online 2008 November 25. doi: 10.1345/aph.1L307. Fugate et al.: Cefepime neurotoxicity in the intensive care unit: a cause of severe, underappreciated encephalopathy. Critical Care 2013 17:R264. Chow KM, Szeto CC, Hul AC, et al. Retrospective review of neurotoxicity induced by cefepime and ceftazidime. Pharmacotherapy 2003;23: 369-73. FDA Drug Safety Communication: Cefepime and risk of seizure in patients not receiving dosage adjustments for kidney impairment.. Accessed 1/28/16.http://www.fda.gov/Drugs/DrugSafety/ucm309661.htm Gaspard, N. et. al. Nonconvulsive Status Epilepticus. In: UpToDate, Eichler A. (Ed), UpToDate, Waltham, MA. (Accessed on January 28, 2016). Recognize cefepime as a cause of delirium even in patients with preserved renal function. Describe the clinical manifestations and management of cefepime induced neurotoxicity. Learning Objectives Day 1 Admitted to Cardiac Care unit Day 3 Day 8 Disease Course Mute with myoclonus and spasticity Day 10 Tinsley Harrison Internal Medicine Residency Program Disoriented, agitated on exam Day 7 Broad spectrum antibiotics started for suspected sepsis Day 6 Cefepime Vancomycin ICU Delirium Cefepime Encephalopathy Almost all patients initially exhibit confusion and disorientation One-third progress to myoclonus One-tenth epileptiform activity Onset seen on antibiotic day 1-10 Typically seen in patients: - older than 50 - with underlying renal dysfunction Long-term prognosis unclear IV inotropes and diuresis initiated Cefepime discontinued Following commands, paranoid Back to baseline EEG performed Day 11 CT head negative Sedating meds discontinued Common drugs causing delirium: -Digoxin (level 1.3) -Anticholinergics -Anticonvulsants -Benzos -Opioids -Corticosteroids -Antibiotics Supportive Measures Identify Underlying Causes Manage Agitation Metabolic Drug Induced Electrolytes Infectious Organ failure Albumin 4.5, Tbili 1.0 Ammonia 26 Alk phos 99 ALT/AST 22 ABG 7.46/36/83/26 CT head negative Blood cultures/UA/ CXR all negative EEG findings Electroencephalogram showing generalized sharp and slow wave discharges. http://dx.doi.org/10.1016/j.yebeh.2005.09.010 Common causes excluded: -Hyper/hyponatremi a -Hypoglycemia -Acidosis -Uremia Common causes excluded: -AKI -Hepatic injury -Stroke 136 99 15 112 3.9 24 0.6 9.4 8.9 252 30 Common causes excluded: -Bacteremia -Pneumonia -Urinary tract infection