Cefepime-induced encephalopathy

The most common adverse event of cefepime on the central nervous system is seizure.1.Neu H.C. Safety of cefepime: a new extended-spectrum parenteral cephalosporin.Am. J. Med. 1996; 100: 68S-75SAbstract Full Text PDF PubMed Google Scholar Cefepime induced encephalopathy, however, has been only rarely reported.2.Fishbain JT, Monahan TP, Canonico MM. Cerebral manifestations of cefepime toxicity in a dialysis patient. Neurology 2000;55.Google Scholar, 3.Jallon P. Fankhauser L. Du-Pasquier R. et al.Severe but reversible encephalopathy associated with cefepime.Neurophysiol. Clin. 2000; 30: 383-386Crossref PubMed Scopus (77) Google Scholar A 60-year-old diabetic patient with end stage renal disease on hemodialysis was admitted with left pleuritic chest pain and productive cough. He was afebrile and hemodynamically stable, with a systolic apical heart murmur, bilateral basal lung crackles, and hepatomegaly. Laboratory data: Hemoglobin 10.4 g/dl, Hematocrit 32%, WBCs 11000/mm3, PMN’s 91%, creatinine 10.9 mg/dl and BUN 64 g/l. Chest film showed right middle lobe infiltrates and cefepime (2 g/d) was started empirically. Five days later, the patient started to show confusion, have visual and auditory hallucinations, and agitation with no focal deficit on physical examination. These neurological symptoms did not improve upon further dialysis over two days; cefepime was then stopped. Within one day, he started to improve, and two days later, he returned to his baseline level of mental status. Upon re-interviewing his wife and reviewing his medical record, he was found to have had hallucinations and confusion after taking ceftazidime, a year earlier. Cephalosporin induced neurotoxicity has been reported with ceftazidime, ceftriaxone, and cefuroxime.4.Herishanu Y.O. Zlotnik M. Mostoslavsky M. Podgaietski M. Frisher S. Wirguin I. Cefuroxime-induced encephalopathy.Neurology. 1998; 50: 1874-1876Crossref Scopus (35) Google Scholar, 5.Klion A.D. Kallsen J. Cowl C.T. Nauseef W.M. Ceftazidime-related nonconvulsive status epilepticus.Arch. Intern. Med. 1994; 154: 586-589Crossref PubMed Google Scholar, 6.Martinez-Rodriguez J.E. Barriga F.J. Santamaria J. et al.Nonconvulsive status epilepticus associated with cephalosporines in patients with renal failure.Am. J. Med. 2001; 111: 115-119Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar The main predisposing factors are pre-existing CNS abnormalities and renal impairment with excessive dosing of the antibiotic.7.Calandra G. Lydick E. Carrigan J. Weiss L. Guess H. Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastin.Am. J. Med. 1988; 84: 911-918Abstract Full Text PDF PubMed Scopus (203) Google Scholar Our patient was given two grams of cefepime daily based on recommendations of Gilbert et al.8.Dosage of antimicrobial drugs in patients with renal impairment. In: Gilbert DN, Moellering RC, Sande MA, editors. The Sanford guide to antimicrobial therapy. 28th ed. Antimicrobial Therapy, 1998:117.Google Scholar He developed confusion, hallucinations and agitation, which progressed over one week despite intensification of hemodialysis and the absence of electrolyte disturbances. Cefepime was then stopped due to circumstantial evidence and the previous occurrence of hallucinations with ceftazidime the year before. A CT scan of the brain was not requested due to the lack of focal motor or sensory deficit, and an EEG was not carried out because of the rapid clinical improvement after stopping cefepime. Neurotoxicity of cefepime has been reported before and the spectrum of manifestations has been broad including: confusion, hallucinations, agitation, convulsions, tremor, delirium and coma (Table 1). The latency of neurotoxicity, which is the period between the start of cefepime treatment and neurologic manifestations, varied between one and ten days, and all neurological symptoms regressed within two to seven days after stopping the antibiotic infusion. Almost all patients affected have had renal failure and the dose of cefepime was relatively high for the level of renal failure. The newer Sanford guides to antimicrobial therapy (2001 to 2003) suggest a smaller dose of cefepime according to the creatinine clearance.11.Dosage of antimicrobial drugs in patients with renal impairment. In: Gilbert DN, Moellering RC, Sande MA, editors. The Sanford guide to antimicrobial therapy, 33rd ed. Antimicrobial Therapy, 2003:128.Google Scholar Thus, if a patient on cefepime develops neurological symptoms, drug neurotoxicity should be considered.Conflict of interest: No conflicting interest declared.Table 1Cases of cefepime induced neurotoxicity reported in the literature.StudyYearAge (Year)SexCefepime doseRFNumber of casesClinical findingsDiagnosisLatency (days)TreatmentFishbain et al.2.Fishbain JT, Monahan TP, Canonico MM. Cerebral manifestations of cefepime toxicity in a dialysis patient. Neurology 2000;55.Google Scholar200074F2 g/24 hYes1Confusion, delirium, comaEEG*, drug level4D/C ABJallon et al.3.Jallon P. Fankhauser L. Du-Pasquier R. et al.Severe but reversible encephalopathy associated with cefepime.Neurophysiol. Clin. 2000; 30: 383-386Crossref PubMed Scopus (77) Google Scholar200057–917M/12F2–6 g/24 hYes19Confusion, hallucinationEEG*1–7D/C ABMartinez-Rodriguez et al.6.Martinez-Rodriguez J.E. Barriga F.J. Santamaria J. et al.Nonconvulsive status epilepticus associated with cephalosporines in patients with renal failure.Am. J. Med. 2001; 111: 115-119Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar200154–863M/3F1–2 g/24 hYes6Agitation, confusion, myoclonus,EEG*1–10D/C AB, Clonazepam, phenytoinChetaille et al.9.Chetaille E. Harly I. deCagny B. Gras-Champel V. Decocq G. Andrejak M. Crises convulsives associes a un surdosage en cefepime.Therapie. 1997; 52: 167-168Google Scholar1997F3 g/24 hYes1Confusion, convulsionEEG**D/C ABDixit et al.10.Dixit S. Kurle P. Buyan-Dent L. Sheth R.D. Status epilepticus associated with cefepime.Neurology. 2000; 54: 2153-2155Crossref PubMed Scopus (61) Google Scholar200044/28M/F2 g/24 hYes2Confusion, tremor, hyperreflexia, seizureEEG***1D/C ABM: male, F: female, h: hour, *: triphasic wave encephalopathy, **: irritative state, ***: continuous generalised sharp wave with slow activity, RF: renal failure, D/C: discontinuation of drugs, g: grams, h: hour, AB: antibiotic. Open table in a new tab M: male, F: female, h: hour, *: triphasic wave encephalopathy, **: irritative state, ***: continuous generalised sharp wave with slow activity, RF: renal failure, D/C: discontinuation of drugs, g: grams, h: hour, AB: antibiotic.