Clinical, Electroencephalographic Features and Prognostic Factors of Cefepime-Induced Neurotoxicity: A Retrospective Study

  • Han-Tao Li
  • Chih-Hong Lee
  • Tony Wu
  • Mei-Yun Cheng
  • Wei-En Johnny Tseng
  • Chun-Wei Chang
  • Hsiang-Yao Hsieh
  • Hsing-I Chiang
  • Chih-Yin Lin
  • Bao-Luen Chang
  • Wey-Ran Lin
  • Siew-Na LimEmail author
Original Work



The incidence of cefepime-induced neurotoxicity (CIN) has been previously underestimated, and there have only been sporadic reports from critical neurological settings. The present study aimed to investigate the potential factors associated with disease development, electroencephalography (EEG) sub-classification, and outcome measures.


The 10-year medical records of patients who underwent EEG between 2007 and 2016 at a tertiary medical center in Taiwan, and developed encephalopathy after cefepime therapy were retrospectively reviewed. Age- and sex-matched controls were included for further analysis. Demographic data, the occurrence of clinical seizures, non-convulsive status epilepticus (NCSE), use of antiepileptic drugs (AEDs), receiving maintenance or urgent hemodialysis, EEG findings, and functional outcomes were analyzed. The Chi-square test and a logistic regression model were applied to survey significant prognostic factors relating to mortality.


A total of 42 CIN patients were identified, including 25 patients from wards and 17 from intensive care units; their mean age was 75.8 ± 11.8 years. Twenty-one patients (50%) had chronic kidney disease, and 18 (43%) had acute kidney injury. Among these patients, 32 (76%) received appropriate cefepime dose adjustment. Three patients had a normal renal function at the time of CIN onset. The logistic regression model suggested that maintenance hemodialysis and longer duration of cefepime use were independently associated with the development of CIN, with odds ratios of 3.8 and 1.2, respectively. NCSE was frequently noted in the CIN patients (64%). Generalized periodic discharge with or without triphasic morphology was the most common EEG pattern (38%), followed by generalized rhythmic delta activity and generalized spike-and-waves. AEDs were administered to 86% of the patients. A total of 17 patients (40%) did not survive to hospital discharge. Adequate cefepime dose adjustment and early cefepime discontinuation led to a better prognosis.


CIN was associated with high mortality and morbidity rates. Neurotoxic symptoms could still occur when the cefepime dose was adjusted, or in patients with normal renal function. Patients with maintenance hemodialysis or a longer duration of cefepime therapy tended to develop CIN. Early recognition of abnormal EEG findings allowed for the withdrawal of the offending agent, resulting in clinical improvements and a better prognosis at discharge.


Cefepime neurotoxicity Encephalopathy Periodic discharges Prognostic factor Hemodialysis 


Author’s contribution

HL contributed to the design, analysis, and interpretation of the data, and drafting of the manuscript for intellectual content. CL contributed to the design and analysis of the data, and revised the manuscript. TW contributed to the design and acquisition of the data. MC, WT, CC, HH, HC, CL, BC, and WL contributed to the interpretation of the data and statistical analysis. SL contributed to the design and conceptualization of the study, the analysis and interpretation of the data, and drafting, revising, and final approval of the manuscript for intellectual content.

Source of support

This work was supported by the Chang Gung Memorial Hospital, Taiwan (Grant Nos. CMRPG3F2301, CMRPG3C1121-3 and CMRPG3H0341) and the Ministry of Science and Technology, Taiwan (Grant Nos. NMRPG3E6101-2 and NMRPG3G0231).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics Approval and Consent to Participate

This retrospective study was conducted according to the regulations of the institutional review board of the Chang Gung Medical Foundation (201801183B0C601). The ethics committees approved the study protocol and waived the need for informed consent because this observational study did not modify the physician’s treatment decisions, and patients’ anonymity was guaranteed.

Supplementary material

12028_2019_682_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2019

Authors and Affiliations

  • Han-Tao Li
    • 1
  • Chih-Hong Lee
    • 1
  • Tony Wu
    • 1
  • Mei-Yun Cheng
    • 1
  • Wei-En Johnny Tseng
    • 1
  • Chun-Wei Chang
    • 1
  • Hsiang-Yao Hsieh
    • 1
  • Hsing-I Chiang
    • 1
  • Chih-Yin Lin
    • 1
  • Bao-Luen Chang
    • 1
  • Wey-Ran Lin
    • 2
  • Siew-Na Lim
    • 1
    Email author
  1. 1.Section of Epilepsy, Department of NeurologyChang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of MedicineTaoyuanTaiwan
  2. 2.Department of Gastroenterology and HepatologyChang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of MedicineTaoyuanTaiwan

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