PT - JOURNAL ARTICLE AU - Veena Venugopalan AU - Cara Nys AU - Natalie Hurst AU - Yiqing Chen AU - Maria Bruzzone AU - Kartikeya Cherabuddi AU - Nicole Iovine AU - Jiajun Liu AU - Mohammad H. Al-Shaer AU - Marc H. Scheetz AU - Nathaniel Rhodes AU - Charles A. Peloquin AU - Kenneth Klinker TI - Use of Therapeutic Drug Monitoring to Characterize Cefepime-Induced Neurotoxicity AID - 10.1101/2020.08.13.250456 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.08.13.250456 4099 - http://biorxiv.org/content/early/2020/08/14/2020.08.13.250456.short 4100 - http://biorxiv.org/content/early/2020/08/14/2020.08.13.250456.full AB - Background The incidence of cefepime-induced neurotoxicity (CIN) in hospitalized patients is highly variable. Although greater cefepime exposures incite neurotoxicity, data evaluating trough thresholds associated with CIN remains limited. The objectives of this study were to evaluate the incidence of CIN, assess the relationship between cefepime trough concentrations and CIN, investigate clinical factors associated with CIN, and describe electroencephalogram (EEG) abnormalities in CIN.Methods This was a retrospective study of adult patients who had received ≥ 5 days of cefepime with ≥ 1 trough concentration > 25 mg/L. Potential CIN cases were identified utilizing neurological symptoms, neurologist assessments, EEG findings and improvement of neurotoxicity after cefepime discontinuation.Results One-hundred and forty-two patients were included. The incidence of CIN was 13% (18/142). The mean cefepime trough concentration in CIN patients was significantly greater than the non-neurotoxicity group (74.2 mg/L ± 41.1 vs. 46.6 mg/L ± 23, p=0.015). Lower renal function (creatinine clearance < 30 ml/min), greater time to therapeutic drug monitoring (TDM) (≥72 hours), and each 1 mg/mL rise in cefepime trough were independently associated with increased risk of CIN. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CIN.Conclusion Cefepime should be used cautiously in hospitalized patients due to the risk of neurotoxicity. Patients with greater renal function and those who had early cefepime TDM (≤ 72 hours) had lower risk of CIN.