Neurotoxicity by Cefepime: Case-Control Study

Abstract

Background: Cefepime is a fourth-generation cephalosporin widely used for empiric treatment of severe infections. Neurotoxicity by cefepime have been reported due to γ-aminobutyric acid A receptor inhibition or other mechanisms. The aim of this study was to evaluate the risk factors for cefepime-induced neurotoxicity between group showing cefepime-induced neurotoxicity and group without neurotoxicity. Methods: From Jan 2005 to June 2010, a total of 2,461 patients (older than 20) who used cefepime were considered in this study. We compared patients who developed cefepime-induced neurotoxicity (patient group, n=21) to patients who had no cefepime-induced neurotoxicity (control group, n=31). We analyzed demographic, underlying diseases, and metabolic parameters before cefepime treatment and during cefepime treatment between the two groups. Statistical analysis was performed using SPSS 18 software. Results: Of the total 2461 patients, 21 (0.85%) were diagnosed with cefepime-induced neurotoxicity. Impaired glomerular filtration rate (GFR at 15-30 ml/min) before cefepime use were significantly (P <0.05) higher risk for developing cefepime-induced neurotoxicity in patient group compared to that in the control group. Age, sex, and other metabolic parameters except GFR before and during, usage of cefepime did not show any statistical difference between the two groups. Conclusion: The present study revealed that cefepime-induced neurotoxicity was prone to develop in patients with impaired renal function before cefepime usage.

Cefepime-induced neurotoxicity

“…Incidence in critically ill patients [6] and in patients with hematologic malignancies [24] was 15% and 4.1%. The incidence of CIN in a retrospective case-control study in Korean patients was 0.85% [25]. The incidence in ESRD patients was 7.5%, but was 22.2% in ESRD patients with preexisting CNS morbidity [17].…”

Cefepime-Induced Encephalopathy in a Tertiary Medical Center in Korea

“…This study found that decreased eGFR was the most-significant risk factor for CIE. We showed that lower eGFR levels and dialysis were related to a higher incidence of CIE. We further found that 63.6% of the CIE patients had an eGFR of below 60 mL/min/1.73 mm 2 , which is similar to previous studies. 8 Among patients with reduced renal function who do not receive dialysis, the incidence of CIE was highest when eGFR was above 11 mL/min/1.73 mm 2 and below 30 mL/min/1.73 mm 2 . Further studies are needed to explain whether the physician had followed the dosing standard according to the eGFR of each patient, and what the serum level of cefepime was for each patient.…”

“…Fugate et al 9 found that 7 of 100 patients in an intensive care unit (ICU) setting had definite CIE. In Korea, Kang and Kim 8 reported that 21 (0.85%) of 2,461 patients were diagnosed with CIE. This wide range of the reported incidence rates may be expected given both the heterogeneity in diagnostic criteria for CIE and the diversity of the populations analyzed in these studies.…”

“…The present study was subject to a few limitations. Unlike previous studies, 8 we did not include EEG findings in the diagnostic criteria for CIE due to the retrospective design of this study. This might have reduced the specificity of the CIE diagnoses.…”

“…The reported incidence of CIE has ranged from 0.2% to 7.0%. 2 7 8 9 Appa et al 2 reported an incidence at their center of 1 (0.2%) in 480 courses of cefepime. Naeije et al 7 reported that 14 (1.25%) out of 1,120 patients who received cefepime showed continuous or intermittent generalized periodic epileptiform discharges.…”