Continuous epileptiform discharges in patients treated with cefepime or meropenem

Arch Neurol. 2011 Oct;68(10):1303-7. doi: 10.1001/archneurol.2011.204.

Abstract

Objective: To test the hypothesis that treatment with cefepime hydrochloride leads to higher incidence of periodic epileptiform discharges compared with treatment with other β-lactams.

Design: Data from hospital pharmacy databases of patients treated with cefepime or meropenem during a 42-month period (from January 1, 2007, through June 30, 2010) were retrospectively crossed with data from the electroencephalography database for the same period.

Setting: Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Patients: Patients who underwent electroencephalographic testing while taking cefepime or meropenem were selected. Only electroencephalographic tests performed during the antibiotic treatment period were considered. Matches were compared with nurses' medication records to ensure that the antibiotic considered was effectively given.

Main outcome measure: Proportions of patients with continuous epileptiform discharges in the 2 groups were compared using the Fisher exact test.

Results: A total of 1120 patients were treated with cefepime and 1572 patients with meropenem. Electroencephalographic testing was performed during treatment in 59 patients treated with cefepime and 80 treated with meropenem (5.26% vs 5.08%, P = .85). Continuous epileptiform discharges were present in 14 patients in the cefepime group and 3 in the meropenem group (1.25% vs 0.19%, P < .001). Blood creatinine concentration was elevated in 5 of the 17 patients (range, 1.5-4.2 mg/dL; reference range, 0.7-1.2 mg/dL), and liver enzyme levels were elevated in 5 patients. No patient had major electrolyte disturbances.

Conclusions: Our study showed a prevalence of electroencephalographic test results with continuous epileptiform discharges in 14 of 1120 patients receiving cefepime (1.25%) but only 3 of 1572 patients receiving meropenem (0.19%). Contrary to the results of previous case series, these electroencephalographic patterns occurred, in most cases, in patients with normal renal function. These results suggest that cefepime may be an independent risk factor for periodic epileptiform discharges, which are associated with worse outcomes. This finding could provide a partial explanation for the higher mortality rates reported in patients treated with cefepime compared with other β-lactams.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Bacterial Infections / drug therapy
  • Belgium
  • Cefepime
  • Cephalosporins / adverse effects*
  • Cross-Over Studies
  • Electroencephalography
  • Epilepsy / chemically induced*
  • Epilepsy / physiopathology
  • Female
  • Humans
  • Male
  • Meropenem
  • Middle Aged
  • Pharmacy Service, Hospital / statistics & numerical data
  • Retrospective Studies
  • Thienamycins / adverse effects*

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Thienamycins
  • Cefepime
  • Meropenem