Cefepime-induced encephalopathy in patients with haematological malignancies: clinical features and risk factors

Cefepime is an antibiotic that is widely used in patients with haematological malignancies (HM). Although its use has been reported to be associated with encephalopathy, only case reports or small case series have been reported so far.

We conducted a retrospective cohort study of 243 patients with HM treated with cefepime at our hospital between August 2011 and May 2013. We also investigated the clinical features of patients with cefepime-induced encephalopathy (CIE).

Among 243 HM patients treated with cefepime, 10 were diagnosed with CIE, indicating a cumulative incidence of approximately 4.1%. The median creatinine level on commencement of treatment was 2.13 mg/dl (range 0.60-19.85) and the median initial dose of cefepime was 4.0 g/day (range 1.0-6.0). The median time between commencement of treatment and symptoms was 4.0 days (range 2-5). The most common clinical manifestations were decreased level of consciousness and myoclonus. Symptoms resolved fully in all patients. Univariate analyses showed that impaired renal function (creatinine clearance (CLCr) < 30 ml/min, acute renal failure, and chronic dialysis) was significantly associated with the development of CIE (univariate p < 0.0001, p = 0.020, and p = 0.0025, respectively). Receiver operating characteristic (ROC) analysis demonstrated that the threshold levels of creatinine, CLCr, and estimated glomerular filtration rate for CIE were 1.22 mg/dl, 22.96 ml/min, and 43.9 ml/min/1.73 m(2), respectively.

This study indicated that the development of CIE is associated with severely impaired renal function in patients with HM.