NEW YORK (Reuters Health) – Patients with febrile neutropenia on high doses of cefepime may be at risk for neurological toxicity, according to a study published online July 12th in Antimicrobial Agents and Chemotherapy.

Close monitoring of their kidney function is essential, the authors say. The patients in their study who developed neurological toxicity had no more than mild renal impairment when symptoms began — a finding that challenges previous reports that neurological toxicity is often limited to patients with severe kidney dysfunction.

But when plasma trough concentrations were measured, patients with neurological toxicity were receiving significantly higher median cefepime doses per 100 mL/min of glomerular filtration rate (GFR): 13.2 g/day, vs 7.1 g/day in patients with normal neurological function.

Led by Dr. Frederic Lamoth of Centre Hospitalier Universitaire Vaudois and the University of Lausanne in Switzerland, the authors reviewed the medical records of 30 patients with febrile neutropenia who had documented cefepime trough concentrations. Each was receiving 6 g/day of cefepime, except for those who had dosage adjustments based on their GFR.

Eight of the 30 patients developed neurological symptoms, including six whose symptoms were consistent with cefepime-associated neurological toxicity. In these patients, symptoms began an average of 3 days after they started on the antibiotic. An average of 4 days after the start of therapy, their median cefepime trough concentration was 28 mg/L, significantly higher than the 7.2 mg/L in patients with no neurological symptoms (p < 0.0001).

Cefepime trough concentrations were independently associated with neurological symptoms, with a 50% probability threshold for neurological toxicity at 22 mg/L.

All 6 patients with cefepime-associated neurological toxicity had only mild renal impairment. While they initially met the requirements for normal cefepime dosing (median baseline GFR = 57 ml/min), GFR had decreased below the threshold for renal dose adjustments (50 mL/min) in 4 out of 6 cases