Extended infusion compared to standard infusion cefepime as empiric treatment of febrile neutropenia

Background: Extended infusion (EI) dosing provides a longer time above the minimum inhibitory concentration, which is important for the clinical success of beta-lactam antibiotics, especially for patients with impaired immunity. The aim of this study was to determine the feasibility and clinical impact of administering cefepime by EI as treatment of febrile neutropenia. Methods: This was a prospective, randomized, comparative pilot study. All patients received cefepime 2g IV every 8h, with the first dose administered using a 30-min infusion. After the first dose, patients were randomized to receive cefepime over 30min as a standard infusion (SI) or 3h (EI). Patients were >18 years old with febrile neutropenia (neutrophil count <500 cells/mm(3) and temperature >38.0 degrees C) and received chemotherapy or stem cell transplant as treatment for malignancy. Patients were excluded for the following: allergy to a cephalosporin, creatinine clearance (CrCl)<50mL/min, receipt of concurrent Gram-negative antimicrobial, sepsis, or solid tumor malignancy. The primary outcome was defervescence by 72h. Secondary outcomes included time to defervescence, clinical success, in-hospital mortality, hospital length of stay, and need for additional antimicrobials. Main results: Sixty-three patients were enrolled: 33 in the SI arm and 30 in the EI arm. The groups were similar with regard to age, gender, weight, estimated creatinine clearance, and duration of neutropenia. None of the patients in the EI arm withdrew due to practical complications of receiving EI cefepime. Twenty-three patients in the SI arm and 20 patients in the EI arm defervesced by 72h (p = 0.99). There were no differences in secondary outcome measures; however, patients in the EI arm appeared to have defervesced more rapidly (median 19 vs. 41h, p = 0.305). Conclusion: Administration of cefepime by EI for the treatment of febrile neutropenia is feasible. Larger clinical trials are necessary to determine if EI cefepime imparts a clinical benefit in the treatment of febrile neutropenia.