title: Extended infusion compared to standard infusion cefepime as empiric treatment of febrile neutropenia.
abstract: Background Extended infusion (EI) dosing provides a longer time above the minimum inhibitory concentration, which is important for the clinical success of β-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 2 g IV every 8 h, with the first dose administered using a 30-min infusion. After the first dose, patients were randomized to receive cefepime over 30 min as a standard infusion (SI) or 3 h (EI). Patients were >18 years old with febrile neutropenia (neutrophil count <500 cells/mm3and temperature >38.0ºC) and received chemotherapy or stem cell transplant as treatment for malignancy. Patients were excluded for the following: allergy to a cephalosporin, creatinine clearance (CrCl) < 50 mL/min, receipt of concurrent Gram-negative antimicrobial, sepsis, or solid tumor malignancy. The primary outcome was defervescence by 72 h. 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 72 h ( 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. 41 h, 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.
authors.affiliation: 1 Department of Pharmacy, Duke University Hospital, Durham, NC, USA.
authors.forename: Rebekah H
authors.initials: RH
authors.lastname: Wrenn
authors.affiliation: 2 Department of Pharmacy Practice, ETSU Gatton College of Pharmacy, Johnson City, TN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cluck
authors.affiliation: 3 Department of Pharmacy, Wake Forest Baptist Health, Winston Salem, NC, USA.
authors.forename: LeAnne
authors.initials: L
authors.lastname: Kennedy
authors.affiliation: 4 Section on Infectious Diseases, Wake Forest Baptist Health, Winston Salem, NC, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ohl
authors.affiliation: 3 Department of Pharmacy, Wake Forest Baptist Health, Winston Salem, NC, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Williamson
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D036262:Empirical Research; D064147:Febrile Neutropenia / Q000188:drug therapy / Q000401:mortality; D017052:Hospital Mortality / Q000639:trends; D007262:Infusions, Intravenous; D010865:Pilot Projects; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000077723:Cefepime; D002511:Cephalosporins
keywords: Cefepime; extended infusion; neutropenic fever