title: Evaluating outcomes of alternative dosing strategies for cefepime: a qualitative systematic review.
abstract: OBJECTIVE
  To perform a qualitative systematic review of the evidence comparing traditional with prolonged intermittent or continuous infusions of cefepime based on clinical and pharmacodynamic outcomes.
  
  
  METHODS
  PubMed (1946 to October 2014), EMBASE (1980 to October 2014), CENTRAL, Cochrane Database of Systematic Reviews, Web of Science, and International Pharmaceutical Abstracts (1970 to October 2014) were searched using the terms cefepime, pharmacokinetics, pharmacodynamics, drug administration, intravenous infusions, intravenous drug administration, continuous infusion, extended infusion, and intermittent therapy. Reference lists from relevant materials were reviewed.
  
  
  METHODS
  Articles evaluating administration regimens of cefepime, one of which included the traditional, manufacturer-recommended 0.5-hour infusion and the other a prolonged or continuous infusion were included. Prespecified clinical outcomes of interest included all-cause mortality, length of hospital stay, clinical cure, and adverse events. The primary pharmacodynamic outcome was percentage time of unbound drug concentration remaining above the minimum inhibitory concentration.
  
  
  RESULTS
  In all, 18 studies were included; 6 studies assessed clinical outcomes, and 12 assessed pharmacodynamic outcomes. Prolonged or continuous infusions of cefepime achieved the pharmacodynamic targets more often than traditional infusions. The association of improved clinical outcomes with prolonged or continuous infusions is unclear. All-cause mortality was significantly decreased with the use of a prolonged cefepime infusion in a retrospective study. Two prospective, randomized studies demonstrated no statistically significant difference in mortality between prolonged and intermittent infusions.
  
  
  CONCLUSIONS
  The available literature on prolonged and continuous infusions of cefepime demonstrated an improved achievement of pharmacodynamic targets; however, the effect on clinical outcomes is inconclusive. Well-designed prospective studies are required to determine optimal dosing and administration strategies.
authors.affiliation: University of British Columbia, Vancouver, BC, Canada.
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Burgess
authors.affiliation: Burnaby Hospital, BC, Canada Vincent.Mabasa@fraserhealth.ca.
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Mabasa
authors.affiliation: Burnaby Hospital, BC, Canada.
authors.forename: Ivy
authors.initials: I
authors.lastname: Chow
authors.affiliation: Children's and Women's Health Centre of British Columbia, Vancouver, BC, Canada.
authors.forename: Mary H H
authors.initials: MH
authors.lastname: Ensom
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001424:Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology*; D002423:Cause of Death; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D007902:Length of Stay / Q000706:statistics & numerical data; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime
keywords: cefepime; drug administration; infusion; pharmacodynamics; pharmacokinetics