title: Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies.
abstract: While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been controversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the consequent suboptimal exposure call for a pharmacokinetic/pharmacodynamic evaluation of current dosing. This study aimed to assess pharmacokinetic/pharmacodynamic target attainment from a 2-g intravenous (i.v.) every 8 h (q8h) cefepime regimen in febrile neutropenic patients with hematological malignancies. Cefepime plasma concentrations were measured in the 3rd, 6th, and 9th dosing intervals at 60% of the interval and/or trough point. The selected pharmacokinetic/pharmacodynamic targets were the proportion of the dosing interval (60% and 100%) for which the free drug concentration remains above the MIC (fT>MIC). Target attainment was assessed in reference to the MIC of isolated organisms if available or empirical breakpoints if not. The percentage of fT>MIC was also estimated by log-linear regression analysis. All patients achieved >60% fT>MIC in the 3rd and 6th dosing intervals. A 100% fT>MIC was not attained in 6/12, 4/10, and 4/9 patients in the 3rd, 6th, and 9th dose intervals, respectively, or in 14/31 (45%) of the dosing intervals investigated. On the other hand, 29/31 (94%) of trough concentrations were at or above 4 mg/liter. In conclusion, for patients with normal renal function, a high-dose 2-g i.v. q8h cefepime regimen appears to provide appropriate exposure if the MIC of the organism is ≤4 mg/liter but may fail to cover less susceptible organisms.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia Fekade.Sime@mymail.unisa.edu.au.
authors.forename: Fekade Bruck
authors.initials: FB
authors.lastname: Sime
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia Therapeutics Research Centre, School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.affiliation: Department of Haematology/Oncology, The Queen Elizabeth Hospital, Adelaide, Australia SA Pathology and the University of Adelaide, Adelaide, Australia.
authors.forename: Ing Soo
authors.initials: IS
authors.lastname: Tiong
authors.affiliation: Department of Haematology/Oncology, The Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: Julia H
authors.initials: JH
authors.lastname: Gardner
authors.affiliation: Department of Haematology/Oncology, The Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: Sheila
authors.initials: S
authors.lastname: Lehman
authors.affiliation: Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Peake
authors.affiliation: Department of Haematology/Oncology, The Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: Uwe
authors.initials: U
authors.lastname: Hahn
authors.affiliation: SA Pathology and the University of Adelaide, Adelaide, Australia.
authors.forename: Morgyn S
authors.initials: MS
authors.lastname: Warner
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia Royal Brisbane and Women's Hospital, Herston, Brisbane, Australia Burns, Trauma, and Critical Care Research Centre, University of Queensland, Herston, Brisbane, Australia Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D064147:Febrile Neutropenia / Q000097:blood / Q000188:drug therapy; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime