Adequacy of High-Dose Cefepime Regimen in Febrile Neutropenic Patients with Hematological Malignancies

While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been con-troversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the con-sequent 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 theMIC (fT>MIC). Target attainment was assessed in reference to theMIC 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 concentration