title: Relationship between PK/PD of Cefepime and Clinical Outcome in Febrile Neutropenic Patients with Normal Renal Function.
abstract: The efficacy of cefepime (CFPM) is known to depend on the ratio of the time that the serum levels exceed the minimum inhibitory concentration (MIC) to the dosing interval (%T>MIC). The objective of this study was to clarify the relation between %T>MIC and clinical outcome of CFPM, and to identify the optimal dosage regimen. We investigated the outcome of CFPM treatment for febrile neutropenia (FN) patients with normal renal function. Treatment success was defined as the completion of FN therapy with CFPM only. And we calculated %T>MIC for each case based on population pharmacokinetic parameters. The MIC value for simulation was set as 8 μg/mL. In logistic regression analysis, treatment success was significantly associated with the elevation of %T>MIC in the group with persistent neutropenia, yielding a receiver operating characteristic curve with an optimal cutoff value of 73.1%. Next, we simulated %T>MIC for each case under various dosing regimens. For patients whose creatinine clearance (CLcr) exceeded 100 mL/min, it was found to be difficult to attain the objective under the current regimen. In contrast, it was calculated that treatment with 2 g three times a day (t.i.d.) could attain the objective for most of the patients with 3 h of infusion. These results suggest that CFPM treatment under the current regimen is ineffective for FN patients with normal or augmented renal function, and that 2 g t.i.d. is necessary in quite a lot cases, although such use is off-label.
authors.affiliation: Department of Pharmacy, Sapporo City General Hospital.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kamiyama
authors.forename: Asuka
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kanoh
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yuhki
authors.forename: Akira
authors.initials: A
authors.lastname: Ueda
authors.forename: Yukari
authors.initials: Y
authors.lastname: Kawamoto
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Gotoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003404:Creatinine; D004305:Dose-Response Relationship, Drug; D064147:Febrile Neutropenia / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime; D003404:Creatinine