title: Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg.
abstract: To cover intermediate sensitive Candida glabrata in ICU patients, fluconazole plasma peak levels at least in the range of 16-32 microg/ml appear necessary for treatment. Previous studies did not reach these fluconazole levels under continuous veno-venous haemofiltration (CVVHF) with dosages of 200-600 mg fluconzole daily. In the present study, nine patients simultaneously requiring CVVHF for treatment of acute oligoanuric renal failure and antimycotic therapy of Candida septicemia received fluconazole 800 mg/day. Fluconazole plasma levels were determined to evaluate whether this dosage is adequate to reach the advised fluconazole levels. Patients were dialysed on two consecutive days with an ultrafiltration rate (UF) of 1000 ml/h or 2000 ml/h, respectively, in a randomized order. The predilution was 800 ml/h and 1800 ml/h, respectively. The treatment was tolerated without adverse effects. All patients reached plasma fluconazole concentrations between 16 and 32 microg/ml, remaining in this range for a minimum of 1 up to 24 h with a mean of 9.6 h and a UF rate of 2000 ml/h, and 15.7 h with a UF rate of 1000 ml/h. So far, there are no in vivo data on the fluconazole plasma concentrations required for effective treatment. However, our data demonstrate, that at least the fluconazole concentrations desirable on the basis of in vitro susceptibility testing can be reached in critically ill patients on CVVHF in an ICU setting. However, in these patients, 800 mg fluconazole/day are necessary to achieve fungicidal drug concentrations.
authors.affiliation: Medical Department A, Klinikum der Stadt Ludwigshafen, 67063 Ludwigshafen, Germany. bergnerr@klilu.de
authors.forename: Raoul
authors.initials: R
authors.lastname: Bergner
authors.forename: Martin
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Riedel
authors.forename: Gerd
authors.initials: G
authors.lastname: Mikus
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Henrich
authors.forename: Walter E
authors.initials: WE
authors.lastname: Haefeli
authors.forename: Michael
authors.initials: M
authors.lastname: Uppenkamp
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Walter-Sack
mesh_terms: D058186:Acute Kidney Injury / Q000382:microbiology / Q000628:therapy; D000935:Antifungal Agents / Q000008:administration & dosage*; D041221:Candida glabrata / Q000472:pathogenicity; D002177:Candidiasis / Q000628:therapy; D003430:Cross-Sectional Studies; D015725:Fluconazole / Q000008:administration & dosage*; D006440:Hemofiltration; D006801:Humans; D011446:Prospective Studies; D006435:Renal Dialysis
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole