Bergner R et al. (2006) Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg. Nephrol Dial Transplant 21: 1019–1023

Fungal septicemia caused by Candida spp. is treated with fluconazole. In vitro testing of the effects of fluconazole on Candida spp. indicated that plasma levels of 16–32 µg/ml are necessary to inhibit growth of some Candida spp. effectively. In patients receiving continuous veno-venous hemofiltration or continuous veno-venous hemodialysis, trials of fluconazole infusions of 200–600 mg/day failed to reach the required plasma concentration. Researchers in Germany attempted to determine whether a fluconazole dose of 800 mg/day would produce the required plasma concentration in nine intensive-care patients receiving continuous veno-venous hemofiltration for acute renal failure.

Dialysis was carried out in two consecutive 24 h periods with an ultrafiltration rate of 1,000 ml/h on one day and a rate of 2,000 ml/h on the other, in a randomized order, with predilution of 800 ml/h and 1,800 ml/h, respectively. Peak fluconazole concentrations of 16–32 µg/ml were reached in all patients. Mean concentrations above 16 µg/ml were maintained for 17.0 ± 8.0 h at an ultrafiltration rate of 1,000 ml/h, and for 9.1 ± 8.3 h at an ultrafiltration rate of 2,000 ml/h. The treatment was well tolerated.

Although the in vivo concentration of fluconazole necessary for a therapeutic effect is not yet known, the study demonstrates that concentrations known to be effective against Candida spp. in vitro can be reached without adverse effects in critically ill patients.