ANTIFUNGAL PROPHYLAXIS WITH ITRACONAZOLE IN NEUTROPENIC PATIENTS WITHACUTE-LEUKEMIA

The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treate d for acute leukaemia. A consecutive group of patients without systemi c antifungal prophylaxis (January 1993 to August 1994, period 1) was c ompared with another consecutive group of patients (period 2) who rece ived itraconazole capsules (September 1994 to April 1995 400 mg/day, f rom May 1995 onwards 600 mg/day). All patients admitted with acute leu kaemia and standard or high-dose chemotherapy were included into the s tudy. Clinical endpoint was mortality from proven fungal infection. Se venty-six patients and 148 courses of cytotoxic chemotherapy were anal ysed in the control group as well as 47 patients and 112 treatment cou rses in the intervention group. Antifungal prophylaxis led to a signif icant decrease of mortality from invasive fungal infections (8.8%-0.9% , P = 0.005). The median trough concentration of itraconazole of all m easurements was 520 ng/ml (range 230-793) in patients who received 400 mg/day and 760 ng/ml (370-1200) in patients receiving a dosage of 600 mg/day (P = 0.002). These findings suggest that itraconazole is an ef fective drug for antifungal prophylaxis but also that a considerable n umber of patients do not reach the desired trough levels (>500 ng/ml) with itraconazole capsules.