Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole

This study analyses invasive fungal infections in neutropenic patients with haematological malignancies during antifungal prophylaxis with itraconazol e. From September 1994 to December 1998 20 patients developed fungal infect ions. Two patients suffered from disseminated infections by yeasts and 18 p atients suffered from pulmonary infections by moulds (eight proven, 10 high ly probable in high-resolution CT scans). In these patients the itraconazol e trough concentrations exceeded 500 ng ml(-1) (measured by high performanc e liquid chromatography) significantly less often (median 48%, interquartil e range 0-100%) than in another group of 150 leukaemia patients without inv asive fungal infections who received 287 courses of prophylaxis with itraco nazole at our institution (median 100%, interquartile range 38-100%, P=0.03 9). Twelve patients died, six of these had refractory disease. Patients wit h fatal invasive fungal infections had lower median itraconazole concentrat ions immediately before occurrence of the infection than patients with non- fatal infections: 120 (0-478) ng ml(-1) versus 690 (305-1908) ng ml(-1) (P= 0.039). In conclusion, this analysis of breakthrough invasive fungal infect ions during prophylaxis with itraconazole demonstrates that patients with i traconazole trough concentrations below 500 ng ml(-1) were significantly mo re likely to develop fungal infections and that the last itraconazole troug h concentration before occurrence of the infection was significantly lower in patients with fatal invasive fungal infections.