Itraconazole in Systemic Aspergillosis: Experience in 22 Cases

Abstract

The results obtained in an open, retrospective, multicentre study of itraconazole in monotherapy are reported here. Itraconazole was supplied to several physicians to treat patients suffering from systemic aspergillosis on a compassionate-use basis. Diagnosis of aspergillosis was based on clinical, mycological, serological and/or radiological data. Nine cases occurred in patients with cystic fibrosis (ages, 6-24 years), among whom 8 cases were diagnosed as allergic bronchopulmonary aspergillosis and 1 as chronic necrotizing aspergillosis. Six patients were immunocompromised (ages, 35-83 years; including 3 with leukaemia, 1 liver transplant patient, 1 heart transplant patient and 1 patient with acquired immune deficiency syndrome (AIDS)), with invasive aspergillosis involving lungs (4 patients), sinuses (1 patient) and bronchi (1 patient). Another 7 patients were diagnosed as having chronic necrotizing aspergillosis (ages, 29-81 years). Immunocompromised patients were treated with itraconazole, 400 mg/day (median dose; range, 200-600 mg/day). Other patients were treated with 200 mg daily. Due to poor absorption in patients with cystic fibrosis, the recommended initial dose of itraconazole was 10 mg/kg/day. During therapy, this dose was adapted according to the measured plasma levels of itraconazole. None of the patients received prior or concomitant amphotericin B. The mean duration of treatment was 179 days (range, 90-375 days) in invasive aspergillosis, 97 days (range, 10-240 days) in chronic necrotizing aspergillosis and 320 days (range, 15-750 days) in aspergillosis in patients with cystic fibrosis. The overall results were good in 19 cases; 8 were cured, 9 improved markedly and 2 improved moderately. One case was unchanged and 1 case failed; 1 patient was unevaluable. Of the patients with invasive aspergillosis, 4 were cured, 1 improved and 1 was unevaluable. Of the patients with chronic necrotizing aspergillosis, 1 was cured, 5 improved and 1 was stable. Of the patients with cystic fibrosis, 3 were cured, 4 improved markedly, 1 improved moderately and 1 failed. Follow-up data after stopping itraconazole were available in 18 cases (mean duration 8 months; range, 1-27 months). Four patients died due to underlying disease, 1 case relapsed 18 months after stopping treatment, 1 case was unchanged and all other cases remained cured (11) or improved further (1). Tolerance data were available for 12 patients, of whom 10 tolerated itraconazole well and 2 suffered drowsiness or gastric intolerance.