Clinical Efficacy of Itraconazole for Systemic Aspergillosis: Multicentre Study in Japan

Abstract

A multicentre clinical trial of itraconazole for systemic mycoses was carried out in 25 hospitals in Japan. The clinical efficacy and safety of itraconazole in 41 cases of systemic aspergillosis are reported here. Of the patients, 9 were diagnosed as having bronchopulmonary aspergillosis, 30 had pulmonary aspergilloma, 1 had chronic necrotizing pulmonary aspergillosis and 1 had pleural aspergillosis. The diagnosis was established by microscopy, culture, histology, serology, biopsy, radiography and/or endoscopy. The mean age of the patients was 59.0 &#177; 14.5 years (range, 11-88 years). Itraconazole, 50-200 mg/day, was given for a mean of 150.5 days. Eradication of the fungus was observed in 17 patients out of the 22 cases examined mycologically. The overall clinical efficacy (cure or improvement) was 88.9% (8/9) in bronchopulmonary aspergillosis and 83.3% (25/30) in pulmonary aspergilloma, determined by clinical symptoms, mycological effects and radiographic observation. Radiographic evidence of the disappearance or improvement in size of the fungal ball was observed in 10 patients (33.3%) with aspergilloma. Itraconazole was clinically well tolerated; only 1 patient had pruritus, 1 had constipation, and in 1 elevation of serum aspartate aminotransferase, serum alanine aminotransferase and serum alkaline phosphatase was observed. The minimum inhibitory concentration (MIC) of itraconazole for isolates of <i>Aspergillus </i>from 9/13 cases was below 0.08 &#181;g/ml. As only a few antifungal agents show any activity against <i>Aspergillus </i>spp., itraconazole was considered to be a useful oral agent for treatment of systemic aspergillosis, including pulmonary aspergilloma.