Terbinafine in the treatment of non-immunocompromised compassionate cases of bronchopulmonary aspergillosis

Conventional treatments of bronchopulmonary aspergillosis are often ineffective and result in associated side-effects. Terbinafine (a new allylamine derivative), although as active against Aspergillus in vitro as amphotericin B and itraconazole, is less effective in rodent models because of a rapid hepatic first-pass effect. As terbinafine is metabolized differently in humans, the aim of this work was to evaluate this drug, for the first time, in the treatment of seven immunocompetent patients with lower respiratory tract mycotic infections unresponsive to the usual antimycotic drugs. Diagnosis was based on identification of fungal isolates, worsening of respiratory function tests, chest radiographs and computerized tomographic (CT) scan changes, positive skin test, aspergillin precipitins and clinical history. Terbinafine was administered at doses ranging from 5 to 15 mg kg-1 day-1 depending on the clinical severity of the disease, and was given for 90-270 days depending on clinical progress and compliance. In three patients A. fumigatus was suppressed with resolution of signs and symptoms; four patients showed transitory A. fumigatus suppression with marked clinical and radiological improvement. During relapses no resistance to terbinafine was observed. No significant side-effects were detected. Terbinafine appeared to be as effective as amphotericin B and itraconazole in the treatment of bronchopulmonary aspergillosis in nonimmunocompromised patients. These preliminary results suggest that controlled studies are warranted.