Refractory pulmonary aspergillosis: compassionate trial with terbinafine

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Abstract
The frequency of bronchopulmonary aspergillosis is increasing due to the growing number of patients requiring steroids or other immunosuppressive therapies. Conventional treatments are ineffective in some patients and side-effects are an important issue. The aim of this work was to evaluate the effectiveness and safety of terbinafine, a new allylamine antimycotic drug, in three immunocompetent patients affected by lower respiratory tract aspergillosis [one chronic empyema due to Aspergillus fumigatus (AF) and two chronic necrotising aspergillosis] not responsive to the usual antimycotic therapies. In in vitro and animal model systems, terbinafine is as active as amphotericin B and itraconazole. Patients received terbinafine at doses ranging from 5 to 15 mg/kg per day, according to clinical status, for 3-5 months, depending on the clinical course of the disease and compliance. In patient 1 a negative anti-AF precipitin was obtained together with eradication of AF from the pleural cavity, which allowed a successful intrathoracic myo-omento-mammoplasty. In patients 2 and 3, AF was eradicated, anti-AF immunoprecipitins decreased, and clinical and radiological findings significantly improved. On the basis of the effectiveness of terbinafine demonstrated in this preliminary work, large studies to evaluate the use of terbinafine in bronchopulmonary aspergillosis are warranted. Moreover, the drug is not associated with resistance or significant side-effects.