AMPHOTERICIN-B REFRACTORY ASPERGILLOSIS AFTER ITRACONAZOLE - EVIDENCEFOR SIGNIFICANT ANTAGONISM

Failure of amphotericin B to halt aspergillosis in a patient previousl y treated with itraconazole raised the question of whether amphoterici n B lost its activity as a result of antagonism between the two antifu ngal drugs. Azoles exhaust the target of amphotericin B on the fungal cell membrane. Accordingly amphotericin B in vitro lost its activity a gainst six isolates of Aspergillus fumigatus after exposure to subfung icidal concentrations of itraconazole. Prior treatment of mice with it raconazole abolished the protective effect of amphotericin B, even whe n itraconazole was stopped before starting amphotericin B therapy. The se observations raise concern about sequential therapy of aspergillosi s with itraconazole followed by amphotericin B.