Amphotericin B refractory aspergillosis after itraconazole: evidence for significant antagonism.
Failure of amphotericin B to halt aspergillosis in a patient previously treated with itraconazole raised the question of whether amphotericin B lost its activity as a result of antagonism between the two antifungal drugs. Azoles exhaust the target of amphotericin B on the fungal cell membrane. Accordingly amphotericin B in vitro lost its activity against six isolates of Aspergillus fumigatus after exposure to subfungicidal concentrations of itraconazole. Prior treatment of mice with itraconazole abolished the protective effect of amphotericin B, even when itraconazole was stopped before starting amphotericin B therapy. These observations raise concern about sequential therapy of aspergillosis with itraconazole followed by amphotericin B.
Schaffner
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Department of Medicine, University of Zürich Medical School, Switzerland.
Böhler
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D000666:Amphotericin B / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000818:Animals; D001228:Aspergillosis / Q000188:drug therapy* / Q000209:etiology; D001232:Aspergillus fumigatus / Q000187:drug effects*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged; D009894:Opportunistic Infections / Q000188:drug therapy* / Q000209:etiology
D017964:Itraconazole; D000666:Amphotericin B