Acquired itraconazole resistance in Aspergillus fumigatus.
The antifungal susceptibility profiles of four ASPERGILLUS: fumigatus isolates, recovered at different times from a patient treated with itraconazole for a pulmonary ASPERGILLUS: infection, were evaluated. Itraconazole MICs against two pre-treatment isolates were 0.5 mg/L, whilst two later isolates, recovered after at least 4 months of itraconazole therapy, had itraconazole MICs of >16 mg/L. In vivo susceptibilities to itraconazole and amphotericin B were tested in a murine model of disseminated aspergillosis. Treatment efficacy was evaluated by examining mortality rates and qualitative cultures of brain and kidneys. Itraconazole therapy significantly prolonged survival of mice infected with the initial isolates as compared with untreated controls. The third isolate was only partially susceptible to itraconazole in vivo, and the fourth isolate was highly resistant. The four isolates were typed by random amplified polymorphic DNA (RAPD) with four different primers. RAPD patterns obtained with each of them were identical, suggesting that the same strain was recovered over time and had acquired resistance to itraconazole.
Laboratoire de Parasitologie, Mycologie Médicale et Pathologie Exotique, Université Claude Bernard Lyon I, 8 avenue Rockefeller, 69373 Lyon Cedex, France. edanna@rockefeller.univ-lyon1.fr
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Dannaoui
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Borel
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Monier
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Piens
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Picot
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Persat
D000368:Aged; D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D004271:DNA, Fungal / Q000235:genetics; D004352:Drug Resistance, Microbial; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology* / Q000627:therapeutic use; D008172:Lung Diseases, Fungal / Q000188:drug therapy; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D019105:Random Amplified Polymorphic DNA Technique; D016019:Survival Analysis
D000935:Antifungal Agents; D004271:DNA, Fungal; D017964:Itraconazole; D000666:Amphotericin B