In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis

An animal model of disseminated aspergillosis was used to test the in-vivo activity of itraconazole against four isolates of Aspergillus fumigatus, Tw o reference isolates of A. fumigatus known to be resistant to itraconazole in vitro and in vivo were used as control isolates, and two new isolates we re tested under the same conditions. For each isolate MICs for itraconazole and amphotericin B were determined by an NCCLS-based method. Mice infected intravenously were treated either with itraconazole 100 mg/kg/day or ampho tericin B 4.5 mg/kg/day for 10 days. Amphotericin B showed good in-vivo act ivity against all four isolates, For one strain, which had a low in-vitro M IC for itraconazole, in-vivo therapy with itraconazole prolonged the surviv al of mice and reduced fungal burdens in organs compared with untreated con trols. In mice infected with a strain with a high MIC of >16 mg/L, itracona zole neither prolonged survival nor reduced fungal load in organs compared with controls. It is concluded that there is a relationship between MIC and treatment outcome in mice for A. fumigatus infection.