Posaconazole Prophylaxis in Experimental Azole-Resistant Invasive Pulmonary Aspergillosis

We investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant Aspergillus fumigatus isolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazole MICs of 0.063 mg/liter (wild type), 0.5 mg/liter (F219I mutation), and 16 mg/ liter. A fourth isolate harboring TR34/L98H (MIC of 0.5 mg/liter) was also tested. Posaconazole prophylaxis was effective in A. fumigatuswith posaconazole MICs of<0.5 mg/liter, where 100 % survival was reached. However, breakthrough infection was observed in mice infected with the isolate for which the posaconazole MIC was>16 mg/liter. Invasive aspergillosis (IA) is an important opportunistic fungalinfection, especially among immunocompromised patients, with an overall mortality ranging between 30 and 88 % and up to 95 % in patients underlying azole-resistant Aspergillus fumigatus infections (1–5). Posaconazole (POS) is an extended-spectrum triazole recommended for salvage therapy and prophylaxis of aspergillus diseases in neutropenic patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and in pa-tients with graft-versus-host disease (GvHD) (6–8). The incidence of invasive fungal diseases is significantly reduced in patients re