Posaconazole Prophylaxis in Experimental Azole-Resistant Invasive Pulmonary Aspergillosis

Seyed Seyed Mousavi Tasieh, Johan Mouton, WJG Melchers, PE Verweij

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Abstract

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. fumigatus with 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.
Original languageUndefined/Unknown
Pages (from-to)1487-1494
Number of pages8
JournalAntimicrobial Agents & Chemotherapy
Volume59
Issue number3
DOIs
Publication statusPublished - 2015

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