title: Posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis.
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.
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Seyedmojtaba
authors.identifier: http://orcid.org/0000-0002-6194-7447
authors.initials: S
authors.lastname: Seyedmousavi
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Johan W
authors.identifier: http://orcid.org/0000-0001-6736-4149
authors.initials: JW
authors.lastname: Mouton
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Willem J G
authors.initials: WJ
authors.lastname: Melchers
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands Paul.Verweij@radboudumc.nl.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001232:Aspergillus fumigatus / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal; D005260:Female; D055744:Invasive Pulmonary Aspergillosis / Q000517:prevention & control*; D051379:Mice; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole