title: In vivo efficacy of voriconazole and posaconazole therapy in a novel invertebrate model of Aspergillus fumigatus infection.
abstract: The emergence of azole resistance in Aspergillus fumigatus is a clinically important issue in the management of invasive aspergillosis as it could limit therapeutic options. Accurate measurement of in vitro antifungal activity in terms of minimum inhibitory concentration (MIC) is considered of clinical relevance and often gives useful therapeutic information for physicians. However, the lack of in vitro-in vivo correlation is frequent and the observed in vitro phenotype does not always correlate with the in vivo response. In this regard, a wild-type strain and five A. fumigatus cyp51A mutated strains showing different azole susceptibility profiles were used to investigate whether the greater wax moth (Galleria mellonella) is an alternative model to assess the in vivo efficacy of voriconazole and posaconazole. Administration of both azoles improved the survival of larvae infected with susceptible strains. However, those larvae infected with resistant strains did not respond to treatment. The phenotype observed in vitro was found to correlate with the efficacy observed in vivo. Moreover, using this in vivo model, the pharmacodynamic target predicting therapeutic success (AUC(0-24)/MIC) was in the same range as previously described, allowing the use of the G. mellonella model to predict the azole susceptibility profile of A. fumigatus strains.
authors.affiliation: Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2, Majadahonda, 28220 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Forastiero
authors.affiliation: Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2, Majadahonda, 28220 Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Bernal-Martínez
authors.affiliation: Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2, Majadahonda, 28220 Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Mellado
authors.affiliation: Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2, Majadahonda, 28220 Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Cendejas
authors.affiliation: Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2, Majadahonda, 28220 Madrid, Spain. Electronic address: aliciagl@isciii.es.
authors.forename: A
authors.initials: A
authors.lastname: Gomez-Lopez
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects*; D004195:Disease Models, Animal; D007814:Larva / Q000382:microbiology / Q000502:physiology; D007915:Lepidoptera; D008826:Microbial Sensitivity Tests; D016019:Survival Analysis; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D065819:Voriconazole
keywords: Aspergillus fumigatus cyp51A mutants; Azole exposure/efficacy; Galleria mellonella; Non-mammalian model