title: Voriconazole MICs are predictive for the outcome of experimental disseminated scedosporiosis.
abstract: Scedosporiosis is associated with a mortality rate of up to 90% in patients suffering from disseminated infections. Recommended first-line treatment is voriconazole, but epidemiological cut-off values and clinical breakpoints have not been determined.
  
  
  
  To correlate voriconazole treatment response in mice suffering from disseminated scedosporiosis with MIC values determined using CLSI broth microdilution, Etest (bioMérieux) and disc diffusion.
  
  
  
  Voriconazole MICs for 31 Scedosporium apiospermum strains were determined using CLSI broth microdilution, Etest and disc diffusion. Groups of mice were challenged intravenously with 1 out of 16 S. apiospermum strains (voriconazole CLSI broth microdilution MIC range: 0.125-8.0 mg/L) and treated with 40 mg/kg voriconazole orally by gavage once daily. Efficacy of voriconazole was evaluated by a statistically significant ( P  <   0.05) reduction in fungal burden in brain.
  
  
  
  A categorical agreement of 90.4% was reached for CLSI broth microdilution and disc diffusion and of 93.6% for CLSI broth microdilution and Etest. Correlation of CLSI MICs and in vivo outcome was good, as mice challenged with strains with an MIC ≤2 mg/L responded to voriconazole therapy in 92.3% and those challenged with strains with an MIC ≥4 mg/L responded to voriconazole therapy in 33.3%.
  
  
  
  CLSI broth microdilution and Etest deliver comparable results that enable a prediction of in vivo outcome. Our results suggest that voriconazole is able to reduce fungal burden in the brain of 92.3% of all mice challenged with strains with voriconazole CLSI MICs ≤2 mg/L, while mice challenged with strains with CLSI MICs ≥4 mg/L showed limited response to voriconazole treatment.
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: Martin-Vicente
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Guarro
authors.affiliation: Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
authors.forename: Gloria M
authors.initials: GM
authors.lastname: González
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Lackner
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Capilla
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000382:microbiology; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D011237:Predictive Value of Tests; D021681:Scedosporium / Q000187:drug effects*; D065819:Voriconazole / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole