Giuseppe
Emeritus
[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
-------
Evaluation of in vitro activity of voriconazole as predictive of in vivo outcome in a murine Aspergillus fumigatus infection model
Valentina Salas 1, F. Javier Pastor 1, Enrique Calvo 1, Deanna A. Sutton 3, Anette W. Fothergill 3 and Josep Guarro 1
Author Affiliations: <SUP>1</SUP>Unitat de Microbiologia, Facultat de Medicina i Ci?ncies de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Spain <SUP>3</SUP>Fungus Testing Laboratory University of Texas Health Science Center, San Antonio, Texas
ABSTRACT
We have evaluated the in vitro activity of voriconazole against 61 strains of Aspergillus fumigatus by using broth microdilution, disk diffusion, and minimal fungicidal concentration procedures. We observed an excellent correlation between the results obtained with the three methods. Five percent of the strains showed MICs ≥ epidemiological cut-off value (ECV = 1 μg/ml). To assess if MICs were predictive of in vivo outcome, we tested the efficacy of voriconazole at 25 mg/kg daily in an immunosuppressed murine model of disseminated infection using ten strains representing various susceptibility patterns to the drug as determined by the in vitro study. Voriconazole prolonged survival and reduced fungal load in the kidneys and brain in those mice infected with strains with MICs ≤ 0.25 μg/ml, while in that with MICs of 0.5 ? 2 μg/ml, the efficacy was variable and strain dependent, and in mice infected with the strain with MIC of 4 μg/ml the antifungal did not show efficacy Voriconazole reduced galactomannan antigenemia against practically all strains with an MIC < 4 μg/ml. Our results demonstrate that some relationship exists between voriconazole MICs and in vivo efficacy; however, further studies testing additional strains are needed to better ascertain which MIC values can predict clinical outcome.
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
-Valentina Salas 1, F. Javier Pastor 1, Enrique Calvo 1, Deanna A. Sutton 3, Anette W. Fothergill 3 and Josep Guarro 1
Author Affiliations: <SUP>1</SUP>Unitat de Microbiologia, Facultat de Medicina i Ci?ncies de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Spain <SUP>3</SUP>Fungus Testing Laboratory University of Texas Health Science Center, San Antonio, Texas
ABSTRACT
We have evaluated the in vitro activity of voriconazole against 61 strains of Aspergillus fumigatus by using broth microdilution, disk diffusion, and minimal fungicidal concentration procedures. We observed an excellent correlation between the results obtained with the three methods. Five percent of the strains showed MICs ≥ epidemiological cut-off value (ECV = 1 μg/ml). To assess if MICs were predictive of in vivo outcome, we tested the efficacy of voriconazole at 25 mg/kg daily in an immunosuppressed murine model of disseminated infection using ten strains representing various susceptibility patterns to the drug as determined by the in vitro study. Voriconazole prolonged survival and reduced fungal load in the kidneys and brain in those mice infected with strains with MICs ≤ 0.25 μg/ml, while in that with MICs of 0.5 ? 2 μg/ml, the efficacy was variable and strain dependent, and in mice infected with the strain with MIC of 4 μg/ml the antifungal did not show efficacy Voriconazole reduced galactomannan antigenemia against practically all strains with an MIC < 4 μg/ml. Our results demonstrate that some relationship exists between voriconazole MICs and in vivo efficacy; however, further studies testing additional strains are needed to better ascertain which MIC values can predict clinical outcome.
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
-------