Voriconazole MICs are predictive for the outcome of experimental disseminated scedosporiosis
Voriconazole MICs are predictive for the outcome of experimental disseminated scedosporiosis
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DOI:
10.1093/jac/dkw532
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发表时间:
2017-04-01
影响因子:
5.2
通讯作者:
Capilla, Javier
中科院分区:
文献类型:
--
作者:
Martin-Vicente, Adela;Guarro, Josep;Capilla, Javier
Background: 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.Objectives: To correlate voriconazole treatment response in mice suffering from disseminated scedosporiosis with MIC values determined using CLSI broth microdilution, Etest (bioMerieux) and disc diffusion.Methods: 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.Results: 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 = 4 mg/L responded to voriconazole therapy in 33.3%.Conclusions: 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 = 4 mg/L showed limited response to voriconazole treatment.