Martin-Vicente Adela, Guarro Josep, González Gloria M, Lass-Flörl Cornelia, Lackner Michaela, Capilla Javier
Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
J Antimicrob Chemother. 2017 Apr 1;72(4):1118-1122. doi: 10.1093/jac/dkw532.
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.
播散性感染患者的足放线病菌病死亡率高达90%。推荐的一线治疗药物是伏立康唑，但尚未确定其流行病学截断值和临床断点。
将播散性足放线病菌病小鼠的伏立康唑治疗反应与采用CLSI肉汤微量稀释法、Etest（生物梅里埃公司）和纸片扩散法测定的MIC值相关联。
采用CLSI肉汤微量稀释法、Etest和纸片扩散法测定31株尖端赛多孢菌的伏立康唑MIC。将小鼠分为若干组，静脉注射16株尖端赛多孢菌中的1株（伏立康唑CLSI肉汤微量稀释法MIC范围：0.125 - 8.0mg/L），并通过灌胃每天口服一次40mg/kg伏立康唑进行治疗。通过脑内真菌负荷的统计学显著降低（P < 0.05）来评估伏立康唑的疗效。
CLSI肉汤微量稀释法与纸片扩散法的分类一致性为90.4%，CLSI肉汤微量稀释法与Etest的分类一致性为93.6%。CLSI MIC与体内结果的相关性良好，MIC≤2mg/L菌株攻击的小鼠中92.3%对伏立康唑治疗有反应，而MIC≥4mg/L菌株攻击的小鼠中33.3%对伏立康唑治疗有反应。
CLSI肉汤微量稀释法和Etest得出的结果相当，能够预测体内结果。我们的数据表明，伏立康唑能够降低92.3%的受伏立康唑CLSI MIC≤2mg/L菌株攻击的小鼠脑内真菌负荷，而受CLSI MIC≥4mg/L菌株攻击的小鼠对伏立康唑治疗反应有限。
