ObjectiveTo investigate antifungal activity in vitro of single or combination of triazole and echinocandin against Aspergillus species. MethodsBased on EUCAST protocol,the susceptibilities of 62 isolates of Aspergillus spp. were determined for voriconazole (VRC),itraconazole (ICZ),caspofungin (CAS) and micafungin (MICA). For VRC and ICZ,MIC-0 and MIC-2 were determined. For CAS and MICA,minimum effective concentration (MEC) and MIC-2 were determined. The fractional inhibitory concentration (FIC) was used to evaluate the effect of combination of triazole and echinocandin. ResultsIndifference was found in 2 isolates of Aspergillus fumigatus in combination of ICZ and CAS or MICA by using MIC-0 endpoint. Synergy was found in all other isolates of Aspergillus spp.With MIC-2 and MEC endpoints,synergy for VRC and CAS,VRC and MICA,ICZ and CAS and ICZ and MICA was found in 16,21,11 and 14 isolates of Aspergillus fumigatus,9,13,9 and 11 isolates of Aspergillus flavus,0,2,1 and 1 isolates of Aspergillus niger,respectively. ConclusionThe in vitro sensitivity results of combination of triazole and echinocandin are different with different endpoints. Thus,the efficacy of combination of triazole and echinocandin can not predicted by in vitro sensitivity and should be further confirmed in invasive aspergillosis animal experiments.
Objective To observe the effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at different doses. Methods According to the randomization table, 25 healthy rabbits were randomly divided into control group, and voriconazole 50, 100, 200, and 400 μg groups. Therefore, there were 5 rabbits in each group. The eyes of control group received intravitreal injection of 0.1 ml balanced saline solution, and those treatment groups received 0.1 ml voriconazole injection of corresponding dose. Before the injection and 1, 7, and 14 days after the injection, endothelial cell counts and corneal thicknesses were measured; full-field electroretinogram were performed and b-wave amplitudes in maximal combined reaction (Max-R) were recorded. On 14 days after the injection, histologic structures were observed by light microscope and transmission electron microscope. Results There was no significant difference in endothelial cell counts (F=0.320, 0.291, 0.467, 0.649) and corneal thicknesses (F=0.214, 0.284, 0.360, 0.225) with those of control group at any time points (P > 0.05). Before and 1 day after the injection, b-wave amplitudes of each voriconazole group had no significant difference compared with those of control group (F=0.220, 0.106; P > 0.05). On 7 days after the injection, b-wave amplitudes decreased significantly at doses of 200 μg and 400 μg (P < 0.05). On 14 days after the injection, there was no significant difference between the the amplitude of 200 μg group and that of control group (P > 0.05). However, the amplitude of the 400 μg group decreased continuously and there was still significant difference (P < 0.05). Light microscopy did not reveal any corneal abnormality in both control group and voriconazole groups. The retinas were normal except that of the 400 μg group, which hadathinner and degenerated inner nuclear layer and disordered photoreceptor layer. Under transmission electron microscope, there were no ultrastructure damages of corneas in both control group and voriconazole groups, either. The rabbit retinas of the 50 μg and 200 μg group have normal inner nuclear layer and photoreceptor layer, but degrees of changes in both layers were observed in the eyes of 200 μg and 400 μg group. Conclusions There is no obvious effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at he dose less than or equal 100 μg. There are no obvious effects on rabbit corneas at the dose of 200 μg and 400 μg, while there are damages to the retinas in both functions and histological structures.