Background The incidence of invasive aspergillosis （IA） has increased in frequency in immunocompromised patients with a variety of diseases. The poor prognosis might be due to limited treatment option. This study aimed to evaluate antifungal activity of ibuprofen against clinical isolates of aspergillus species, as well as its interaction with azoles or with amphotericin B or with micafungin. Methods Antifungal activity of ibuprofen against 10 strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus were tested with both disk diffusion assay and standard broth microdilution method. To determine whether ibuprofen combined with itraconazole, voriconazole, amphotericin B, or micafungin had interactive effects on aspergillus spp., we used both disk diffusion assay and Chequerboard method. Results As for disk diffusion method, ibuprofen produced a zone of growth inhibition with diameters of （20.1±3.9） mm at 48 hours of incubation. As for broth microdilution method, the minimal inhibitory concentration （MIC） ranges of ibuprofen against aspergillus spp. were 1000-2000 μg/ml, and the minimal fungicidal concentration （MFC） ranges of that was 2000-8000 μg/ml. For 2 of 5 isolates, when ibuprofen combined with itraconazole or voriconazole, the zones of growth inhibition were larger than those of the individual drug. The results of Chequerboard method showed that fractional inhibitory concentration index （FICI） ranges were 1.125-2.500. Conclusions Ibuprofen is active against aspergillus spp.. And ibuprofen does not affect the in vitro activity of itraconazole, voriconazole, amphotericin B or micafungin against aspergillus spp.
LI Li-juan CHEN Wei XU Hui WAN Zhe LI Ruo-yu LIU Wei
Background Glucocorticoid is speculated to be able to have Aspergillus fumigatus （A. tum/gatus） I^e~ng more susceptible to reactive oxygen species （ROS） by inhibiting Afyapl, the transcription factor activating protein-1 （AP-1） homologue in A. fumigatus, which may provide a clue to expand the clinical use of glucocorticoid in patients with fungal infections. In this study, we used dexamethasone to determine the direct effect on oxidative killing susceptibility of A. fumigatus in vitro, as well as the expression level of Afyapl gene and its target genes （catalase and superoxide dismutase （SOD） genes）. Methods A. fumigatus spores were treated with different concentrations （0, 0.02, 0.2 mg/ml） of glucocorticoids and assigned to four groups （A： 0.5 hour, B： 2 hours, C： 7 hours, D： 16 hours） according to the time of treatment. The H202 oxidative killing assay was done, using the standard method-spot test, in each group of A. fumigatus. We measured the oxidative killing susceptibility as well as the expression level of the gene Afyapl, CATA, SOD1 and SOD2 in A. fumigatus at each group. The antifungal susceptibility to itraconazole and amphotericin B in each group of A. fumigatus was also measured with M38-A2 method. Results The oxidative killing susceptibility of A. fumigatus was increased, consistent with the reduction of Afyapl, CATA, SOD1 and SOD2 gene expression level after being treated with dexamethasone for 0.5 hours. However, these observations were disappeared along with being treated for longer time. The antifungal susceptibility to itraconazole and amphotericin B in the A. fumigatus strains treated with dexamethasone indicated no change, compared with those without dexamethasone treatment. Conclusion Dexamethasone can have A. fumigatus being more susceptible to ROS when treated for shorter period （0.5 to 2 hours） via the reduction of Afyapl gene expression as well as the down-stream enzyme-coding gene expression.
