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In vitro activity of rilopirox against fluconazole‐susceptible and fluconazole‐resistant Candida isolates from patients with HIV infection

The in vitro antifungal activity of the new hydroxypyridone antimycotic rilopirox has been evaluated against 38 fluconazole‐susceptible and ‐resistant clinical isolates of Candida albicans together with other Candida species isolated from patients with human immunodeficiency virus (HIV) infection and oropharyngeal candidosis. Minimum inhibitory concentrations (MICs) of both rilopirox and fluconazole were measured by a microdilution method using high‐resolution medium supplemented with asparagine and glucose at pH 7.0. In comparison, an agar dilution technique was carried out for susceptibility testing of the antifungal agents. Rilopirox was found to be able to inhibit growth of all clinical yeast isolates. The rilopirox MICs at which 50% and 90% of strains were inhibited (MIC50 and MIC90 respectively), as determined by the microdilution method, were 4 and 8 μg ml−1 respectively. The highest MIC values for rilopirox using microdilution and the agar dilution method were 32 or 25 μg ml−1 respectively. On the other hand, for fluconazole, the MIC50 and MIC90 achieved were 0.5 and 128 μg ml−1, respectively, which means that the MIC90 value of fluconazole was 16‐fold higher than that of rilopirox. Using the agar dilution technique, the MIC values of rilopirox were in the range 0.006–25 μg ml−1 with a median of 3.12 μg ml−1. For fluconazole, the MIC90 value was four‐fold higher than that for rilopirox, indicating a considerable proportion of yeast strains with high MICs of 100 μg ml−1, suggesting in vitro resistance to this azole antifungal. All strains with diminished fluconazole susceptibility were susceptible to rilopirox. Even Candida krusei and Candida glabrata exhibited good in vitro susceptibility to rilopirox. Therefore, this new antifungal agent may be used as an alternative not only in the treatment of vaginal candidosis, but also in oropharyngeal Candida infections, e.g. in AIDS patients.