Hydrocortisone, prednisolone and dexamethasone act on Aspergillus fumigatus in vitro susceptibility to itraconazole.

In a previous in vitro investigation from the same laboratory a therapeutic level of hydrocortisone enhanced the itraconazole susceptibility of a single strain of Aspergillus fumigatus. In the present work, the influence of therapeutic levels of hydrocortisone (1 microM), prednisolone (0.125 microM 0.25 microM and 0.5 microM) and dexamethasone (0.25 microM and 0.5 microM) on the itraconazole susceptibility of four A. fumigatus strains, was determined. A. fumigatus conidia were germinated either in the absence or in the presence of a glucocorticoid. The germinated conidia were then spread onto plates and grown either in the presence or in the absence of a glucocorticoid, together with increasing concentrations of itraconazole. The mean colony forming units (CFU) were measured. Two factor analyses of variance showed that hydrocortisone significantly (p <0.001) potentiated the action of itraconazole. The cytotoxic effect of prednisolone on the fungal strains added significantly to the effect of itraconazole (p <0.001). Dexamethasone was also cytotoxic to the fungus but, when used in conjunction with itraconazole, it effectively increased (p <0.01) the number of CFU. This study showed a direct effect of glucocorticoids, currently in use for patient therapy, on in vitro A. fumigatus susceptibility to itraconazole.

Does hydrocortisone modify the in vitro susceptibility of Aspergillus fumigatus to itraconazole and amphotericin B?

To analyse if hydrocortisone could modify the in vitro susceptibility of Aspergillus fumigatus to antifungal drugs, we developed a procedure to test the susceptibility of an A. fumigatus strain to amphotericin B and itraconazole, grown in the presence and in the absence of hydrocortisone. Conidia were germinated in the presence or the absence of hydrocortisone in Czapek medium without antifungal drug. A dilution of these cultures (5x10(3) conidia ml(-1)) was spread onto Czapek-agarose plates containing both antifungal drug and hydrocortisone. The cfu per plate were enumerated and compared. A therapeutic concentration of hydrocortisone induced a significant increase in the susceptibility to itraconazole. Conversely, the susceptibility to amphotericin B was not significantly modified when this antifungal drug was associated with hydrocortisone.