Degenerative changes in fungi after itraconazole treatment.

Changes in morphogenetic behavior and structural degeneration after exposure to itraconazole are illustrated in Candida albicans, Cryptococcus neoformans, Pityrosporum ovale, Paracoccidioides brasiliensis, Trichophyton rubrum, and Aspergillus fumigatus. With the exception of P. ovale, primary alterations are seen at the cell periphery and the cytoplasmic vacuoles in which lipid-like vesicles assemble. These changes are usually accompanied by a marked increase in cell volume, impaired cell division, or abortive hyphal outgrowth. The concentration of itraconazole necessary to induce irreversible structural degeneration (necrosis) depends greatly on the species used, the time of incubation, and the morphogenetic form in which the fungus is grown and varies from 10(-10) M (P. brasiliensis) to greater than 10(-6) M (C. albicans). Itraconazole achieves these effects either at a concentration comparable to that required for ketoconazole (C. albicans and C. neoformans); at concentrations 10- to 100-fold lower (P. ovale, T. rubrum, P. brasiliensis), or at concentrations 100-fold lower (A. fumigatus).