POSTANTIBIOTIC EFFECT AND POSTEXPOSURE PO LYENE ANTAGONISM OF AZOLE ANTIMYCOTICS IN CANDICA ALBICANS - DEPENDENCY ON LIPOPHILIA

With the lipophilic azoles itraconazole (ICZ), ketoconazole (KCZ), and miconazole (MCZ) two effects, occurring in parallel, on Candida albic ans were observed: Firstly, these azoles caused a growth inhibition wh ich persisted for at least 24 hours (post-antibiotic effect, found reg ularly with KCZ and MCZ, with ICZ only occasionally). Furthermore, the fungicidal activity of amphotericin B (AMB, 1 mg/l) after exposure to the azoles was reduced. In contrast to this, fluconazole (FCZ) produc ed neither of these effects. Additional experiments indicate that both actions of the three lipophilic azoles may be related to their noncov alent binding to lipophilic cytoplasmatic components of the yeast cell s. In the case of fluconazol such bonds seem to be much weaker. Presum ably, the amount of the relatively hydrophilic fluconazole, which will be bound to the cell, is too low as to produce longlasting post-expos ure effects like those caused by the lipophilic azoles.