In-vitro effect of itraconazole, ketoconazole and amphotericin B on the phagocytic and candidacidal function of human neutrophils

Abstract

Neither itraconazole nor ketoconazole had significant effects on the phagocytosis or killing of Candida albicans blastospores by human neutrophil polymorphonuclear (PMN) leucocytes, whether following simultaneous addition of drug with the blastospores, prior treatment of the PMN cells with drug, or prior treatment of the blastospores with drug. Following simultaneous addition, amphotericin B caused significant impairment of phagocytosis in tests with PMN cells from one of two donors, but had no effect on subsequent killing of ingested blastospores. Prior treatment of PMN cells or blastospores with amphotericin B had no effect on phagocytosis or killing. In tests in which blastospores of an azole-sensitive and an azole-resistant strain of C. albicans were added to PMN cells, fewer than 25% of ingested blastospores of either strain had initiated germ tube formation after 6 h. Addition of ketoconazole had no effect on the proportion of ingested blastospores of either strain which germinated. Ketoconazole had no effect on germ tube elongation of ingested blastospores of the azole-resistant strain, but caused marked inhibition of germ tube elongation of ingested blastospores of the azole-sensitive strain. After 24 h, the azole-resistant strain had produced abundant mycelium and few phagocytic cells remained intact. With the azole-sensitive strain, PMN cells were still evident at 24 h, with ingested germ-tube-forming blastospores, most of which were dead.