Effect of amphotericin B, fluconazole and itraconazole on intracellular Candida albicans and germ tube development in macrophages.
Candida albicans may resist intracellular killing by macrophages through the formation of germ tubes. Antifungal drugs that inhibit intracellular germ tube formation could therefore facilitate host defence against C. albicans. We assessed the effects of amphotericin B and the new triazole drugs fluconazole and itraconazole on the multiplication and intracellular germ tube formation of C. albicans phagocytosed by murine peritoneal macrophages, and compared the findings with the effects of these drugs on C. albicans in the absence of macrophages. The fungicidal effect of amphotericin B against C. albicans in macrophages was less prominent than that found for extracellular candida. However, amphotericin B completely blocked germ tube formation of C. albicans both in macrophages and extracellularly. Fluconazole and itraconazole had little effect on the number of candida but significantly, although incompletely, inhibited germ tube formation both inside macrophages and extracellularly. The inhibition of intracellular germ tube formation by the triazoles may facilitate host defences against C. albicans and contribute to the efficacies of these drugs in vivo.
Van 't Wout
J W
JW
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Meynaar
I
I
Linde
I
I
Poell
R
R
Mattie
H
H
Van Furth
R
R
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D015725:Fluconazole / Q000494:pharmacology*; D017964:Itraconazole; D007654:Ketoconazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects
D000935:Antifungal Agents; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D007654:Ketoconazole