Effects of itraconazole on phagocytosis and killing of Candida glabrata by polymorphonuclear leucocytes from guinea pigs.

Abstract

Itraconazole, a systemically active antifungal, was tested for its effects on microscopically assessed phagocytosis and killing of Candida glabrata 233 in vitro. Yeast cells were exposed to itraconazole in culture and guinea-pig peritoneal polymorphonuclear leucocytes were exposed to the drug injected intraperitoneally in vivo. At a concentration of 10(-7) M and with exposure times of 1 h, itraconazole pre-treatment of the leucocytes had no effect on the ability of PMNL to ingest or kill C. glabrata. However, pre-treatment of the growing C. glabrata cells under the same conditions significantly increased their vulnerability to both phagocytosis and intracellular killing. Longer exposures of the yeasts to itraconazole further increased their susceptibility to leucocyte phagocytosis, and it also rendered the cells vulnerable to killing merely by immersion in sodium deoxycholate solution. These findings indicate that short exposures of C. glabrata to low itraconazole concentrations damages the cells sublethally and renders them highly susceptible to leucocyte killing. Itraconazole had no direct effects on leucocyte function itself.