Effects of subinhibitory concentrations of ketoconazole on in vitro adherence of Candida albicans to vaginal epithelial cells.

The in vitro adherence of multiple 14C-glucose labeled isolates of Candida albicans to exfoliated vaginal epithelial cells in the presence of subinhibitory concentrations of ketoconazole was studied with a new method utilizing differential centrifugation in a gelatin-PBS solution as well as by the standard method of direct microscopy measurement. Pre-incubation of stationary-phase candida in ketoconazole at concentrations of 0.002 to 0.1 microgram/ml for 4 h at 37 degrees C had no effect on adherence. The addition of ketoconazole to logarithmic phase Candida albicans failed to reduce the total number of cell-associated adherent yeast but exposure to subinhibitory concentrations of ketoconazole was associated with a dystrophic morphology of the blastospores, extensive clumping and reduced germination resulting in fewer individual candida blastospores directly attached to the cell membranes. Germination inhibition and a marked reduction in adherent candida was observed when 0.01 microgram/ml ketoconazole was added to Candida albicans incubated in germination promoting medium. The diminished adherence of Candida albicans to vaginal epithelial cells after exposure to subinhibitory concentrations of ketoconazole may have clinical relevance in preventing recurrent candida vaginitis.