THE EFFECT OF THE NEW TRIAZOLE, VORICONAZOLE (UK-109,496), ON THE INTERACTIONS OF CANDIDA-ALBICANS AND CANDIDA-KRUSEI WITH ENDOTHELIAL-CELLS

In this study, we investigated how voriconazole affects specific endot helial ell interactions utilizing both fluconazole-susceptible(S) and resistant(R) Candida albicans strains (C, albicans(S) and C, albicans( R), respectively) as well as Candida krusei, Our data show that exposi ng C, albicans(S) to voriconazole significantly reduced its adherence to endothelial cells (p < 0.001), The adherence of C, albicans(R) to e ndothelial cells was not affected by treatment with either antifungal agent, Exposure of C, albicans to both agents inhibited germ tube form ation; however, voriconazole showed higher ability in inhibiting germi nation as compared with fluconazole, The effect of antifungals on germ ination was also tested during co-incubation of yeast cells with endot helial cells, Pretreated C, albicans(S) cells germinated on endothelia l cells in the presence of voriconazole or fluconazole, However, the d egree of germination was reduced by 81% and 16%, respectively, Similar results were observed with C, albicans(R), Our data demonstrate that voriconazole treatment reduced the median germ tube length of C, albic ans(S) and C, albicans(R) by approximately 60%, whereas fluconazole re duced the germ tube length of these strains by 27% and 63%, respective ly (P < 0.0001 for each comparison), We compared the efficacy of voric onazole and fluconazole in protecting endothelial cells against damage caused by C. albicans(S), C. albicans(R), and C, krusei, Voriconazole and fluconazole reduced C, albicans-mediated endothelial cell injury by about 90% and 40%, respectively (P < 0.01 for each comparison), Add itionally, voriconazole treatment significantly reduced C. krusei-medi ated injury to endothelial cells by 69% (P < 0.01), whereas fluconazol e did not exhibit significant protection (P < 0.6). These results demo nstrate that voriconazole, in addition to its direct inhibitory activi ty against fungi, may act against Candida spp. by interfering with cri tical host/parasite interactions, such as adherence and endothelial ce ll damage, as well as germination. Therefore, this triazole represents a new and promising agent for the treatment of disseminated candidal infections caused by both fluconazole-susceptible and -resistant speci es.