Effects of the combination of ketoconazole and calmodulin inhibitors against Candida albicans in vitro. Short communication.

The susceptibility of 66 strains of Candida albicans from patients was tested against ketoconazole (Ktz), chlorpromazine (Chl) levomepromazine (Lev), haloperidol (Hal) and the combination of Ktz with these calmodulin inhibitors, using Sabouraud's broth. The minimal inhibitory concentrations (MICs) for 66 strains of C. albicans were as follows: Chl 192 +/- 11.4 micrograms/ml, Lev 306 +/- 16.4 micrograms/ml, Hal 464 +/- 13.8 micrograms/ml compared with Ktz 34.46 +/- 3.9 micrograms/ml. The combination of Ktz and calmodulin inhibitors in various ratios (1:1,1:2,2:1) was found to exert synergistic effect and the mean values of the combinations were: Ktz+Chl 3.45 +/- 0.35, 3.78 + 0.36, 5.58 + 0.4 micrograms/ml; Ktz+Lev 10.8 +/- 2.19, 9.7 +/- 2.23, 10.5 + 2 micrograms/ml; Ktz+Hal 6.4 +/- 1.7, 6.8 +/- 1.6, 7.28 +/- 1.5 micrograms/ml. These results were significantly different (p < 0.001) from those of ketoconazole. These findings indicate that some calmodulin inhibitors increase the antifungal activity of Ktz against C. albicans in vitro.