OBJECTIVE To explore the synergistic effect of clorgiline and voriconazole on inhibition of bacteria and formation of biofilms in vitro so as to provide experiment bases for clinical treatment of drug-resistant Candida albicans infection.
METHODS Minimum inhibitory concentrations (MICs) of voriconazole and clorgiline against two strains of C.albicans were explored by broth microdilution method. The synergistic effect of the two drugs on inhibition of bacteria were evaluated by chessboard method, and the fractional inhibitory concentration index (FICI) was calculated. The potential mechanisms of clorgiline for synergistically boost the effect of voriconazole were studied by rhodamine 6G (R6G) efflux pump test; the effects of the single and combined use of the two drugs on inhibition of the biofilms were explored by crystal violet staining method.
RESULTS The MICs of the single voriconazole against the 2 strains of C. albicans were 0.25 μg/ml and 8 μg/ml, respectively; the MICs were decreased to 0.0625 μg/ml and 0.5 μg/ml, respectively, after its combination with clorgiline. The FICIs of the combined use of the two drugs against the two strains were both less than 0.5, showing synergistic antibacterial effect. The result of R6G efflux pump experiment indicated that clorgiline inhibited the efflux of R6G within 2 hours. The biofilm formation experiment showed that the single use of voriconazole or clorgiline had limited effect on inhibition of biofilm formation, and the combined use of the two drugs could inhibit the biofilm formation.
CONCLUSIONS Clorgiline can enhance the antibacterial activity of voriconazole by inhibiting the efflux pump function of the C.albicans strains. The two drugs show remarkable synergistic effect on inhibition of the biofilm formation, which may provide novel strategies for combined use of drugs and theoretical bases for treatment of the drug-resistant C.albicans infection.
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