1887

Abstract

In this study, we investigated the antifungal effects of itraconazole/voriconazole (ITR/VRC) alone and in combination with tetrandrine (TET) against 23 clinical isolates of using a chequerboard microdilution method. The dynamic antifungal effects of TET with ITR/VRC against were assessed using time–kill curves following systemic infection of mice with . After treatment, efflux pump activity was determined by the efflux of rhodamine 6G (R6G). When ITR was combined with TET, ITR MICs were reduced from 0.125–32 to 0.0625–2 μg ml, and TET MICs were reduced from 256–512 to 8–64 μg ml. When VRC was combined with TET, VRC MICs were reduced from 0.125–2 to 0.03125–0.5 μg ml, and TET MICs were reduced from 256–512 to 8–256 μg ml. Time–kill curves revealed that viability was reduced after treatment with ITR/VRC combined with TET versus ITR/VRC alone. ITR/VRC combined with TET significantly prolonged mouse survival and reduced kidney and brain tissue burdens versus ITR/VRC alone ( < 0.05). Moreover, TET inhibited R6G efflux of . Thus, and , TET acted synergistically with ITR/VRC against , and the synergistic mechanism was related to inhibition of the drug efflux pump.

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2015-09-01
2022-01-19
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