The effect of fluconazole in combination with rifampin in vitro on 1 Candida albicans biofilms
Wenna Shi, Hui Li, Yuguo Liu, Xiang Zhang and Shujuan Sun
AbstractProduction of Candida albicans biofilms is one resistance mechanism of fluconazole in C. albicans 26 and accordingly biofilm-related infections pose a great challenge to antifungal therapy. In this study, each 27 of the three antibacterial agents of azithromycin, fosfomycin and rifampin, which could destroy bacteria 28 biofilms, was respectively tested in combination with fluconazole to verify whether they had synergistic 29 effects on C. albicans biofilms. The nature of drug interaction was interpreted by calculating fractional 30 inhibitory concentration index (FICI) and percentages of growth difference (?E) from the results of 31 checkerboard assay. In order to evaluate the potential of the three antibiotics on fluconazole penetrating 32 the biofilms, a penetrating experiment was explored. In addition, fluorescein diacetate staining method 33 was adopted to observe metabolic activity of the sessile cell. It was revealed that rifampin could work 34 synergistically with fluconazole against the biofilms, while only negligible antifungal effects were 35 observed for the other drug combinations. A potent synergistic interaction in vitro between fluconazole 36 and rifampin against the biofilms by a fluconazole-resistant strain was demonstrated by a FICI value of 37 0.035 and synergistic high-interaction percentages of 1256% as interpreted by the ?E model. Results of 38 the penetrating experiment indicated that fluconazole combined with rifampin markedly enhanced 39 inhibitory zone of an indicative organism. Fluorescence micrographs showed that the addition of rifampin 40 rendered the cellular metabolism largely reduced. To sum up, rifampin could sensibilize fluconazole’ 41 antifungal effect on C. albicans biofilms and the synergistic mechanism needs further investigating.
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