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It is noteworthy that the tested antibiotics alone did not exhibit PLX4032 antifungal activity. The synergistic effect of the antibiotics could be related to the fact that amphotericin B binds to the sterols in the fungal cell membrane, thus increasing the antibacterial permeability; rifampicin interferes with RNA synthesis, while doxycycline interferes with protein synthesis. A recent study has also described synergistic effects between amphotericin B and clarithromycin, and between amphotericin B and rifampicin against Candida biofilms. Attending to such results, the association between the antibacterial agents tested could represent a very interesting therapeutical approach for the treatment of Candida biofilm-related infections (Del Pozo et al., 2011). Gao et al. (2013) explored the antifungal activity of fluconazole in combination with doxycycline against C. albicans. The results revealed a strong synergism against planktonic cells of fluconazole-resistant isolates. The same author��s also demonstrated a weaker antifungal effect of fluconazole combined with doxycycline against C. albicans biofilms compared with planktonic cells, being this effect time dependent. Miceli et al. (2009) also showed that doxycycline combined with fluconazole increased the killing activity of the antifungal upon biofilms by Candida sp. In this report, single doxycycline (2048 and 1024 mg/L) resulted in to 85% reduction of the metabolic activity of C. albicans biofilm; single fluconazole exhibited a lower activity (22.9 % reduction); interestingly, the combination of both compounds resulted in an additive effect. Such results suggest that high-dose doxycycline in combination with standard antifungal agents might play an important role in the treatment of Candida biomaterial-related, like is the case of medical indwelling device infections. A recent study showed that fluconazole acts synergistically with minocycline against fluconazole-resistant C. albicans, resulting in a significant decrease of the MIC value when both compounds are combined comparatively to single fluconazole (Shi et al., 2010). This combination could represent a valid option to overcome fluconazole resistance. The minimum inhibitory concentrations for 80% of inhibition (MIC80) of fluconazole and minocycline were 512 and 256 mg/L, respectively. The results revealed that a concentration of 4 mg/L of minocycline (which corresponds to a concentration easily achieved in human serum and other body fluids with conventional therapeutic dosages), in combination with fluconazole resulted in a fluconazole MIC decrease to 8 mg/L. Data from the literature clearly demonstrate that it is very difficult for fluconazole to penetrate C. albicans biofilms when used alone. However, with the association of minocycline the amount of fluconazole penetrating C.