Combination therapy of micafungin with voriconazole and amphotericin B against Candida biofilms

Kaneko Y., Ohno H., Imamura Y., Kohno S., Miyazaki Y.

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Background: To date, combination treatment remains an empirical strategy in patients with difficult-to-treat infections including biofilm-associated infections, and basic evidence about the efficacy of combination therapy against biofilms is urgently demanded. Here we compared the effect of the combination treatment of micafungin (MCFG) with voriconazole (VRC) and amphotericin B (AMB) against planktonic cells and biofilms of Candida albicans. Methods: C albicans, SC5314, was used with MCFG, VRC and AMB. Susceptibility testing was performed by broth microdilution (two-fold dilution) in several combinations. To make biofilms, silicone elastomer (SE) disks (4mm diameter) were immersed in a Candida cell suspension and incubated for 90 min at 37°C, and the disks were then incubated in yeast nitrogen base (YNB) medium with 2% dextrose for 24 hours. After planktonic cells or biofilms were treated with several combinations, XTT reduction assay was performed for viability test and MICs and FIC indexes were calculated. Results: FIC indexes against planktonic cells of MCFG+VRC and MCFG+AMB were both 1. FTC indexes against biofilms of MCFG + AMPH and MCFG + VCZ were I and >2, respectively. Since combination of MCFG and VRC showed antagonism on biofilms in contrast to planktonic cells, we performed time-lag treatment to examine if the attenuation effect of VRC continues after removal of the drug. Biofilms were treated with VRC or MCFG alone, or without any drugs for the first 24 hours and then were treated with another drug alone or combination of VRC and MCFG for the next 24 hours. Simultaneous or serial combinations of VRC followed by MCFG were less effective than MCFG alone or MCFG followed by VRC. Conclusions: We should beware of the antagonisms within practicable combinations antifungal agents on biofilms. Studies of the mechanism of the antagonism revealed in the present work should provide clues for new antifungal strategies.

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17th International Society for Human and Animal Mycology
    • ISHAM 17th (2009)