ABSTRACT
Bacterial and fungal coinfections have posed great clinical challenges in recent years, and combination therapy may be a useful way to treat these mixed infections. The objective of this study was to find an effective drug combination to treat dual-species cultures of fungi and bacteria. In this study, we focused on poorly investigated mixed cultures of Candida albicans and Staphylococcus epidermidis. In this research, we investigated the effects of fluconazole (FLC) and doxycycline (DOX) against dual-species cultures of C. albicans and S. epidermidis. Both the fractional inhibitory concentration index model and ΔE model revealed a synergistic antimicrobial effect between FLC and DOX against the four groups of dual-species cultures. Mechanistic studies revealed that the synergism of FLC and DOX against dual-species cultures may be associated with the inhibition of biofilms and calcium dysregulation. Fluconazole+doxycycline appears to be a potential drug combination for the treatment of bacterial and fungal coinfections. These findings are of great significance for overcoming clinical bacterial and fungal coinfections and might provide novel insights into drug discovery for combination therapy.