Synergistic Effects of Fluconazole Combined with Doxycycline Against Dual-Species Cultures of Candida albicans and Staphylococcus epidermidis and the Mechanisms of Action

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 Delta E 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.

Automated summary

Combination therapy of fluconazole and doxycycline demonstrated a synergistic antimicrobial effect against dual-species cultures of Candida albicans and Staphylococcus epidermidis. The inhibition of biofilms and calcium dysregulation may contribute to the synergism. This finding provides potential insights into the treatment of bacterial and fungal coinfections.