Identification and evaluation of besifloxacin as repurposed antifungal drug in combination with fluconazole against Candida albicans

Abstract

Emergence of life-threatening fungal infections like systemic candidiasis concurrently with bacterial infections and limitations of current antifungal therapies warrants the discovery of novel inhibitors. We identified besifloxacin (BS), an FDA-approved antibacterial, as a potent antifungal inhibitor. A combination of besifloxacin with fluconazole showed a positive synergy ({delta} = 29.58) resulting in 80% inhibition of microbial growth. BS was able to reduce the MIC of FLC from 2mg/L to 0.5 mg/L when used in combination. Additionally in murine systemic Candida infection, BS reduced fungal load by 83% in mice kidneys at a dose of 100 mg/kg/day. The findings demonstrated the antifungal potential of BS, proposing its use in combination therapy with fluconazole to combat resistance through alternative mechanisms. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=165 HEIGHT=200 SRC="FIGDIR/small/642842v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1ed17org.highwire.dtl.DTLVardef@74b345org.highwire.dtl.DTLVardef@1a5aea3org.highwire.dtl.DTLVardef@6c816a_HPS_FORMAT_FIGEXP M_FIG C_FIG