Synergistic effect of lactoferrin combined with fluconazole to overcome antifungal resistance in Candida species.

BACKGROUND

The incidence of drug-resistant candidiasis has increased in recent decades, leading to significant treatment challenges and high morbidity and mortality rates. The development of new therapeutic options is crucial, but it is a complex and time-consuming process; an interesting strategy to face this problem is to combine existing antifungal drugs with synergistic agents to enhance treatment efficacy, reduce dosage and prevent resistance development.

METHODS

We analyzed the activity of lactoferrin against 80 isolates of 14 Candida species, including Candida auris according to both EUCAST and CLSI guidelines. Moreover, interaction between fluconazole and lactoferrin was assessed by checkerboard method against a selection of 38 isolates of eight Candida species, and by time-kill curves against six isolates of two Candida species, including fluconazole susceptible and resistant isolates.

RESULTS

Synergistic and additive effects were demonstrated, with effective inhibition of Candida growth. Furthermore, combination therapy significantly reduced fluconazole minimum inhibitory concentrations (MICs) and showed synergistic effect against fluconazole-resistant isolates.

CONCLUSIONS

Lactoferrin has significant potential value in the treatment of candidiasis and further exploration of its potential clinical applications is of great importance. The ability of lactoferrin to enhance the efficacy of existing antifungal drugs while potentially reducing the development of antifungal resistance makes it an intriguing candidate for future research and development efforts.