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The generation of a new antifungal againstCandida albicans biofilms has become a major priority, since biofilm formation by this opportunistic pathogenic fungus is usually associated with an increased resistance to azole antifungal drugs and treatment failures. Miltefosine is an alkyl phospholipid with promising antifungal activity. Here, we report that, when tested under planktonic conditions, miltefosine displays potentin vitro activity against multiple fluconazole-susceptible and -resistantC. albicans clinical isolates, including isolates overexpressing efflux pumps and/or with well-characterized Erg11 mutations. Moreover, miltefosine inhibitsC. albican s biofilm formation and displays activity against preformed biofilms. Serial passage experiments confirmed that miltefosine has a reduced potential to elicit resistance, and screening of a library ofC. albicans transcription factor mutants provided additional insight into the activity of miltefosine againstC. albicans growing under planktonic and biofilm conditions. Finally, we demonstrate thein vivo efficacy of topical treatment with miltefosine in the murine model of oropharyngeal candidiasis. Overall, our results confirm the potential of miltefosine as a promising antifungal drug candidate, in particular for the treatment of azole-resistant and biofilm-associated superficial candidiasis.

antimicrobial agents and chemotherapy

<i>In Vitro</i> Activity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions and <i>In Vivo</i> Efficacy in a Murine Model of Oral Candidiasis

In Vitro Activity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions and In Vivo Efficacy in a Murine Model of Oral Candidiasis