Antifungal Susceptibility of<i>Candida</i>Biofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins

<jats:title>ABSTRACT</jats:title><jats:p>Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that<jats:italic>Candida</jats:italic>biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of<jats:italic>Candida albicans</jats:italic>and<jats:italic>Candida parapsilosis</jats:italic>biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles, amphotericin B lipid formulations, and echinocandins) have activities against<jats:italic>Candida</jats:italic>biofilms. We also explored effects of preincubation of<jats:italic>C. albicans</jats:italic>cells with subinhibitory concentrations (sub-MICs) of drugs to see if they could modify subsequent biofilm formation. Finally, we used confocal scanning laser microscopy (CSLM) to image planktonic- and biofilm-exposed blastospores to examine drug effects on cell structure.<jats:italic>Candida</jats:italic>biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays. Susceptibility testing of fluconazole, nystatin, chlorhexidine, terbenafine, amphotericin B (AMB), and the triazoles voriconazole (VRC) and ravuconazole revealed resistance in all<jats:italic>Candida</jats:italic>isolates examined when grown as biofilms, compared to planktonic forms. In contrast, lipid formulations of AMB (liposomal AMB and AMB lipid complex [ABLC]) and echinocandins (caspofungin [Casp] and micafungin) showed activity against<jats:italic>Candida</jats:italic>biofilms. Preincubation of<jats:italic>C. albicans</jats:italic>cells with sub-MIC levels of antifungals decreased the ability of cells to subsequently form biofilm (measured by DW;<jats:italic>P</jats:italic>< 0.0005). CSLM analysis of planktonic and biofilm-associated blastospores showed treatment with VRC, Casp, and ABLC resulted in morphological alterations, which differed with each agent. In conclusion, our data show that<jats:italic>Candida</jats:italic>biofilms show unique susceptibilities to echinocandins and AMB lipid formulations.</jats:p>