Antifungal Susceptibility ofCandidaBiofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins

Abstract

Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis 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 Candida biofilms. We also explored effects of preincubation of C. albicans 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. Candida biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays.

Candida parapsilosis complex water isolates from a haemodialysis unit: biofilm production and in vitro evaluation of the use of clinical antifungals

“…In agreement with others researches, mature biofilms of C. albicans consisted of a dense network of yeast and hyphal elements (Chandra et al 2001, Ramage et al 2001, Seneviratne et al 2009). Mature biofilms of C. parapsilosis are structurally similar to those described by Kuhn et al (2002). Here, a basal blastospore layer or irregular groupings of blastospores were observed for C. parapsilosis, while C. orthopsilosis presented short filamentous forms, besides blastopores.…”

“…Confocal scanning laser microscopy (CSLM) -Biofilms were stained and CSLM was performed as described previously by Kuhn et al (2002). Biofilms were formed as described above for SEM.…”

A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing

“…This resistance is likely multifactorial and, among other mechanisms, may be due to i) high cellular density within the biofilm; ii) the protective effect of the biofilm exopolymeric material; iii) differential expression of genes linked to resistance, including those encoding efflux pumps; and iv) presence of a subpopulation of "persister" cells. However, newer antifungal agents, such as the echinocandins and liposomal formulations of amphotericin B, display increased efficacy against fungal biofilms 7,8 . Of note, the commonly used Clinical and Laboratory Standards Institute (CLSI) broth microdilution techniques for antifungal susceptibility testing are based on the use of planktonic populations and will not enable prediction of the drugs' efficacy against fungal biofilms 9 .…”

In Vitro Interaction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods

“…However, high concentrations of AMB (at least 8 g/ml) are needed to inhibit hyphal clumps (6,18) or mature mycelia in vitro (13), although AMB was seen to be significantly more effective against each phase of A. fumigatus biofilm development and to display more rapid effects than other antifungals, such as voriconazole or caspofungin (13). In contrast to AMB deoxycholate, unique efficacy against Candida (C. albicans and C. parapsilosis) biofilms grown on a bioprosthetic model was displayed by lipid-formulated AMB (19), probably due to the higher doses of drug present in these formulations. In another study, LAMB at 0.5 g/ml was able to eradicate a C. albicans biofilm in a continuous-flow catheter model, whereas fluconazole and caspofungin were less effective (20).…”