Objectives: Candidiasis can be associated with the formation of biofilms on bioprosthetic surfaces and the intrinsic resistance of Candida albicans biofilms to the most commonly used antifungal agents has been demonstrated. In this study, we report on the antifungal activity of caspofungin at two different concentrations, on C. albicans and Candida parapsilosis biofilms with different ages of maturation. Methods: Fifteen strains of C. albicans (10 strains susceptible to fluconazole in vitro and five strains resistant to this antifungal agent) and six strains of C. parapsilosis (all were susceptible to fluconazole in vitro) were studied. The antifungal activity of caspofungin was assessed by looking for a significant inhibition of the metabolic activity of yeasts within biofilms. Biofilms of Candida were produced in vitro, on silicone catheters. Results: Caspofungin used at MIC did not modify the metabolic activity of C. albicans, whatever the maturation age of the biofilms. The same concentration of caspofungin significantly reduced the metabolism (P ≤ 0.001) of 25% (biofilms of 48 h) to 50% (biofilms of 2 h) of the C. parapsilosis yeasts. The use of a therapeutic concentration of caspofungin (2 mg/L) significantly decreased (P ≤ 0.001) the metabolism of all the strains of C. albicans and C. parapsilosis tested, independently of the biofilm maturation age. This potent antifungal activity of caspofungin on C. albicans biofilms was observed independently of the yeast susceptibility to fluconazole. Conclusions: This study demonstrated that caspofungin used at MIC was not sufficient to reduce C. albicans biofilms, but it suggested an activity on C. parapsilosis biofilms depending on their maturation age. This study also indicated that caspofungin used at 2 mg/L could be a good candidate in the prevention of candidiasis associated with silicone medical devices. Our results also suggested that fluconazole resistance of yeasts did not affect caspofungin activity.

Candida albicans is a commensal coloniser of the human gastrointestinal tract and an opportunistic pathogen, especially thanks to its capacity to form biofilms. This lifestyle is frequently involved in infections and increases the yeast resistance to antimicrobials and immune defenses. In this context, 38 lichen acetone extracts have been prepared and evaluated for their activity against C. albicans planktonic and sessile cells. Minimum inhibitory concentrations of extracts (MICs) were determined using the broth microdilution method. Anti-biofilm activity was evaluated using tetrazolium salt (XTT) assay as the ability to inhibit the maturation phase (anti-maturation) or to eradicate a preformed 24 h old biofilm (anti-biofilm). While none of the extracts were active against planktonic cells, biofilm maturation was limited by 11 of the tested extracts. Seven extracts displayed both anti-maturation and anti-biofilm activities (half maximal inhibitory concentrations IC_{50_mat} and IC_{50_biof} ≤ 100 µg/mL); Evernia prunastri and Ramalina fastigiata were the most promising lichens (IC_{50_mat} < 4 µg/mL and IC_{50_biof} < 10 µg/mL). Chemical profiles of the active extracts performed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) have been analyzed. Depsides, which were present in large amounts in the most active extracts, could be involved in anti-biofilm activities. This work confirmed that lichens represent a reservoir of compounds with anti-biofilm potential.

Candida infections associated with catheters remain difficult to manage. Antifungal lock strategies could be a therapeutic option when the device is difficult to remove or in combination with systemic treatment to increase efficacy. This study deals with the antibiofilm potential of liposomal amphotericin B (L-AMB) used as a lock solution to inhibit Candida albicans, Candida glabrata and Candida parapsilosis biofilms in vitro. Biofilms aged 12 h and 5 days were formed on silicone catheters. L-AMB (200 or 1000 mg/L) was added to biofilms and catheters were incubated for 4, 12 or 24 h at 37°C. L-AMB was then removed by washing. The metabolic activity of yeasts was assessed by the XTT method up to 48 h after the end of the locks to evaluate the persistence of the antibiofilm activity. Controls without antifungal were used as references to calculate the inhibition percentages induced by L-AMB lock solutions. L-AMB (200 and 1000 mg/L) inhibited, for up to 48 h, C. albicans and C. glabrata biofilms by >70%, regardless of the lock duration. The activity of L-AMB (200 mg/L) against C. parapsilosis mature biofilms was lower and less sustained, especially for 4 h locks. L-AMB (1000 mg/L) lock solutions strongly inhibited Candida spp. in young and mature biofilms for up to 48 h after the end of the lock. However, overall eradication of the biofilm was not obtained using 1000 mg/L L-AMB as a single lock. These results suggest the usefulness of systemic treatment combined with an L-AMB lock to control Candida spp. biofilms associated with catheters.

Objectives: Some manifestations of candidiasis are associated with the formation of biofilms on inert or biological surfaces and the intrinsic resistance of Candida albicans biofilms to the most commonly used antifungal agents has been demonstrated. In this study, we report on the influence of the growth of C. albicans in medium containing a sub-inhibitory concentration (MIC/2) of caspofungin, on subsequent fungal adherence to plastic coated with extracellular matrix (ECM) proteins. Methods: Eleven strains of C. albicans were studied: six strains were susceptible to fluconazole in vitro and five strains were resistant to this antifungal agent. Results: Caspofungin induced a decrease in the adherence of all the tested strains that were susceptible to fluconazole but induced a decrease in the adherence of only 60% of the fluconazole-resistant strains. Conclusions: This study demonstrated the anti-adherent activity of caspofungin but indicated a reduced effect in the case of in vitro fluconazole resistance. These results indicated a possible relationship between the efficiency of caspofungin to inhibit the first step of the development of C. albicans biofilm and the resistance of C. albicans to fluconazole in vitro.

Candidemia related to the presence of a biofilm are often reported in patients with vascular catheters. Once they are mature, biofilms are persistent infectious reservoirs, and the yeasts dispersed from biofilms can cause infections. Sessile yeasts typically display increased levels of resistance to most antimicrobial agents and systemic treatments usually fail to eradicate previously formed fungal biofilms. In a curative strategy, antifungal lock therapy may help to sterilize catheters, with very high concentrations of antifungal agents, which are not compatible with systemic use. This strategy has been studied by several authors in in vitro and in vivo studies, and more rarely, in clinical settings for adult and paediatric patients. Our study aims to assess the efficacy of the antifungal solutions used for lock therapy and demonstrated by the different teams.

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