CD101, a Novel Echinocandin, Possesses Potent Antibiofilm Activity against Early and Mature Candida albicans Biofilms.

Jyotsna Chandra,Mahmoud A Ghannoum

doi:10.1128/aac.01750-17

Jyotsna Chandra, Mahmoud A Ghannoum

Open Access

https://doi.org/10.1128/aac.01750-17

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Abstract

ABSTRACTCurrently available echinocandins are generally effective against Candida biofilms, but the recent emergence of resistance has underscored the importance of developing new antifungal agents that are effective against biofilms. CD101 is a long-acting novel echinocandin with distinctive pharmacokinetic properties and improved stability and safety relative to other drugs in the same class. CD101 is currently being evaluated as a once-weekly intravenous (i.v.) infusion for the treatment of candidemia and invasive candidiasis. In this study, we determined (i) the effect of CD101 against early and mature phase biofilms formed by C. albicans in vitro and (ii) the temporal effect of CD101 on the formation of biofilms using time-lapse microscopy (TLM). Early- or mature-phase biofilms were formed on silicone elastomer discs and were exposed to the test compounds for 24 h and quantified by measuring their metabolic activity. Separate batches were observed under a confocal microscope or used to capture TLM images from 0 to 16 h. Measurements of their metabolic activity showed that CD101 (0.25 or 1 μg/ml) significantly prevented adhesion-phase cells from developing into mature biofilms (P = 0.0062 or 0.0064, respectively) and eradicated preformed mature biofilms (P = 0.04 or 0.01, respectively) compared to those of untreated controls. Confocal microscopy showed significant reductions in biofilm thicknesses for both early and mature phases (P < 0.05). TLM showed that CD101 stopped the growth of adhesion- and early-phase biofilms within minutes. CD101-treated hyphae failed to grow into mature biofilms. These results suggest that CD101 may be effective in the prevention and treatment of biofilm-associated nosocomial infections.

Highlights

Available echinocandins are generally effective against Candida biofilms, but the recent emergence of resistance has underscored the importance of developing new antifungal agents that are effective against biofilms
Confocal laser scanning microscopy (CLSM) images of untreated control biofilms showed a heterogeneous architecture of biofilms comprising cells/hyphae embedded within the extracellular matrix (Fig. 2A)
C. albicans cells exposed to both concentrations of CD101 showed only remnants of adhered fungal cells which failed to develop into mature biofilms (Fig. 2B and C)

Summary

Introduction

Available echinocandins are generally effective against Candida biofilms, but the recent emergence of resistance has underscored the importance of developing new antifungal agents that are effective against biofilms. We determined (i) the effect of CD101 against early and mature phase biofilms formed by C. albicans in vitro and (ii) the temporal effect of CD101 on the formation of biofilms using time-lapse microscopy (TLM). Separate batches were observed under a confocal microscope or used to capture TLM images from 0 to 16 h Measurements of their metabolic activity showed that CD101 (0.25 or 1 ␮g/ml) significantly prevented adhesionphase cells from developing into mature biofilms (P ϭ 0.0062 or 0.0064, respectively) and eradicated preformed mature biofilms (P ϭ 0.04 or 0.01, respectively) compared to those of untreated controls. We (i) determined the effect of CD101 against early- and mature-phase biofilms formed by C. albicans in vitro and (ii) evaluated the temporal effect of CD101 on the formation of biofilms using real-time time-lapse microscopy (TLM). CD101 possesses a long half-life [20, 21] and demonstrates a prolonged efficacy with a wide safety margin [19, 20]

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Conclusion