Biofilm Formation and Effect of Caspofungin on Biofilm Structure of Candida Species Bloodstream Isolates

Abstract

Candida biofilms are microbial communities, embedded in a polymeric matrix, growing attached to a surface, and are highly recalcitrant to antimicrobial therapy. These biofilms exhibit enhanced resistance against most antifungal agents except echinocandins and lipid formulations of amphotericin B. In this study, biofilm formation by different Candida species, particularly Candida albicans, C. tropicalis, and C. parapsilosis, was evaluated, and the effect of caspofungin (CAS) was assessed using a clinically relevant in vitro model system. CAS displayed in vitro activity against C. albicans and C. tropicalis cells within biofilms. Biofilm formation was evaluated after 48 h of antifungal drug exposure, and the effects of CAS on preformed Candida species biofilms were visualized using scanning electron microscopy (SEM). Several species-specific differences in the cellular morphologies associated with biofilms were observed. Our results confirmed the presence of paradoxical growth (PG) in C. albicans and C. tropicalis biofilms in the presence of high CAS concentrations. These findings were also confirmed by SEM analysis and were associated with the metabolic activity obtained by biofilm susceptibility testing. Importantly, these results suggest that the presence of atypical, enlarged, conical cells could be associated with PG and with tolerant cells in Candida species biofilm populations. The clinical implications of these findings are still unknown.

In vitro assessment of the antifungal and paradoxical activity of different echinocandins against Candida tropicalis biofilms

“…This phenomenon has subsequently been described with other echinocandins and other Candida species (Chamilos et al, 2007;Fleischhacker et al, 2008;Melo et al, 2007). This effect appears to be species-, strain-and echinocandin-specific (Chamilos et al, 2007;Ferreira et al, 2009;Melo et al, 2007;Miceli et al, 2009a, b) and associated with chitin accumulation and ultrastructural alterations (Bizerra et al, 2011); however, the clinical significance of the PE remains unclear.…”

“…Depending on the geographical region, Candida tropicalis ranks from the second to the fourth leading cause of invasive candidiasis (Bassetti et al, 2006;Nucci et al, 2010;Pfaller et al, 2008;Tan et al, 2010). Multiple studies of echinocandins against most C. albicans biofilms have shown them to be effective at concentrations of 2 mg ml 21 or less (Bachmann et al, 2002;Cocuaud et al, 2005;Ferreira et al, 2009;Jacobson et al, 2008Jacobson et al, , 2009Kuhn et al, 2002;Miceli et al, 2009a). However, a paradoxical effect (PE) of echinocandins against C. albicans biofilms treated with high concentrations of caspofungin (CFG) has been described (Stevens et al, 2004).…”

The evaluation of Candida albicans biofilms formation on silicone catheter, PVC and glass coated with titanium dioxide nanoparticles by XTT method and ATPase assay

“…As a result of greater use of implanted medical devices than before, microbes in biofilm display increased resistance towards biocides; antibiotic chemotherapy as well decreased susceptibility to the host defense mechanisms (9, 10). Recent evidences have revealed that in more than 65 % microbial infection, biofi lms have critical role in infections and diseases associated biofilm and are becoming increasingly more diffi cult to treat (11). Candida is an important human fungal fl ora causing nosocomial infection.…”

Bacteriophage K for reduction ofStaphylococcus aureusbiofilm on central venous catheter material

“…Biofilm-associated organisms can also elicit disease processes by detachment of individual cells or aggregates of cells resulting in bloodstream infections, by production of endotoxin, or by providing a niche for the development of antibioticresistant organisms. [1][2][3] Approximately 250000 cases of intravascular catheter-related bloodstream infections occur in the United States each year, resulting in a mortality of between 12-25% with an estimated cost of treatment per episode of approximately $25000. [3][4][5][6][7][8][9][10] The standard management of catheter-related infection involves decisions regarding removal of the catheter and the administration of appropriate antibiotics.…”