Rational selection of antifungal drugs to propose a new formulation strategy to control Candida biofilm formation on venous catheters

Abstract

Introduction Infections associated with medical devices are often related to colonization by Candida spp. biofilm; in this way, numerous strategies have been developed and studied, mainly in order to prevent this type of fungal growth. Aim Considering the above, the main objective of the present study is to make a rational choice of the best antifungal therapy for the in vitro treatment of the biofilm on venous catheters, proposing an innovative formulation of a film-forming system to coat the surface in order to prevent the formation of biofilms. Methodology Anidulafungin, fluconazole, voriconazole, ketoconazole, amphotericin B, and the association of anidulafungin and amphotericin B were tested against biofilms of C. albicans, C. tropicalis, and C. parapsilosis strains in microtiter plates and in a polyurethane catheter. Besides, anidulafungin, amphotericin B, and the combination of both were incorporated in a filmforming system and were evaluated against biofilm. Results The superior activity of anidulafungin was demonstrated in relation to the other antifungal agents. Although amphotericin B showed good activity, high concentrations were required. The combination showed a synergistic action, in solution and in the formulation, showing excellent results, with activity above 90%. Conclusion Due to the superiority of anidulafungin and the synergistic activity of the combination, these alternatives were the most promising options for use in a formulation proposal as a new strategy to combat the Candida spp. biofilm. These formulations demonstrated high in vitro performance in the prevention of biofilms, indicating that they are candidates with great potential for in vivo tests.

8‐hydroxyquinoline and quinazoline derivatives as potential new alternatives to combat Candida spp. biofilm

“…While clioquinol showed 90% inhibition at lower concentrations, the other two compounds tested had less pronounced activity. The promising character of these compounds is more evident when compared to the results presented in a previous study by antifungal agents of the azole class, such as fluconazole and ketoconazole, which even at high concentrations (640 and 320 μg ml −1 respectively) were not able to reach IBF 90 (Reginatto et al 2020).…”

“…When we compare the results presented by the compounds tested in this work with widely known and used antifungal agents, such as fluconazole, we can more clearly observe the promising character presented here. Fluconazole, previously tested by our research group, had PMICs with ranges of 1-64 μg ml −1 for 50% inhibition (standardized percentage by CLSI for determination of PMIC for this antifungal agent) (CLSI 2008;Reginatto et al 2020), while the compounds in this study had PMIC 50 intervals of 2-32 and 0Á5-4 μg ml −1 (PH100 and PH157 respectively), in the same order, PMIC 100 with intervals of 16-128 and 2-16 μg ml −1 .…”

“…However, the results found are above 50%, which represents good results. Widely used antifungal agents, such as fluconazole, had a mean inhibition activity of <90% (Reginatto et al 2020).…”

“…A film-forming system type formulation, in the form of a hydrogel, previously tested with other commercial antifungal agents (Reginatto et al 2020), was evaluated for its action when incorporated with compound PH157 at a concentration of 16 μg ml −1 . When the capacity of IBF on the polyurethane catheter of this formulation was evaluated (42Á68-78Á09%), in general, the results were maintained concerning the compound solution (Table 3).…”

“…In a previous study, it was shown that this formulation did not interfere with the activity of the antifungal agents incorporated in it, preserving its activity. Furthermore, this formulation is simple to prepare, has low cost, and facilitates the application of the compound in the catheter (Reginatto et al 2020).…”