Rational selection of antifungal drugs to propose a new formulation strategy to control Candida biofilm formation on ven
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CLINICAL MICROBIOLOGY - RESEARCH PAPER
Rational selection of antifungal drugs to propose a new formulation strategy to control Candida biofilm formation on venous catheters Paula Reginatto 1,2 & Vanessa Zafanelli Bergamo 1 & Simone Jacobus Berlitz 3 & Irene Clemes Kulkamp Guerreiro 3,4,5 & Saulo Fernandes de Andrade 1,4,5 & Alexandre Meneghello Fuentefria 1,4,6 Received: 13 December 2019 / Accepted: 6 February 2020 # Sociedade Brasileira de Microbiologia 2020
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. Keywords Catheter . Polyurethane . Association . Film-forming system . Biofilm
Responsible Editor: Rosana Puccia Electronic supplementary material The online version of this article (https://doi.org/10.1007/s42770-020-00242-z) contains supplementary material, which is available to authorized users. * Paula Reginatto [email protected] 1
2
Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Laboratório de Micologia Aplicada, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
3
Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
4
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
5
Departamento de Produção de Ma
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