Avaliação in vitro da atividade antifúngica da Dobutamina contra cepas de Candida spp. resistentes ao fluconazol e determinação de sua possível atividade espécie-específica contra cepas de Candida glabrata

Abstract

Infections with non-albican Candida species have been taking up more and more space on the world stage, due both to advances in the medical field and the increase in populations considered more susceptible. C. glabrata is an opportunistic pathogen belonging to the normal human microbiota and is the main or the second most common cause of candidemia, intrinsically presenting greater resistance to fluconazole. Thus, it is necessary to search for new therapeutic strategies. The redirection of drugs and synergism between the components used in therapy are efficient strategies, which decrease the toxicity of drugs and also represent a saving of resources. The objective of the study was to evaluate the antifungal effect of dobutamine on clinical strains of Candida spp., especially against C. glabrata as well as its synergism with azois and its action on biofilm formation. The M27-A3 protocol was used for the determination of minimum inhibitory concentrations (MIC) and flow cytometry for elucidation of the possible mechanism of action. The tested isolates presented MICs, ranging from 2 - 32 μg/mL for dobutamine, with fungistatic effect. 82% of the strains showed synergism with fluconazole and 90% with itraconazole. The effect on biofilm formation was indifferent. Cytometry tests showed that dobutamine induces mitochondrial depolarization with a consequent increase in the formation of reactive intracellular oxygen species and loss of cellular homeostasis, which cause DNA damage leading to death.