Anti-Candida activity of antidepressants sertraline and fluoxetine: effect upon pre-formed biofilms

As an opportunistic fungal pathogen Candida spp. has the ability to form biofilms. The most prescribed drugs for Candida infections, azoles, have shown to be less effective when biofilms are present. In addition, increasing treatment costs and the fact that most prescribed antifungal drugs have only fungistatic activity justify the search for new treatment strategies. One promising approach is third generation antidepressants, selective serotonin re-uptake inhibitors (SSRIs), because of their proven antifungal activity against several Candida spp. Thus, the aim of this work was to determine the ability of two commonly used SSRIs, fluoxetine and sertraline, to impair both biofilm metabolic viability and biofilm biomass. The in vitro effect of fluoxetine and sertraline was individually tested against biofilm metabolic viability and biofilm biomass using the MTT assay and the Crystal Violet assay, respectively. For both drugs, a dose-dependent reduction on both biofilm metabolism and biomass was present. At high concentrations, fluoxetine was able to reduce biofilm metabolism by 96% (C. krusei) and biofilm biomass by 82% (C. glabrata), when compared to the control. At similar conditions, sertraline achieved a reduction of 88% on biofilm biomass (C. glabrata) and 90% on biofilm metabolism (C. parapsilosis). Moreover, fluoxetine showed interesting anti-biofilm activity at previously reported planktonic MIC values and even at sub-MIC values. These results reinforce the potential interest of SSRIs as anti-biofilm agents to be study to counteract resistance phenomena on candidosis.