Avaliação da atividade antibiofilme da Fluoxetina e da Sertralina em modelo ex vivo de ferida

Abstract

The presence of biofilm in the wound bed is one of the main factors responsible for chronicity and the consequent stagnation of the wound healing process, Staphylococcus aureus and Pseudomonas aeruginosa are the primary microorganisms involved in this infection process and biofilm formation. Moreover, biofilms enhance microbial resistance to antibiotics and antiseptics. In this context, the potential repurposing of non-antimicrobial drugs emerges as a viable alternative. Drugs such as fluoxetine and sertraline have demonstrated antimicrobial and antibiofilm activity. Based on this premise, the present study aimed to investigate the antibiofilm activity of fluoxetine and sertraline in an ex vivo porcine skin wound model. Sixteen strains were used, including eight S. aureus and eight P. aeruginosa. The MIC values for fluoxetine and sertraline, ciprofloxacin, and PHMB range from 19.5 to 39 µL/mL, 0.06 to 8 µL/mL, and 97 to ≥25,000 µL/mL, respectively. Against P. aeruginosa, the MIC values ranged from 78.1 to 312.5 µL/mL, 0.0312 to 32 µL/mL, and 12,500 µL/mL, respectively. A significant reduction in the MIC of PHMB was observed when combined with fluoxetine (MIC/2 and MIC/4, p = 0.0002) and sertraline (MIC/2, p = 0.0002; MIC/4, p = 0.0003) against S. aureus, and with fluoxetine (MIC/2 and MIC/4, p = 0.0014) and sertraline (MIC/4, p = 0.03) against P. aeruginosa. Regarding biomass analysis in mature biofilms against S. aureus, fluoxetine showed a significant reduction at 156.2 µL/mL (p = 0.0043), while sertraline exhibited a significant reduction at 39 µL/mL (p = 0.0011). Against P. aeruginosa, fluoxetine showed a significant reduction at 625 µL/mL (p = 0.0067), and sertraline at 1250 µL/mL (p = 0.0033). In the antibiofilm analysis in the ex vivo model against S. aureus, both fluoxetine (p = 0.01) and sertraline (p = 0.04) demonstrated significant reduction compared to PHMB. However, against P. aeruginosa, a significant reduction was observed only with sertraline (p = 0.003). Both fluoxetine and sertraline exhibited antimicrobial and antibiofilm activity in vitro and ex vivo. The results not only highlight the potential for drug repurpose in infection treatment but also underscore the need for further research to investigate the molecular mechanisms of action of each drug against these microorganisms.