Reposicionamento dos antidepressivos fluoxetina e paroxetina e efeitos sinérgicos com ciprofloxacino frente bactérias multidroga resistentes

Abstract

The growing need for effective antimicrobial agents for the treatment of multidrug-resistant bacteria (MDR), mainly caused by nosocomial infections, leads to the use of alternative alternatives. The repositioning or redirection of existing drugs and synergism with antibacterial drugs is a promising approach in the development of new antimicrobials. In this sense, the present study aimed, in the first article, to present new indications for use for antidepressant drugs selective serotonin reception (SSRI) fluoxetine and paroxetine. In this letter to the editor, 39 studies were analyzed, which describe different actions presented by these drugs. Fluoxetine showed 19 different activities in addition to its well-known antidepressant action, and paroxetine 10 new indications. The bacterial strains against which the two drugs were evaluated were also described, and the type of study, in vitro (standard strains or clinical isolates) or in vivo. In the second manuscript, the in vitro antibacterial activity of fluoxetine and paroxetine was evaluated alone and in combination with the antibacterial ciprofloxacin against 6 American Type Culture Collection (ATCC) standard strains and 70 MDR clinical isolates from a university hospital. The two antidepressants showed better antibacterial activity when compared to ciprofloxacin, in addition to being, separately, bactericidal against all as tested strains. In addition, the two drugs studied showed promising activity against Gram-negative (GN) and Gram-positive (GP), inferring the broader spectrum. When associated with ciprofloxacin, fluoxetine and paroxetine, they are diagnosed in the face of all MDR clinical isolates tested, highlighting that they were resistant to ciprofloxacin. Fluoxetine and paroxetine are promising alternative alternatives in the treatment of infectious diseases caused by MDR microorganisms, in addition to presenting different indications, as demonstrated in the literature. Both antidepressants take alternative approaches to redirect drugs, however, further studies are needed to elucidate the mechanisms of action involved.