Repositioning of antidepressant drugs and synergistic effect with ciprofloxacin against multidrug-resistant bacteria.

Abstract

The repositioning of drugs has been shown to be an advantageous alternative for treating diseases caused by multidrug-resistant (MDR) microorganisms. The study aimed to investigate the in vitro antibacterial activity of the antidepressants fluoxetine and paroxetine alone and in combination with the antibacterial ciprofloxacin against standard strains and clinical isolates to explore the repositioning of these drugs in severe bacterial infections. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), tolerance level, fractional inhibitory concentration index (FICI) and interaction of antidepressants with the ciprofloxacin antibiotic were determined using the Checkerboard method against six American Type Culture Collection (ATCC) standard strains and seventy MDR clinical isolates. Both antidepressants showed better antibacterial activity than ciprofloxacin, in addition to being separately bactericidal against all tested Gram-negative and Gram-positive strains. When associated with ciprofloxacin, fluoxetine and paroxetine exhibited significant synergism compared to seventy ciprofloxacin-resistant clinical isolates, demonstrating that these antidepressants were able to increase the antibacterial activity of the antibiotic by eight times. The combination of antidepressants with ciprofloxacin showed relatively better activity against Acinetobacter baumannii, Enterococcus faecium and Klebsiella pneumoniae, strains in which the FICI value obtained was 0.008. The MDR isolates tested in this study ratify the antibacterial properties of the non-antibiotic fluoxetine and paroxetine. In addition, synergism when associated with ciprofloxacin is an alternative for treating serious infections in hospitalized patients. However, additional in vivo studies must be conducted to elucidate the mechanisms of action of these drugs.