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.

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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES) under Grant 001.

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VSF contributed to the conception and design of the study, data acquisition, data analysis and interpretation, writing and critical review of the manuscript. TFR, MBS and AB assisted in the design, analysis, interpretation of data and critical review of the manuscript. LNF and BRP performed the collection of clinical samples and isolation of strains. RH participated in the conception and experimental design, analysis and interpretation of data and critical review of the manuscript. All authors read and approved the final article.

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Correspondence to Rosmari Hörner.

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Foletto, V.S., da Rosa, T.F., Serafin, M.B. et al. Repositioning of antidepressant drugs and synergistic effect with ciprofloxacin against multidrug-resistant bacteria. World J Microbiol Biotechnol 37, 53 (2021). https://doi.org/10.1007/s11274-021-03016-3

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Keywords

  • Antibacterial activity
  • Antidepressant
  • Fluoxetine
  • Paroxetine
  • Synergism