Repositioning of fluoxetine and paroxetine: study of potential antibacterial activity and its combination with ciprofloxacin

• Published in: Medicinal chemistry research 2020-03, Vol.29 (3), p.556-563
• Main Authors: Foletto, Vitória S., Serafin, Marissa B., Bottega, Angelita, da Rosa, Taciéli F., Machado, Catrine de S., Coelho, Silvana S., Hörner, Rosmari
• Format: Article
• Language: English
• Subjects: American Type Culture Collection; Antibacterial activity; Antibiotics; Antidepressants; Antimicrobial agents; Bacteria; Bacterial diseases; Bacterial infections; Bactericidal activity; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Ciprofloxacin; Clinical isolates; Drugs; E coli; Fluoxetine; Infectious diseases; Microorganisms; Minimum inhibitory concentration; Multidrug resistance; Original Research; Paroxetine; Pharmacology/Toxicology; Serotonin; Serotonin uptake inhibitors; Statistical analysis; Strains (organisms); Therapy
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-020-02507-6

Bacterial resistance has increased due to the indiscriminate use of antimicrobials over the years, limiting the available therapy in the treatment of infectious diseases. In this sense, the repositioning of approved drugs becomes a promising alternative. Therefore, the present study evaluated the antibacterial activity of antidepressants fluoxetine and paroxetine, belonging to the selective serotonin reuptake inhibitor (SSRI) class, and the effect of their association with the ciprofloxacin antibiotic. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), fractional inhibitory concentration index (FICI), and tolerance level were determined against each microorganism tested. The tests were performed against 11 bacterial standard reference strains from the American Type Culture Collection (ATCC) and five clinical isolates from patients admitted to a university hospital, being two multidrug resistant (MDR). The SSRIs, nonantibiotic drugs, presented antibacterial activity against all Gram negative and Gram positive strains tested, being the most expressive activity against Acinetobacter baumannii MDR and Escherichia coli ATCC 35218, both with MIC 32 μg mL −1 . These drugs showed five synergistic events when combined with ciprofloxacin against two ATCC standard strains and one MDR clinical isolate. Statistical analysis determined significance of antidepressants when associated with ciprofloxacin. Fluoxetine and paroxetine presented bactericidal activity against most of the microorganisms tested. Our results suggest the repositioning of these two antidepressants as broad spectrum antibiotic therapy for the treatment of bacterial infections. However, further studies on the mechanism of action of these drugs in relation to antibacterial activities are needed in order to increase the safety of their use.