Repurposing of paroxetine and fluoxetine for their antibacterial effects against clinical Pseudomonas aeruginosa isolates in Egypt.

Abstract

Background: Drug repositioning has emerged as a promising strategy for assessing its antimicrobial efficacy in treating infectious diseases.

Methods: Seventy-five samples were collected and investigated for the presence of Pseudomonas aeruginosa. Antibiotic resistance, hemolytic activity, twitching motility, and biofilm formation were assessed. lasI and lasR genes were detected using conventional PCR. Minimum inhibitory concentrations of paroxetine, fluoxetine, and levofloxacin were determined by broth micro-dilution. The fractional inhibitory concentration index was calculated to assess the interaction between fluoxetine/levofloxacin and paroxetine/levofloxacin combinations. Half the MIC values of the drugs were selected for inhibitory effect assessment for virulence factors. Antibacterial and healing effects of fluoxetine were investigated on 30 male albino rats using a digital camera, bacterial count, and histological examination.

Results: Our 25 P. aeruginosa isolates were highly drug-resistant. 80%, 92%, and 80% of isolates were positive for twitching motility, hemolysis, and biofilm formation, respectively. 92% of isolates were positive for lasI gene and 96% for lasR gene. MICs of fluoxetine and paroxetine ranged from 32 to 512 µg/mL and MICs of levofloxacin ranged from 1 to 256 µg/mL. A synergistic outcome was observed in both combinations. Biofilm formation, twitching motility, and hemolysis were inhibited by paroxetine and fluoxetine in the majority of isolates. Fluoxetine/levofloxacin and paroxetine/levofloxacin combinations inhibited twitching motility, hemolysis, and biofilm formation in all isolates. Enhanced wound healing was observed in rats treated with fluoxetine and levofloxacin, with the fluoxetine/levofloxacin combination group demonstrating the most significant wound-healing effect. Bacterial count decreased in rats treated with levofloxacin, fluoxetine, and the levofloxacin/fluoxetine combination. Histological examination revealed higher wound healing in the levofloxacin-treated group than the fluoxetine group, and the combination treatment group displayed the fastest rate of wound healing.

Conclusions: Paroxetine and fluoxetine showed considerable antibacterial inhibitory effects against multi-drug resistant P. aeruginosa isolates. Fluoxetine showed significant improvement in anti-inflammatory effects and wound healing. To the best of our knowledge, this is the first Egyptian study to investigate the repurposing of paroxetine and fluoxetine as antibacterial agents. Further studies are needed to investigate their applicability as antibacterial agents as single agents or in combination with other antibiotics.