In vitro evaluation of the antibacterial activity of amitriptyline and its synergistic effect with ciprofloxacin, sulfamethoxazole-trimethoprim, and colistin as an alternative in drug repositioning

摘要

In the present study we evaluated the biological activity of amitriptyline, a tricyclic antidepressant, and its antibacterial activity was determined in vitro, individually and in combination with ciprofloxacin, sulfamethoxazole-trimethoprim, and colistin. Being tested against multi drug resistant clinical isolates and American Type Culture Collection (ATCC) standard strains, through the fractional inhibitory concentration index (FICI) and tolerance index. Their ability to cleave plasmid DNA was also analyzed. Amitriptyline showed activity against Gram-positive and Gram-negative bacteria. In combination with colistin, two strains of Klebsiella pneumoniae producing carbepenemase with a minimum inhibitory concentration of 4 mu g/mL were prominent. FICI demonstrated synergistic effect in 15 combinations with antibiotics. Amitriptyline was able to cleave the DNA at concentrations of 3.75 and 1.875 mM at pH 7.4 at 50 degrees C. The results obtained in this study allow us to suggest amitriptyline as a potential antibiotic in drug repositioning.