Antibacterial Synergism of Fluoxetine and Paroxetine with Ceftriaxone, Plasmid DNA Cleavage and Repositioning

The indiscriminate use of antibiotics continues to promote a decrease in the sensitivity of bacteria to commercialized antibiotics. Current successful approaches, such as repositioning, enhance new uses for approved drugs. The antibacterial activity of fluoxetine (FX) and paroxetine (PX) combined with ceftriaxone (CTX) was evaluated against 5 standard strains and 72 multidrug-resistant clinical isolates collected in the years 2019 and 2021. FX showed minimum inhibitory concentrations (MIC) from 4 to 256 µg/ml and PX from 1 to 256 µg/ml, demonstrating that antidepressants showed better action than antibiotics (MIC from 512 µg/ml to > 4096 µg/ml). CTX had MIC reduced by 32 thousand times in combination with FX/PX. Antidepressants cleaved plasmid DNA by hydrolytic mechanism, demonstrating greater cleavage efficiency at pH 7.4 and temperature of 37 °C, that is, under physiological conditions. This is a demonstrative study of the promising action of FX/PX in combination with CTX in strains registered in 2019 and 2021, confirming it to be a promising alternative in antibacterial treatments.