Antimicrobial, Synergistic, and Antibiofilm Activity of Sildenafil Against Pseudomonas aeruginosa: Preliminary Studies

The present study tested sildenafil citrate as an example of pharmacological repositioning against the opportunistic pathogen Pseudomonas aeruginosa, known for its potent biofilm formation. We evaluated its antimicrobial, synergistic, and antibiofilm effects using broth microdilution, checkerboard assays, and atomic force microscopy techniques. Sildenafil citrate showed antimicrobial activity, effectively inhibiting bacterial growth at minimum inhibitory concentrations ranging from 3.12 to 6.25 mg/mL and minimum bactericidal concentrations between 3.12 and 25 mg/mL. When combined with reference antimicrobial agents-cefepime, imipenem, cilastatin, and polymyxin-sildenafil citrate had a synergistic effect. It also effectively inhibited and eradicated biofilms, reducing total biomass by 87.1% for inhibition and 83.8% for eradication. Atomic force microscopy confirmed the efficacy of sildenafil citrate in destroying and inhibiting biofilms, decreasing the overall amplitude of the biofilm. Consequently, sildenafil citrate appears to be a promising candidate for combination with commercial antimicrobial drugs to prevent and treat P. aeruginosa infections.