In-Vitro Synergistic Activity of Nortriptyline in Combination with Vancomycin Against a Clinical Vancomycin-Intermediate Staphylococcus aureus (VISA): A Proof-of-Concept Study

Background: Staphylococcus aureus is an important pathogen responsible for a wide range of community-and hospital- acquired infections. The increasing prevalence of strains with reduced vancomycin susceptibility has limited therapeutic options. It underscores the need to identify novel antimicrobial combinations.Objectives: This proof-of-concept study aimed to evaluate the in vitro antibacterial activity of Nortriptyline and to investigate its interaction with vancomycin against a clinical vancomycin- intermediate Staphylococcus aureus (VISA) isolate.Methods: In this in vitro experimental study, a single clinical VISA isolate was evaluated. The minimum inhibitory concentrations (MICs) of Nortriptyline and vancomycin were determined by broth microdilution. Drug interactions were assessed using the checkerboard assay, and interactions were interpreted based on the fractional inhibitory concentration index (FICI).Results: The MICs of vancomycin and Nortriptyline alone were ۷.۸۱ µg/ml and ۱۰۰۰ µg/ml, respectively. When combined, the MICs of both agents decreased fourfold to ۱.۹۵ µg/ml and ۲۵۰µg/ml respectively. The calculated FICI was ۰.۵, indicating synergistic activity according to the predefined interpretation criteria.Conclusion: Nortriptyline exhibited in vitro synergistic activity in combination with vancomycin against a clinical VISA isolate. These preliminary findings provide a rationale for further investigation of this combination in larger collections of clinical isolates and complementary experimental models.

کلیدواژه ها:

Drug repurposing ، Antimicrobial resistance ، Nortriptyline. Staphylococcus aureus ، Vancomycin