Combined application of Vancomycin and Levofloxacin potentiates the antimicrobial activity against MRSA: a response surface methodology-based study.

Antimicrobial resistance (AMR) ranks among the top 10 global health threats, severely limiting the effectiveness of available therapeutics. methicillin resistant Staphylococcus aureus (MRSA) poses a major concern due to its multidrug resistance and restricted treatment options. The decline in the discovery of new antibiotics has necessitated alternative strategies such as combinatorial applications. The present study described the combined potential of vancomycin and levofloxacin against 10 MRSA strains. Checkerboard assays demonstrated 2 to sixfold and 3 to fivefold reductions in minimum inhibitory concentration (MIC) of vancomycin and levofloxacin, respectively, when used in combination, confirming enhanced antimicrobial potential. Fractional Inhibitory Concentration Index (FICI) also suggested prominent interactions between the selected antibiotics against MRSA when applied together. To further optimize the doses of the combination of the selected antibiotics against MRSA, Response Surface Methodology (RSM) was explored. The RSM models exhibited strong reliability (R2 = 0.9381–0.9903) and non-significant lack of fit (p > 0.05), validating models’ robustness. The optimized combinations were further validated in-vitro through microbial growth profile, suggesting that the actual observations closely aligned with the predicted microbial growth inhibition. Collectively, RSM-optimized doses of vancomycin-levofloxacin could demonstrate enhanced antibacterial potential in combination, offering a rational framework for precision-based therapy against MRSA-borne infections.