Cannabidiol as a Green Adjuvant for Mupirocin-Based Formulations Against Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus

Infections caused by Staphylococcus aureus, particularly methicillin-resistant strains (MRSA), continue to represent a major therapeutic challenge in clinical practice due to their high prevalence and limited treatment options. This study aimed to develop and evaluate an innovative in vitro topical formulation combining cannabidiol (CBD) and mupirocin, exploring its potential synergistic effects against both MRSA and methicillin-sensitive strains (MSSA). A series of assays were conducted, including physicochemical characterization, antibacterial activity tests, minimum inhibitory and bactericidal concentration determinations (MIC/MBC), checkerboard assays, time-kill curves, and biofilm inhibition analyses using crystal violet (CV) and MTT methodologies. The combined formulation demonstrated enhanced antimicrobial efficacy, with synergistic effects confirmed by fractional inhibitory concentration index (FICI ≤ 0.5) and time-kill assays showing ≥ 4 log10 CFU/mL reduction. Moreover, significant decreases in biofilm biomass and metabolic viability were observed. These findings suggest that the CBD–mupirocin formulation holds considerable promise for clinical application in the management of skin infections caused by resistant S. aureus strains.