BackgroundGalleria mellonella, an advantageous model organism, to investigate the therapeutic potential of bacteriophages. Employing theGalleria mellonella(waxworm) model, this study involved infecting the larvae with pathogenicStaphylococcus aureus, followed by combination treatment with staph phages; vB_Sau_Saa90 and vB_Sau_Saa165 at the concentrations of 107and 109PFU/mL and oxacillin, at 100 mg/kg. The treatment modalities were executed in three distinct orders: pre-phage treatment, simultaneous treatment, and post-phage treatment. Each treatment was administered at 90 min intervals. The health state index of the waxworms was monitored throughout the study.ResultsAmong the three treatment orders, both pre-phage treatment and post-antibiotic treatment exhibited the significant outcomes. The survival percentages ranged from 40% to 50%, 30% to 50%, and 50% to 70% across strong, moderate, and weak biofilm conditions. Notably, the phages vB_Sau_Saa90 and vB_Sau_Saa165 displayed remarkable effectiveness in combination with antibiotics. This successful synergy showcased the potential of combinatorial treatment in effectively addressing biofilm-related infections.ConclusionsThis study holds considerable significance as it underscores the suitability ofG. mellonellaas a model organism for exploring bacteriophage-based therapeutic approaches. The study’s findings shed light on the efficacy of combining bacteriophages and antibiotics to targetS. aureusbiofilm cells. The observed results in the waxworm model highlight a promising avenue for managing biofilm infections. However, the need for further validation through larger animal models is emphasized, as this could potentially pave the way for novel treatment strategies with broader clinical implications.