Synergistic and Additive Antibacterial Activity of Biogenic Silver Nanoparticles Combined with Scaptotrigona bipunctata Honey Against Reference and Multidrug-Resistant Bacterial Pathogens

Background/Objectives: Resistance and toxicity limit topical agents for infected burns. We evaluated biogenic silver nanoparticles (bio-AgNPs) combined with Brazilian stingless bee Scaptotrigona bipunctata honey (SB honey). Methods: Bio-AgNPs and honeys from three stingless bee species and Apis mellifera were screened against 11 reference and multidrug-resistant (MDR) strains, including MRSA, MDR Escherichia coli, and MDR Pseudomonas aeruginosa. The most active, SB honey, was combined with bio-AgNPs and assessed by checkerboard (FICI), time-kill, and scanning electron microscopy (SEM). Each agent’s cytotoxicity was determined in HaCaT keratinocytes. Results: Combinations were synergistic (FICI 0.50) against the three Gram-negative strains tested and additive (FICI 0.75) against the three Gram-positive ones, lowering both inhibitory concentrations up to fourfold. The combination reduced viable counts below detection faster than either agent alone at its MBC against MDR P. aeruginosa (30 vs. 60 min) and S. aureus (7 vs. 10–24 h), and matched the fastest single agent against E. coli, at two- to fourfold lower concentrations of both. SEM showed surface damage and incomplete septa. These reduced concentrations fell below each agent’s CC50, increasing the calculated selectivity index. Conclusions: Bio-AgNPs and SB honey act jointly against the reference and MDR strains tested, all associated with burn infections, at concentrations below each agent’s cytotoxic threshold, supporting their further development as a topical antimicrobial.