Hydrogels Embedded With Melittin and Tobramycin Are Effective Against Biofilms in an Animal Wound Model.

We demonstrate that the antimicrobial peptide, melittin, is effective alone and in combination with the aminoglycosides tobramycin to kill growing as biofilms both and . Melittin and tobramycin show enhanced activity in combination at micromolar concentrations, resulting in a 2-log reduction in the number of cells within mature PAO1 biofilms after 6-h of treatment. Alternatively, either agent alone resulted in half-a-log reduction. Time-killing assays demonstrated that the combination of melittin and tobramycin was effective at 2-h whereas tobramycin was not effective until after 6-h of treatment. We also found the combination was more effective than tobramycin alone against biofilms of 7 cystic fibrosis clinical isolates, resulting in a maximum 1.5-log cellular reduction. Additionally, melittin alone was effective at killing biofilms of 4 isolates, resulting in a maximum 2-log cellular reduction. Finally, melittin in combination with tobramycin embedded in an agarose-based hydrogel resulted in a 4-fold reduction in bioluminescent colonizing mouse wounds by 4-h. In contrast, tobramycin or melittin treatment alone did not cause a statistically significant reduction in bioluminescence. These data demonstrate that melittin in combination with tobramycin embedded in a hydrogel is a potential treatment for biofilm-associated wound infections.