In vitro and in vivo evaluation of diethyldithiocarbamate with copper ions and its liposomal formulation for the treatment of Staphylococcus aureus and Staphylococcus epidermidis biofilms.

Surgical site infections (SSIs) are mainly caused by () and () biofilms. Biofilms are aggregates of bacteria embedded in a self-produced matrix that offers protection against antibiotics and promotes the spread of antibiotic-resistance in bacteria. Consequently, antibiotic treatment frequently fails, resulting in the need for alternative therapies. The present study describes the efficacy of the Cu(DDC) complex (2:1 M ratio of diethyldithiocarbamate (DDC) and Cu) with additional Cu against and biofilms in models mimicking SSIs and antibacterial activity of a liposomal Cu(DDC) + Cu formulation. The activity on and biofilms grown on two hernia mesh materials and in a wound model was determined by colony forming unit (CFU) counting. Cu-liposomes and Cu(DDC)-liposomes were prepared, and their antibacterial activity was assessed using the alamarBlue assay and CFU counting and using a infection model. The combination of 35 μM DDC and 128 μM Cu inhibited and biofilms on meshes and in a wound infection model. Cu(DDC)-liposomes + free Cu displayed similar antibiofilm activity to free Cu(DDC) + Cu, and significantly increased the survival of -infected larvae. Whilst Cu(DDC) + Cu showed substantial antibiofilm activity against clinically relevant biofilms, its application in mammalian models is limited by solubility. The liposomal Cu(DDC) + Cu formulation showed antibiofilm activity and antibacterial activity and low toxicity in , making it a suitable water-soluble formulation for future application on infected wounds in animal trials.