Background: Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE) are pathogens associated with mesh infections of hernia patients. Typically, an infection requires mesh removal, as standard medical care frequently fails due to the rise of antibiotic resistance and the formation of biofilms. This urgently calls for new antibacterial strategies.
Aim: To investigate the anti-biofilm activity of the anti-alcoholic drug metabolite diethyldithiocarbamate (DDC) and copper ions (Cu2+) against staphylococci.
Methods: The biofilm killing capacity of DDC and Cu2+ on two hernia mesh materials (polyester and polypropylene) was determined in methicillin-resistant SA (MRSA) and SE via the biofilm attachment assay, followed by CFU counting. Bacterial viability of SA on the meshes was visualised by confocal microscopy using LIVE/DEAD-BacLight staining. To assess synergy of DDC-Cu and antibiotics, checkerboard assays were performed in MRSA biofilm. Cytotoxicity of the compounds was determined in fibroblast cells via the CellTiter-Glo luminescent cell viability assay.
Results: On both mesh types, monotherapy with DDC or Cu2+ showed no significant CFU reduction. The DDC-Cu combination demonstrated extensive biofilm reduction (polypropylene mesh: MRSA: 99.74%; SE: 99.96% biofilm reduction; polyester mesh: MRSA: 96.81%; SE: 99.70% biofilm reduction) compared to untreated meshes, which was further confirmed by confocal microscopy. In MRSA biofilm, DDC-Cu showed synergy and near synergy with fluoroquinolones, tetracyclines, glycopeptides and aminoglycosides and additive effects with β-lactam antibiotics. Over 75% of fibroblast cells remained viable when exposed to DDC, Cu2+ and DDC-Cu over 18 hours.
Conclusion: High antibiofilm activity against staphylococci and low cytotoxicity in fibroblasts highlight DDC-Cu as a potential new treatment strategy for infected hernia meshes. By enhancing multiple antibiotic classes, standard medical care could regain treatment efficacy against antibiotic resistant strains.