Epidermicin NI01 demonstrates potent in vivo activity in a murine model of methicillin-resistant Staphylococcus aureus skin infection

Objectives In the UK, over 16% of antibiotic prescriptions are for skin infections. New approaches are required to treat and prevent such infections, and new therapeutic modalities should be investigated. Epidermicin NI01 is a first-in-class bacteriocin with potent activity and a novel mode of action against MRSA and Streptococci, leading causes of community and healthcare acquired skin infections and a significant burden of antimicrobial resistance (AMR). The activity of NI01 in a model of MRSA skin infection was assessed during this study. Methods Immunosuppressed male CD1 mice were wounded dorsally using tape-stripping and S. aureus strain USA300 was topically applied. Topical q24 h administration of vehicle (0.5% HMPC) or NI01 (4 dosing regimens in 0.5% HPMC) or 50 mg of Bactroban 2% (mupirocin) or Fucidin 2% (fusidic acid) was initiated at 24 h post-infection (hpi). At 96 hpi, infected skin was recovered for quantitative skin burden analysis. Results There were no adverse effects observed due to infection or treatment. No reduction in skin burden was seen in the 3% NI01 mono-dose group. Treatments resulted in significant log10 reductions in cfu/g tissue of 2.82 (Fucidin), 2.48 (3% NI01 q24) and 2.47 (Bactroban). The MIC of NI01 for S. aureus strain USA300 was 4 mg/L before the study and ex vivo. Conclusions These in vivo activity data warrant further development of NI01 for topical therapy of infections caused by drug-resistant priority pathogens. Clinical use could spare conventional antibiotics for serious and systemic infections and would support stewardship efforts to reduce mupirocin resistance in S. aureus.