NP108, an antimicrobial polymer with activity against methicillin and mupirocin resistant Staphylococcus aureus. [PublishAheadOfPrint]

Staphylococcus aureus is a clinically significant human pathogen that causes infectious diseases ranging from skin and soft tissue infections (SSTI), healthcare associated infections (HAI) to potentially fatal bacteraemia and endocarditis. Nasal carriage of S. aureus, especially persistent carriage, is associated with an increased risk of subsequent infection, particularly nosocomial and surgical site infections (SSI), usually via autoinfection. NP108 is a cationic antimicrobial polymer composed of Generally Recognized as Safe (GRAS) amino acid building blocks. NP108 is broad-spectrum and rapidly bactericidal (3 log kill in ≤3 h); killing bacteria by membrane disruption and cell lysis. NP108, contrary to many antibiotics, shows equally effective antimicrobial activity versus a variety of S. aureus (MIC₁₀₀ = 8 – 500 mg/L) and S. epidermidis (MIC₁₀₀ = 4 - 8 mg/L), whether exponentially growing or in stationary phase. NP108 is antimicrobially active under nutrient limiting conditions similar to those found in the anterior nares (MIC₁₀₀ = 8 mg/L), kills antibiotic resilient small colony variants (MIC₁₀₀ = 32 mg/L)) and S. aureus biofilms (prevention (1 – 4 mg/L) and eradication (>31.25 mg/L)). NP108 is active against isolates of S. aureus resistant to the current standard of care decolonisation agent, mupirocin, with no significant increase in MIC₁₀₀. NP108 is water-soluble and has been formulated into compatible aqueous gel vehicles for human use in which antimicrobial efficacy is retained (2.0% (w/v)). NP108 is a potential non-antibiotic antimicrobial alternative to antibiotics for the nasal decolonisation of S. aureus with clear advantages in its mechanism of action over the existing gold standard mupirocin.

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