NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus

Abstract

ABSTRACT Staphylococcus aureus is a clinically significant human pathogen that causes infectious diseases ranging from skin and soft tissue infections (SSTI) and health care-associated infections (HAI) to potentially fatal bacteremia and endocarditis. Nasal carriage of S. aureus , especially for 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 against a variety of S. aureus (MIC 100 = 8 to 500 mg/liter) and S. epidermidis (MIC 100 = 4 to 8 mg/liter) isolates, whether exponentially growing or in stationary phase. NP108 is antimicrobially active under nutrient-limiting conditions similar to those found in the anterior nares (MIC 100 = 8 mg/liter) and kills antibiotic-resilient small colony variants (MIC 100 = 32 mg/liter) and S. aureus biofilms (prevention, MIC 100 = 1 to 4 mg/liter; eradication, MIC 100 ≥ 31.25 mg/liter). NP108 is active against isolates of S. aureus resistant to the current standard-of-care decolonization agent, mupirocin, with no significant increase in the MIC 100 . NP108 is water soluble and has been formulated into compatible aqueous gel vehicles for human use in which antimicrobial efficacy is retained (2.0% [wt/vol]). NP108 is a potential nonantibiotic antimicrobial alternative to antibiotics for the nasal decolonization of S. aureus , with clear advantages in its mechanism of action over the existing gold standard, mupirocin.