Dataset Information

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

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 (MIC₁₀₀ = 8 to 500 mg/liter) and S. epidermidis (MIC₁₀₀ = 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 (MIC₁₀₀ = 8 mg/liter) and kills antibiotic-resilient small colony variants (MIC₁₀₀ = 32 mg/liter) and S. aureus biofilms (prevention, MIC₁₀₀ = 1 to 4 mg/liter; eradication, MIC₁₀₀ ? 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 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% [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.

SUBMITTER: Mercer DK

PROVIDER: S-EPMC5571353 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Mercer Derry K DK Katvars Laura K LK Hewitt Fiona F Smith Daniel W DW Robertson Jennifer J O'Neil Deborah A DA

Antimicrobial agents and chemotherapy 20170824 9

<i>Staphylococcus aureus</i> 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 <i>S. aureus</i>, 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 antimicro ...[more]

PMID: 28607014

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Project description:The chemotherapeutic options for methicillin-resistant Staphylococcus aureus (MRSA) infections are limited. Due to the multiple resistant MRSA, therapeutic failure has occurred frequently, even using antibiotics belonging to different categories in clinical scenarios, very recently. This study aimed to investigate the interactions between 11 antibiotics representing different mechanisms of action against MRSA strains and provide therapeutic strategies for clinical infections. Susceptibilities for MRSA strains were determined by broth microdilution or agar dilution according to CLSI guideline. By grouping with each other, a total of 55 combinations were evaluated. The potential synergism was detected through drug interaction assays and further investigated for time-killing curves and an in vivo neutropenic mouse infection model. A total of six combinations (vancomycin with rifampicin, vancomycin with oxacillin, levofloxacin with oxacillin, gentamycin with oxacillin, clindamycin with oxacillin, and clindamycin with levofloxacin) showed synergistic activity against the MRSA ATCC 43300 strain. However, antibacterial activity against clinical isolate #161402 was only observed when vancomycin combined with oxacillin or rifampicin in time-killing assays. Next, therapeutic effectiveness of vancomycin/oxacillin and vancomycin/rifampicin was verified by an in vivo mouse infection model inoculated with #161402. Further investigations on antimicrobial synergism of vancomycin plus oxacillin and vancomycin plus rifampicin against 113 wild-type MRSA strains were evidenced by combined antibiotic MICs and bacterial growth inhibition and in vitro dynamic killing profiles. In summary, vancomycin/rifampicin and vancomycin/oxacillin are the most potential combinations for clinical MRSA infection upon both in vitro and in vivo tests. Other synergetic combinations of levofloxacin/oxacillin, gentamycin/oxacillin, clindamycin/oxacillin, and clindamycin/fosfomycin are also selected but may need more assessment for further application.

Dataset Information

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

Publications

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

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