Targeting biofilms of multidrug-resistant bacteria with silver oxynitrate

Abstract

A topical antimicrobial, silver oxynitrate (AgNO), has recently become available that exploits the antimicrobial activity of ionic silver but has enhanced activity because highly oxidised silver atoms are stabilised with oxygen in a unique chemical formulation. The objective of this study was to use a multifaceted approach to characterise the spectrum of antimicrobial and antibiofilm activity of a wound dressing coated with AgNO at a concentration of 0.4 mg Ag/cm. Physiochemical properties that influence efficacy were also evaluated, and AgNO was found to release a high level of Ag ions, including Ag and Ag, without influencing the pH of the medium. Time-kill analysis demonstrated that a panel of multidrug-resistant pathogens isolated from wound specimens remained susceptible to AgNO over a period of 7 days, even with repeated inoculations of 1 × 10 CFU/mL to the dressing. Furthermore, established 72-h-old biofilms of Pseudomonas aeruginosa, Staphylococcus aureus and two carbapenem-resistant Gram-negative bacteria (bla-positive Klebsiella pneumoniae and bla-positive P. aeruginosa) were disrupted and eradicated by AgNO in vitro. AgNO is a proprietary compound that exploits novel Ag chemistry and can be considered a new class of topical antimicrobial agent. Biocompatibility testing has concluded AgNO to be non-toxic for cytotoxicity, acute systemic toxicity, irritation and sensitisation.

Effects of Topical Antimicrobial Formulations on Pseudomonas aeruginosa Biofilm in an In vivo Porcine Burn Wound Model

“…Ionic silver in the form of Ag + is 67 essential for antimicrobial activity and is the most common bioactive silver currently available in 68 a wide range of dressing formats. More recently, the novel silver formulation silver oxynitate, 69 that releases the higher oxidation state silver ions Ag 2+ and Ag 3+ , is hypothesized to have greater 70 bactericidal activity than Ag + because of the higher affinity for electrons, subsequently leading to 71 greater microbial cellular damage (Lemire et al, 2015;Kalan et al, 2017). 72…”

Directed Silica Co-Deposition by Highly Oxidized Silver: Enhanced Stability and Versatility of Silver Oxynitrate

“…Silver oxynitrate has been previously shown to rapidly and effectively eliminate bacterial organisms in both free and biofilm states [16][17][18]. Silicate drug delivery systems, such as silica core-shell systems, may provide an enhanced stability and biocompatibility however, they are also known to modify drug release profiles [3,4].…”

“…Silver oxynitrate is known as a potent antimicrobial agent against planktonic, biofilm, and drug resistant bacterium [16][17][18]. Modification of the form or function of silver oxynitrate may result in an impairment of this antimicrobial activity.…”

“…Recently, higher oxidation states of silver, Ag (II) and Ag (III), have come into light as a viable alternative for these predecessor lower oxidation silvers. Higher oxidation state silver compounds demonstrate superior broad-spectrum antimicrobial efficacy against microbes in planktonic and biofilm states [16][17][18]. Exhibiting marked efficacy against multi-drug resistant bacterium, while remaining safe and not impairing host tissue repair or function [18,19].…”

“…Higher oxidation state silver compounds demonstrate superior broad-spectrum antimicrobial efficacy against microbes in planktonic and biofilm states [16][17][18]. Exhibiting marked efficacy against multi-drug resistant bacterium, while remaining safe and not impairing host tissue repair or function [18,19]. Ag (II) and Ag (III) are strong oxidizing agents with standard electrode potentials of +1.980 V and +1.9 V respectively [20].…”