Ag5IO6: novel antibiofilm activity of a silver compound with application to medical devices

https://doi.org/10.1016/j.ijantimicag.2014.09.008Get rights and content

Highlights

  • Ag5IO6-impregnated wound dressings were compared to seven antimicrobial dressings.

  • Only Ag5IO6 prevented microbial adherence for ≥28 days against all species tested.

  • Only Ag5IO6 eliminated surrounding planktonic microbes for ≥28 days (all species).

  • Only Ag5IO6 generated >4 log reductions against all mature biofilms tested.

  • Ag5IO6 produced total kill in 30 min planktonic log reductions (all species).

Abstract

This work explores the unique antibiofilm activity of pentasilver hexaoxoiodate (Ag5IO6). To test this activity, wound dressings were impregnated with Ag5IO6 and compared with various commercially available silver-containing dressings, as well as dressings containing chlorhexidine, iodine and polyhexamethylene biguanide (PHMB). The materials were tested against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans for their ability to prevent micro-organism adherence, eliminate planktonic micro-organisms and disrupt/eliminate mature biofilms generated using the MBEC™ assay within 24 h of microbial exposure. Only the Ag5IO6-containing dressings were able to prevent adherence and eliminate surrounding planktonic micro-organisms for all species tested for ≥28 days of elution with log reductions >4. Two other silver dressings succeeded against P. aeruginosa only after 28 elution days, whilst the PHMB dressing succeeded after 28 days of elution against C. albicans only. Ag5IO6-containing dressings were able to generate >4 log reductions against all biofilms tested. The only commercial dressings able to generate >4 log reductions against biofilms were iodine against P. aeruginosa and S. aureus, and PHMB against S. aureus. The Ag5IO6 dressings demonstrated complete kill (>4 log reduction) in a standard 30-min planktonic log reduction assay against all species. These results demonstrate that Ag5IO6 has superior activity to a number of antimicrobials, with broad-spectrum efficacy that includes long-term prevention of microbial adherence, rapid kill of planktonic micro-organisms, and the ability to disrupt and eliminate mature biofilms. Thus, Ag5IO6 may be a valuable antimicrobial agent for use in a number of medical device applications, including wound dressings, various catheters or implants.

Introduction

Silver (Ag) has long been known to have antimicrobial properties [1]; however, its use during the twentieth century was limited because of the prevalence of antibiotics and because Ag+ is readily inactivated by contact with Cl (forming the low-activity, poorly-soluble AgCl), proteins and other bodily fluid components [2]. Furthermore, Ag compounds are difficult to incorporate into medical devices with appropriate release rates of active silver species. Recently, numerous new silver compounds/products have been added to medical devices in an effort to overcome these obstacles, mostly as antibiotic alternatives in the face of limited antimicrobial spectrum and growing microbial resistance. However, these silver products have limited antimicrobial activity [3], [4], and even products with excellent activity against planktonic micro-organisms have limited activity against biofilms [5]. Bacteria exist predominantly in biofilms [6]. Biofilms are responsible for 80% of human infections [7] and are typically 100–1000× more resistant to treatment than planktonic micro-organisms [8]. Therefore, when testing new silvers for potential clinical relevance, they need to demonstrate efficacy against biofilm phenotypes.

Ag5IO6 was developed for use in electrochemical cells [9] but, to our knowledge, has not been used as an antimicrobial. Ag5IO6 possesses promising properties for efficacy against biofilms as well as simplicity for coating onto/incorporating into medical devices with appropriate release characteristics. These properties include the presence of silver in both the cation ([Ag3]3+) and the anion, where it is complexed with highly oxidised iodine ([Ag2IO6]3−) [10]. This may enhance penetration of the biofilm relative to Ag+, which binds to negatively charged surfaces of biofilms. The periodate structure around the anionic silver may slow its inactivation by bodily fluid components. Combining silver and iodine may increase antimicrobial mechanisms of action, reducing the likelihood of developing resistance to Ag5IO6. Our synthesis method combines small grain size with large particle size resulting in polycrystallinity on a large surface area, which may improve its antimicrobial activity relative to typical Ag compounds [11]. Ag5IO6 has demonstrated excellent stability (storage; thermal; and in the presence of light, water, saline, organic solvents, autoclaving, ethylene oxide, etc.) and can be easily synthesised with high purity in a form that is simple to deposit onto metals or incorporate into wound dressings, gels, polymers, etc. [12].

This study examined whether Ag5IO6 could prevent biofilm formation on surfaces and eliminate mature biofilms, and compared Ag5IO6 with commercially available antimicrobials to determine whether its activity was novel.

Section snippets

Ag5IO6

Ag5IO6 was synthesised following Nadworny et al. [12]. Product purity was determined via X-ray diffraction to be 100%. Ag5IO6 was coated onto two bandages: a dressing with two outer layers of high-density polyethylene and a rayon/polyester core (3ply-Ag5IO6); and a cotton elastic adhesive bandage [13] (elastic-Ag5IO6), following the method of Olson et al. [14]. Briefly, equivalent dressing quantities were suspended in 1 L of double-distilled water (ddH2O), and 5 g of Ag5IO6 was added with

Anti-adherence

Anti-adherence testing for all dressings over 28 days are shown in Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6 (the full data set is available in Supplementary Tables S2–4, whilst statistical analyses are in Supplementary Tables S5–7). Visually, the iodine lost much of the embedded material with the first saline pre-soak; the dressing is initially a dark brown-orange, and after the pre-soak the saline in the wells had turned this colour, while the dressing was much lighter. The oxysilver

Discussion

Evaluation of antimicrobial coatings on surfaces has been challenging, as coatings that rapidly release antimicrobial agents are frequently ineffective in vivo due to active agent being lost to the environment. Traditional assays such as zone of inhibitions are poor predictors of the capability of medical devices to prevent biofilm formation when in place for >24 h [2], [3]. The anti-adherence test described was developed in-house to test coatings that are slow release and/or remain active for

Acknowledgments

K. Unrau, Y. Cabrera, T. Thiessen, A. Miller, Z. Zheng, A. Alemka, B. Buziak and B. Barth are acknowledged for their technical help.

Funding: PN and VI were supported by Alberta Innovates Technology Futures (AITF) as r&D Associates. This work was supported by BioAlberta Medical Product Development Program (MPDP). AITF and MPDP had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the manuscript, and in the decision to submit the manuscript for

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    Present address: School of Biomedical Engineering, McMaster University, 4th Floor Engineering Technology Building (ETB), 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.

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