Abstract and Introduction
Abstract
Objective Drawtex's ability to remove pathogens and associated virulence factors has been demonstrated in vitro. A model of burn wound infection was used to characterize the in vivo impact of this dressing on infection and wound healing.
Methods Paired burn wounds were created on the dorsum of Sprague Dawley rats and were inoculated with methicillin-resistant Staphylococcus aureus (MRSA). Animals were divided into 2 groups, half with wounds that received experimental dressing and the remaining half with control dressing-treated wounds. Dressings remained in place through 3, 6, 9, or 14 days after injury, and methicillin-resistant S aureus and virulence factors were quantified. Laser Doppler imaging was used to examine wound perfusion, and local host immune response was assessed through the quantification of mRNA expression.
Results By day 3, less methicillin-resistant S aureus was measured in wounds treated with experimental-dressing compared to control-dressing wounds. Quantities remained lower in the experimental group through day 14 (P < .001). More methicillin-resistant S aureus was quantified in the experimental dressing itself than in control dressing at all time points (P < .05). Experimental dressing-treated wounds contained less toxic shock syndrome toxin 1 and Panton-Valentine leukocidin than controls (P < .01) on days 6, 9, and 14. Induction of toll-like receptor 2, NOD-like receptor family, pyrin domain containing 3, and interleukin 6 was significantly lower in experimental-dressing treated wounds than in controls on days 6 and 9 (P < .05).
Conclusions The hydroconductive dressing provided a significant reduction in pathogen and virulence factors compared to a control dressing. As a result of clearance of virulence factors from the wound bed, a requisite alteration in host innate immune response was observed.
Introduction
Infection is a significant cause of morbidity and mortality in the hospital setting, and it is an especially relevant factor in the care and treatment of burn-injured patients.[1–3] The burn wound's microenvironment can provide a medium for the growth of pathogenic organisms and for their associated production of virulence factors.[3] Proteinaceous virulence factors produced by many commonly encountered, wound-relevant pathogens can further impede normal wound healing by degrading existing viable tissue. There are many challenges to burn wound healing that may be exacerbated by infection, including burn depth progression, induction of septic shock, and the development of hypertrophic scar.[2–4] Therefore, preventing invasive infection and reducing the load of virulence factors in the wound environment are critical to achieving rapid and complete wound healing and favorable outcomes in these patients.
Methicillin-resistant Staphylococcus aureus (MRSA), one of an increasing number of drug-resistant wound-relevant pathogens, produces virulence factors that have been found to induce shock and sepsis, and enhance bacterial survival. S aureus toxin serotypes include staphylococcal enterotoxin A through SEJ, and toxic shock syndrome toxin 1 (TSST-1).[5] Many of the virulence factors produced by MRSA are categorized as superantigens, which are those exotoxins that have the ability to simultaneously bind both HLA-DR (or DQ) and the T-cell receptor, creating an immunological synapse that can produce inflammatory cytokines at pathologic levels both locally and systemically.[6–10] Toxic shock syndrome toxin 1 is notable for its distinct properties ranging from toxicity induced lethal shock to environmental stability,[11] and is among the most well-studied superantigens. Panton-Valentine leukocidin (PVL) is another virulence factor produced by S aureus, though it is not superantigenic. It is, however, a cytotoxin, and the presence of PVL is associated with increasingly virulent strains of MRSA.[12] S aureus toxins have been shown to interact with nonimmune cells such as epithelial and endothelial cells as well.[13–17]
Many diverse topical agents and dressing products are available to clinicians treating patients with burn wounds. These agents range from ointments and creams to various dressing types, some products impregnated with antimicrobials, and some products without. Because of the prevalence of multidrug-resistant organisms and the risks associated with infection, antimicrobial agents are often preferentially selected over unimpregnated options. Unfortunately, many of the agents used, such as silver, are also known to have some amount of nontarget cytotoxicity that has the potential to impede the healing process.[18,19] The obvious desired outcome for clinicians and patients is rapid and complete burn wound healing, free of complications. It is therefore essential to identify highly effective dressings that decrease infection while also imposing minimal toxicity to the host tissue.
Drawtex is a novel hydroconductive dressing product with a purported ability to remove significant amounts of tissue debris, bacteria, and exudate from wounds.[20–22] It has been approved and indicated for use in a variety of wound types, including complex surgical wounds and burns, and leg, diabetic foot, and pressure ulcers. The dressing contains no antimicrobial chemical agents. A substantial ability (that significantly exceeded that of a comparable, routinely used control dressing) to take up multiple drug-resistant pathogens and associated virulence factors from various media has been previously demonstrated in vitro.[23] Furthermore, in pilot studies, this experimental dressing was observed to reduce both bacteria and virulence factor levels in MRSA-infected burn wounds.[22] While these studies indicate efficacy in decreasing pathogen and virulence factor levels, and therefore, the potential for significant positive outcomes in treating burn wound infections, a controlled in vivo study is needed to make the data translatable and potentially clinically relevant.
The present experiments were designed to further evaluate the efficacy of Drawtex (experimental dressing) as compared to a standard, non–antimicrobial-containing foam dressing (control dressing) in a well-powered in vivo model of burn wound infection. The capabilities of the dressing in removing pathogen and virulence factors from the wounds were examined by quantitative culture and ELISA (enzyme-linked immunosorbent assays). In addition, experimental and control-treated wounds were compared to determine if any changes in pathogen presence resulted in local biologic changes in the host wound tissue relevant to wound healing status. These comparisons were based on wound perfusion and host innate immune response.
ePlasty. 2014;14 © 2014 Open Science Company
