Progression Toward Healing: Wound Infection and the Role of an Advanced Silver-containing Hydrofiber(R) Dressing

The Microbiology of Wounds Wound microbiology and healing are unquestionably associated. Wound tissue provides a favorable environment for micro-organisms to grow and multiply, almost inevitably resulting in colonization. Understanding and managing bioburden with appropriate treatments is vital to effective wound healing. In most cases, the micro-organisms that colonize wounds originate from multiple host sources in close proximity to the wound site, such as the mouth, the gut, and the skin. As a result, wounds usually contain unique polymicrobial ecosystems.1 A historically accepted guideline is that a bacterial load greater than 10⁵ colony forming units (cfu)/g of viable wound tissue is an indicator of infection. However, the polymicrobial interactions that take place in this ecosystem are more significant to the development of infection than the mere presence of a specific number or specific types of organisms2 - even well-known pathogenic bacteria such as Staphylococcus aureus or Pseudomonas aeruginosa.3 It is also important to note that both aerobic and anaerobic bacteria may be present within the wound environment. Anaerobes account for 38% of the microbial population in noninfected wounds, increasing to 48% in clinically infected wounds.4 To survive in a wound, micro-organisms must adapt quickly to overcome host immune responses. To this end, they may produce a variety of cell-protecting components, adhesion molecules, enzymes, and toxins. Furthermore, in polymicrobial environments, bacteria can work together to increase their net pathogenic effect, involving processes such as bacterial synergy and quorum sensing (see Figure 1). Synergy may involve aerobic bacteria consuming local tissue oxygen; thus, lowering the oxygen tension and favoring the growth of anaerobes. Similarly, specific nutrients produced by one bacterium may encourage potentially pathogenic cohabitors - for example, production of vitamin K by S. aureus stimulates the growth and pathogenicity of Prevotella melaninogenic.5 Quorum sensing is a process during which populations of organisms utilize specific intercellular communication molecules to help them adapt to changes in environmental conditions.6 In a wound environment, this may involve bacteria producing exopolysaccharide capsules and subsequently biofilms that provide increased protection against the host immune system together with increased production of protease enzymes that facilitates dissemination through tissue. Progression to Infection In a normal situation, the host is in balance with the natural microflora of the skin and mucosal surfaces. A wound represents a disruption in this balance, as the local bacteria opportunistically colonize this new environment and evade the host's immune response. In addition to these exogenous factors, endogenous factors also can affect the likelihood of wound progression. For example, the persistent and elevated inflammatory activity associated with chronic wounds can be associated with underlying pathophysiological conditions such as venous hypertension in the development of venous leg ulcers.7 When the wound bioburden exceeds a host-manageable level, a wound may become infected. This will have a negative impact on patients (eg, increased pain, inconvenience, and illness) and on healthcare providers (eg, increased treatment costs).8 The microbial progression preceding infection is shown as a continuum (see Figure 2). Nonhealing, heavily colonized wounds without clinical signs of infection in which the bioburden is close to or at the maximum level manageable by the host have been described as being critically colonized.9 However, precise transitions between phases are not easy to define; therefore, a diagnosis of infection should be primarily made by assessing clinical signs such as temperature, pain, erythema, malodor, and fever.10 Laboratory microbiological results may be more important in cases where clinical signs of infection are less evident - for example, in diabetic foot ulcers4 or for confirming that empirical antibiotic therapy was appropriate. Passive and Active Mechanisms of Infection Control Appropriate management of infected and critically colonized wounds is essential to encourage wound progression. The aim is to maintain a host-manageable bioburden and to create conditions that are favorable for wound healing. Both passive and active mechanisms can be implemented (see Table 1). Passive approaches to wound management include the use of moisture-retentive dressings. These do not have intrinsic antimicrobial activity, but facilitate effective functioning of the hosts' phagocytic defense mechanisms by creating a moist wound environment.11 Moisture-retentive dressings such as DuoDERM(R) (ConvaTec, a Bristol-Myers Squibb Company, Princeton, NJ) also can act as physical barriers, excluding micro-organisms and particulate contaminants and preventing cross-contamination by wound microflora without leakage when intact. A dressing using Hydrofiber(R) technology (AQUACEL(R), ConvaTec, a Bristol-Myers Squibb Company, Princeton, NJ) also has been shown to effectively absorb and immobilize bacteria within a cohesive gel that forms when the dressing hydrates12 (see Figure 3). This may help maintain a host-manageable bioburden and reduce the risk of cross-infection.12 Additionally, improved average healing rates (2 to 3 days) were seen in protocols of care for partial-thickness wounds covered with moisture-retentive dressings as compared with gauze dressings.13 Active control mechanisms should be considered if passive approaches have been unsuccessful in managing the wound bioburden. They involve using antimicrobial agents that complement host immune activity in reducing wound bioburden and the opportunity for infection (eg, topical agents for indolent, microbially challenged wounds; systemic antibiotics for spreading clinical wound infections). The precise treatment choice will depend on the status of the patient, the nature of the wound, and the pathogenicity of the micro-organisms involved.8 However, differentiating between pathogenic and nonpathogenic species in polymicrobially infected wounds is not possible14; therefore, routine prescription of broad-spectrum antibiotics may be inappropriate or unnecessary and can have negative outcomes. For example, clinician response to the pressure of antibiotic availability could lead to the development of resistant strains of bacteria - a significant concern for healthcare today.8 Systemic antibiotics also may disrupt the balance of the normal host microflora and can increase treatment costs. However, the use of systemic antibiotics is essential for wounds once clinical signs of fulminant infection are evident. Particular care should be taken to target both aerobic and anaerobic bacteria; failure to do so can result in poor clinical outcomes for patients.15 By contrast, topical antimicrobial agents such as ionic silver and iodine rarely select for resistance. These agents have been used traditionally in solution form (eg, silver nitrate solution and povidone iodine solution) to reduce the risk of wound infection, but more recently, these active agents have been made available in dressing and gel forms. Key drawbacks with antimicrobial solutions include a short contact time and the application of high concentrations of the active agent, which increases the risk of toxicity to host tissue. As a result, risk-benefit assessments should be made when using these agents.16 Iodine, in the form of povidone-iodine, is a useful bactericidal agent, although its value in wound antisepsis is subject to debate. Cadexomer iodine is available in a range of concentrations as medicated dressings, solutions, and powders; in such products, slow release from the iodophor is intended to reduce toxicity and optimize activity. Silver-based wound options also have broad-spectrum bactericidal activity and are proven to be effective against antibiotic-resistant bacteria.17 Wound Dressings containing Silver Although many silver-containing wound care products are available, they do not all have equally potent antimicrobial activity (see Figure 4). One reason is that the amount of silver available in different dressings and creams is variable and often uncontrolled. In this author's laboratory studies, a silver concentration of approximately 1 µg/mL (or part per million [ppm]) has been shown to kill a wide range of micro-organisms, including P. aeruginosa (see Figure 4). Delivery of lower concentrations of ionic silver may not be sufficient to maintain activity, and delivery of concentrations above 1 ppm will result in silver ions precipitating with counter ions in wound fluid (notably chloride) to form inactive and minimally soluble salts that will be deposited in (and stain) tissue. However, this has not been found to be a permanent effect with silver-containing dressings.18 Therefore, the effectiveness of ionic silver as an antimicrobial agent and potentiator of wound healing depends on the availability of appropriate concentrations in the wound dressing. AQUACEL(R) Ag (ConvaTec, a Bristol-Myers Squibb Company, Princeton, NJ) is a recently developed absorbent Hydrofiber(R) dressing composed of sodium carboxymethylcellulose and ionic silver with a unique blend of wound management properties. The ionic silver is made available in the dressing at a controlled and sustained rate for up to 14 days, which would be a potential advantage in applications such as burns. In vitro studies have shown that this silver dressing provides antimicrobial activity against a wide range of wound micro-organisms including aerobic, anaerobic, and antibiotic-resistant micro-organisms. The dressing combines antimicrobial action with exudate management and moist wound-healing properties arising from its Hydrofiber(R) technology to support healing. Conclusion A wound provides an ideal environment for colonization by micro-organisms. The polymicrobial ecosystems that ultimately develop are complex. Synergistic interactions between bacteria in a wound can increase their net pathogenic effect. At the same time, competitive interactions between the host immune response and the wound microflora influence the progression of a wound toward healing. Understanding and managing these various interactions is a key factor in optimizing wound care. Infection may develop once the bioburden of the wound exceeds the host-manageable level. In such cases, passive methods of microbial control such as the use of moisture-retentive dressings are likely to be insufficient, and active mechanisms of control should be considered. A silver-containing Hydrofiber(R) wound dressing combines the benefits of exudate management, moist wound healing, and the broad-spectrum antimicrobial properties of ionic silver. The silver ions are delivered to the wound in a controlled and sustained manner and at an effective antimicrobial concentration. This approach has many clinical benefits for the wound healing process.

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