Acute wounds in healthy patients with low comorbidities will usually progress through the wound healing cascade in a timely manner; however, a delay in healing and subsequent development of a chronic wound requires complex wound assessment and intervention. The changes associated with chronic wound development often involve alterations in one of three primary categories, including systemic and cellular changes, macrovascular or microvascular ischemia, and the negative effects of bacterial bioburden. These challenges highlight the fact that selection of one antimicrobial dressing, or any single therapeutic intervention, will not result in wound healing alone.30 Instead, systemic management of known comorbidities and wound bed preparation are necessary to ready the wound bed for healing.
Sibbald31 et al first described the TIME model for wound bed preparation, which involves removal of devitalized Tissue, reduction of Infection/inflammation, Moisture management, and prevention of Edge rolling or epibole. Therefore, the wound clinician approaches wound bed preparation holistically and determines the amount and type of debridement necessary, the methods by which to reduce bioburden and proinflammatory local wound mediators, the optimal dressings to maintain adequate moisture levels and normothermia, as well as to provide adequate wound filling. Each decision involves an evaluation of the available evidence, professional experience, and the ability of the patient’s resources to obtain and provide the necessary care. Wound care is never straightforward like the testing of a dressing in a laboratory, but instead is a mixture of science and real-world circumstances.
The use of antimicrobial wound care products has received a great deal of scrutiny with some literature suggesting there is no evidence for the use of these products in wound care. However, it is important to understand that the selection of an antimicrobial agent is not meant to bring about wound healing. An antimicrobial dressing may be selected for treatment or palliation in order to
▪ Reduce the bacterial burden of a wound
▪ Decrease pain associated with care
▪ Diminish wound odor
▪ Potentially interrupt bacteria biofilms
A best practice statement32 described this misunderstanding and points out that these misconceptions are related to Cochrane-style systematic reviews, which are devoid of the proper evidence-based usage of antimicrobial dressings, insufficient study follow-up, and unreasonable end points such as time to complete wound healing. Additionally, Sackett33 et al point out that evidence-based medicine is not restricted to RCTs and meta-analysis, but an evaluation of all available external evidence to answer the question at hand. Further, an important potential benefit of antimicrobial dressings is to reduce the use of systemic antibiotic therapy that is prone to bacterial resistance. Landis34 et al states that one in four persons with a chronic wound receives antibiotic therapy at any given time and that over 60% have received these medications in the last 6 months. The overuse and abuse of antibiotics reflects the lack of practitioner knowledge surrounding proper management of complex chronic wounds. With these concepts in mind, it is necessary to examine the levels of bacterial influence in the wound milieu, the products available for bacterial control, and how topical antimicrobial agents can be utilized appropriately.
Infection in humans is generally the result of bacteria, fungi, viruses, or protozoa.35 The term bioburden is utilized in varying connotations to refer to the effect of organisms within a wound bed that influence wound healing. All chronic wounds have some level of bacterial bioburden; however, the presence of bacteria does not indicate infection. In general, clinicians classify the range of bacterial influence using the terms contamination, colonization, critical colonization, and infection (defined in TABLE 13-17). These terms attempt to classify the amount and the activity of the bacteria within the wound. Contamination and colonization do not always require direct intervention and principles of autolytic wound healing are likely sufficient. However, as the wound reaches critical colonization, subtle clinical changes occur that influence the healing trajectory. Infection has occurred if these replicating organisms move from the superficial to the deep tissues, invade tissues not involved with the area of injury, and induce evidence of host injury.34
Table 13-17Classification of Bacterial Burden on a Wound ||Download (.pdf) Table 13-17 Classification of Bacterial Burden on a Wound
|Contamination–the existence of nonreplicating bacteria that does not bring about a host response |
|Colonization—presence of replicating bacteria that have attached superficially without any negative insult to the wound |
|Critical colonization—presence of replicating bacteria that induces a host response and causes subtle clinical changes in the wound and periwound area |
|Infection—movement of the replicating organisms from the superficial to the deep tissues not involved with the area of injury with concurrent evidence of host injury |
Previous studies have attempted to discover the number of bacterial inoculums at which critical colonization occurs, with some sources indicating a level of 105 colony forming units (CFUs) per gram of tissue for some bacterial species; however, this quantification can be misleading. The pivotal concerns include the diversity of bacteria present, the virulence, the presence of a particular species, the expression as planktonic versus biofilm phenotype bacteria, and the host’s immune system ability to resist infection36,37 Authors describe a negative association with bacteria found in chronic wounds and poor wound healing, especially when gram-negative bacteria, proteus, E coli, bacteriodes, β-hemolytic strep, and pseudomonas are present.38 In a study by Dalton et al, pseudomonas was noted to overrun the wound environment, even when only beginning as 1% of the total inoculums; it quickly grew to 100% of the population in 48 hours.39 Similarly, the authors reported that pseudomonas was often found at the leading edge of infection related to both its bactericidal proteases, as well as its superior motility.39 Additionally, its pathogenicity may be more prevalent in certain populations, climates, and developing countries.40 Staphylococcus aureus, on the other hand, is equally pathogenic because it possesses the capability of producing a wide variety of toxins and enzymes with the ability to block phagocytosis, degrade collagen matrices, provide antibiotic resistance, and lyse and destroy host cells, all of which lead to abscess formation.34 While single genera planktonic bacteria are able to induce acute infection, chronic wounds often demonstrate synergistic bacterial relationships, such as those found in mature biofilms, which is discussed later in this section.
The total number of bacteria present is likely irrelevant for the wound care practitioner. First, the number of bacteria cannot be determined by physical assessment and traditional swab cultures are unable to fully identify the vast diversity of organisms. In addition, available laboratory evaluation largely ignores the significance of anaerobes. Newer technologies and methods for identifying a wide range of aerobes and anaerobes are available, such as molecular modeling, which have been found to be far superior to current techniques. Dowd et al41 described a study in which swab culturing found only 12 different bacterial genera, while the same wound revealed up to 106 bacterial genera, most of them facultative anaerobes which are not normally detected with standard approaches. However, these advanced methods remain technically challenging and are not currently available to all clinicians. Because of this, more subtle assessment findings may provide the most beneficial clue as to changes in the wound environment and the detrimental rise in wound bioburden.
Wounds are assessed for etiology, quality and amount of granulation tissue, percentage of nonviable tissue present, condition of the wound edges, presence and amount of exudate, total surface area, and presentation of the surrounding intact skin. While acute infection in a healthy individual displays the classic signs and symptoms of erythema, induration, edema, pain, suppuration, and fever, these findings are often either reduced or absent in the patient with poor perfusion or an incompetent immune system.34 However, the clinician again must utilize keen assessment skills because subtle changes in wound bed appearance may represent alterations in nutrition, inappropriate systemic or local inflammatory states, inadequate perfusion, or medications, all of which may mimic changes seen with an increase in bioburden.
Two pneumonics have been developed to distinguish between critical colonization and infection in a chronic wound. NERDS and STONES provide characteristics that can help differentiate between a wound that has critical colonization (NERDS) and absolute infection of the wound bed and surrounding tissue (STONES). The superficial presence of microbes (NERDS) may be treated with topical antimicrobials since the bacteria are on the surface of the wound bed; however, the deeper infection (STONES) will need to be treated with systemic antibiotics (TABLE 13-18). The differential diagnosis is made clinically; swab cultures may be used to identify the bacteria and determine drug sensitivity.42 Fife et al43 stated that these secondary signs had greater sensitivity than the classic symptoms (0.62 and 0.38, respectively), with increasing pain and wound breakdown often sufficient enough to indicate infection. It is in these circumstances that the authors suggest that early and liberal use of topical antimicrobials may reduce bioburden and localized infections.
Table 13-18Pneumonics for Distinguishing Colonization and Infection in Chronic Wounds ||Download (.pdf) Table 13-18 Pneumonics for Distinguishing Colonization and Infection in Chronic Wounds
Red and bleeding wound surface/granulation tissue
Debris (yellow or black necrotic tissue) on the wound surface
Smell or unpleasant odor from the wound
Size is bigger
Temperature is increased
Osteomyelitis (probe to or exposed bone)
New or satellite areas of breakdown
Exudate, erythema, edema
For years topical application and systemic administration of antibiotics have been utilized because of their bactericidal effects on planktonic bacteria. These mitotically active and vulnerable bacteria can be targeted and killed with the right corresponding antibiotic, antiseptic, or antimicrobial dressing. However, some bacteria and fungi have the capability of inducing a radical change in their phenotype following attachment to the wound surface. These bacteria can express over 800 new proteins within hours, thereby protecting themselves in an extracellular polymeric matrix that provides a protective encasement for a variety of genotypes, with upward of 17 genera of aerobes and anaerobes in each wound.44,45 The bacteria irreversibly attach to the wound surface, become mitotically senescent within the biofilm base, and have enhanced resistance to the host’s antibodies as well as innate phagocytosis. This is described by Phillips46 et al, who explain that resistance is due to limited diffusion of the microbial molecules through a dense and negatively charged matrix, with special bacterial efflux pumps in the cell membranes to pump out antimicrobial agents, with or without the secretion of enzymes that bind or inactivate antimicrobial agents; the lack of a mitotically active base; and areas lacking oxygen that allows for the proliferation of anaerobes (FIGURE 13-42).
Biofilm on a chronic wound The yellow layer on a chronic wound (present more than three years on this patient) is an indication of critical colonization and the presence of biofilm. The film cannot be removed with normal cleansing and requires some type of debridement to remove. Other signs that indicate the presence of biofilm are pain, drainage, and periwound erythema, all a result of the chronic inflammatory state that is caused by the biofilm.
Therefore, the development of this bacterial biofilm results in a chronic state of inflammation for the host, which cannot be removed with the routine use of wound cleansing or antibiotics. In fact, the minimum concentrations of many antibiotics needed to eliminate a biofilm may be thousands of times the standard dose and exceeds the maximum prescription dose available.46,47 While biofilms are microscopic in size, the bedside clinician may suspect the presence of biofilm-encased bacterium in 90% of nonhealing chronic wounds.49,50 Additionally, when the biofilm grows undeterred it may become detectable to the naked eye, such as seen in dental plaque or the development of a dense, slimy membrane.
The inability to remove biofilms through systemic antibiotics and topical antimicrobial therapies highlight the need for repetitive and multimodal debridement.44,50 Both sharp and ultrasonic debridement are often indicated on a twice weekly basis, given the speed at which the biofilm may fragment and resurface the wound bed within 48 hours.51 Debridement serves two major purposes: (1) the physical detachment of the biofilm and its strong adhesion molecules and (2) destruction of the dense outer layer, thus allowing exposure of the bacteria inside the biofilm to antimicrobial agents. Attinger and Wolcott49 describe the clinical significance of this being the ability to combine polymerase chain reaction (PCR) sequencing to direct therapy and select antimicrobials to remove the biofilm from the wound bed.
With specific biofilm-based infections, such as chronic osteomyelitis or prosthetic implant infection, wound healing may not be possible with surface debridement and antimicrobial agents alone. While acute osteomyelitis may be treated and resolve with early identification and antibiotic therapy, recalcitrant osteomyelitis results from poor tissue perfusion that fails to supply antibiotics, as well as biofilm formation. Removal of the infected bone and/or the prosthetic implant is necessary, as described in detail by Roy and colleagues.52 For the bedside clinician, wound assessment with the finding of exposed bone has been shown to have a positive likelihood ratio (LR) of 9.2 for osteomyelitis, and the finding of a jagged feel to the bone when probed has been shown to carry a prevalence of over 60%.53 While imaging studies remain the primary diagnostic, laboratory data including erythrocyte sedimentation rate (ESR) can be used to diagnose osteomyelitis in DFUs, especially when the result is over 70mm/h.53 However, the clinical finding of exposed bone in an open wound indicates the need for more vigilance (FIGURE 13-43A-C).
Wound with osteomyelitis A. The arterial wound on the digit is treated first with revascularization by a stent in the femoral artery. The ischemic wound at this point is suspect for osteomyelitis by the sausage appearance of the toe and palpation of bone in the eschar. Topical antimicrobial dressings are indicated while tests to confirm the diagnosis are planned. B. Two weeks after receiving the stent, the eschar has been debrided and exposed bone is visible, along with loss of the joint stability, resulting in rotation of the distal phalanx. Osteomyelitis has been confirmed and treatment with antibiotics was initiated. C. As a result of the osteomyelitis and the resulting inflammation in the bone, shards of cortical bone have been removed from the open wound with resulting granulation of the soft tissue. The distal phalanx will probably need amputation in order for the patient to fully close and resume wearing adaptive shoes.
Case Study—continued A. The wound after surgical debridement. Initially dressing changes, including the TCC, were performed twice weekly. As the drainage abated, dressings were decreased to weekly. The patient continues to receive hyperbaric oxygen therapy. B. In addition to the TCC and hyperbaric oxygen therapy, selective debridement and bilayered cell therapy dressings were added to the care plan. A contact layer and silver hydrofiber dressing were the secondary dressings. C. Two weeks post-cellular therapy, there is increased granulation, slightly smaller surface area, and less exudate. The film visible over the granulation tissue is sometimes a result of the cell therapy. D. Two weeks after initiation of cellular therapy.
The essential components of treating an acute wound include thorough irrigation, appropriate dressing selection, prevention of infection, assessment for surgical intervention for wound coverage and closure, and off-loading. In the chronic wound, further diagnostic evaluation is indicated, and it should not be assumed that simple wound care is sufficient. If a wound with considerable depth granulates and closes, but then continues to reopen with findings of a sinus track or purulent discharge, surgical intervention is most likely indicated.
Categories and Considerations for Antimicrobial Use
Wound care practitioners have multiple antimicrobial products available for standard care. Six major categories include the following: (1) antibiotics, (2) antimicrobial peptides, (3) antibiofilm agents, (4) antiseptics, (5) disinfectants, and (6) topical antimicrobial dressings.
Antibiotics have decreased in popularity as first-line treatments for management in wound care secondary to the rise of bacterial resistance. While the method of action varies, antibiotics generally have one defined target, thereby limiting their effectiveness against multiple pathogens.54 It is agreed that systemic antibiotics should be avoided without evidence of true clinical infection, and topical antibiotics should be similarly avoided when treating infections because they may cause hypersensitivity reaction, lead to super infections, and encourage resistance.36 Antibiotics should not be abandoned, rather reserved for situations where advancing clinical infection is present, highly virulent organisms exist in the wound bed, or the host’s immune response is severely compromised, such as in DFU infections. The detailed investigation of antibiotic use in wound care is beyond the scope of this chapter.
Two new categories of antimicrobials are entering the wound care market and include antimicrobial peptides (AMPs) and antibiofilm agents. The discovery of AMPs in the 1990s further enhanced understanding of the inflammatory phase of wound healing, offering an additional option to ward off the increase of antibiotic resistance. More importantly, AMPs were found to induce proteoglycan expression and thereby impact keratinocyte migration, angiogenesis, and creation of the ECM.55 These peptides are typically found in polymorphonuclear leukocytes and epithelial cells in eukaryotes and have broad-spectrum bactericidal action against a range of organisms, show rare resistance, and can work in tandem with other antimicrobial agents.36 Clinical trials are underway for a new drug, pexignan,56 which is awaiting FDA approval for use in infected DFUs. Previous studies have already explored the potential constructs from which these peptides could be delivered to the wound bed as well as their potential benefit against resistant organisms.57,58 As of now, these products are not available to the wound care practitioner commercially, but offer hope for improving infection management in the future.
The next product awaiting widespread use in the clinical arena involves a novel antibiofilm/antimicrobial agent, Dispersin B.59 Kaplan et al described the use of exogenously applied deoxyribonucleases on the aggressive adhesion of a biofilm exopolymeric matrix by preventing biofilm formation or by detaching existing biofilms of S aureus and S epidermidis. Moreover, this antibiofilm agent has been combined with triclosan (a broad-spectrum antiseptic) to illustrate synergistic antimicrobial and antibiofilm capability against S aureus, S epidermidis, and E coli. An in vitro study by Darouiche et al60 compared catheters coated with dispersin B plus triclosan against catheters coated with chlorhexidine and silver sulfadiazine and found that the antibiofilm agent more significantly reduced bacterial colonization and demonstrated prolonged antimicrobial activity (p <0.05). This combination has also shown promise in in vitro studies against resistant bacterial biofilms versus currently available topical antimicrobials such as cadexomer iodine and silver gel.61 These in vitro studies warrant the need for increasing in vivo evaluation to determine how these products should be utilized in the future.
Topical antiseptics are antimicrobial agents that reduce the number of microorganisms and may be seen as an adjunct to infection control. Whereas antibiotics have a specific method of action, antiseptics utilize multiple targets to inhibit or kill organisms and have a larger spectrum of activity against bacteria, fungi, and viruses. Categories include alcohols (ethanol), anilides (triclocarban), biguanides (chlorhexidine), bisphenols (triclosan), choline compounds, iodine compounds, silver compounds, peroxygens, and quaternary ammonium compounds.30 These compounds may be in hand soaps, pre-surgical skin preparations, and some wound cleansers. The use of antiseptics in the open wound has previously been viewed with great scrutiny due to the risks of cytotoxicity and the potential for repetitive tissue trauma during their use38; however, this greatly depends on which product is used and more importantly, how it is used by the wound care practitioner. For example, while most experts agree that continuously packing a wound with dressing materials saturated in cytotoxic antiseptics is not appropriate wound care, the short-term use of an antiseptic as part of wound irrigation is often found to be very effective in practice. More importantly, wound care clinicians continue to use antiseptics because of the clinical benefit they see, even if in vitro data do not support their use in all circumstances. Cytotoxic effects can be seen with many approved topicals, including silver, but detrimental effects are generally a result of exposure time and overall concentration.43 Generally, antiseptics are used when the clinician perceives the need to reduce the level of bioburden as the number one priority or visualizes signs of infection. The selected antiseptic is either one with broad-spectrum capability or with a specific effect on a known pathogen, such as acetic acid on pseudomonas.
Antiseptics may also be utilized for specific wounds, such as large total body surface area burns that are prone to detrimental colonization from a variety of organisms that can lead to sepsis, a leading cause of morbidity and mortality. However, guidelines by the US Health and Human Services historically recommend these products not be used in pressure ulcers and suggest alternatives such as normal saline.62 Luckily, compromise can be reached in these differing opinions as newer noncytotoxic antiseptics are available, such as superoxide water solutions (Microsyn, Oculus Innovative Sciences, Petaluma, CA), PHMB irrigations (Protosan, B Braun, Bethlehem, PA), and even diluted and stabilized sodium hypochlorites and hydrochlorous acid (Anasept, Anacapa Technologies, San Dimas, CA; Vashe Therapy, Puricore, Malvern, PA). These products provide the benefits of bioburden reduction without injury to the host cells. A systematic review40 described two small, single-center randomized controlled trials looking at the use of superoxide water versus povidone iodine and soap and water and found that patients with infected DFUs had greater odor reduction, reduction of cellulitis, and improved granulation tissue with the superoxide water solution.
Thus far systematic reviews have failed to identify evidence to recommend one specific cleansing solution or technique for wound management over another.63 However, a best practice statement for the use of topical antiseptics and antimicrobial agents in wound care32 agreed that there are clinically justified circumstances where antiseptics can be utilized for well-defined, short-term time periods, and as part of a wound care plan that involves serial debridement and biofilm prevention and removal strategies. How a wound is irrigated and cleansed needs careful attention, and not just with what it is cleansed. Normal saline is still the most recommended wound irrigation for its ability to remove bacteria from the wound bed. This is not because of its chemical structure; saline is not antimicrobial. Yet when utilized properly, saline is capable of removing bacteria with the right amount of pressure.64 Moreover, Fernandez and Griffiths65 showed that potable water, or tap water, was as effective in wound irrigation as saline and suggest that there is no evidence that it increases risk of infection.
Disinfectants are chemicals that are used primarily to kill microorganisms on surfaces or devices and are an integral part of infection control in medical facilities. They are, however, generally harmful to humans and should not be used topically or in open wounds. While the active agents in these solutions may be familiar to other topical antiseptics, the pH, concentration, and chemical additives warrant that they should never be used for wound care.
Topical-Antimicrobial Wound Dressings
Selection of a wound care dressing is based on far more than reduction of bioburden. The decision and selection is multifactorial, with the clinician asking these questions: How can I dress this wound so as to manage the exudate or moisture level, decrease the frequency of changes, decrease the pain of the patient, decrease the risk of trauma to the wound bed, and adequately pack the dead space? Is an antimicrobial necessary? Can my patient afford these dressings after discharge? In some cases, the antimicrobial selected is related to its known effect against certain pathogens. In other cases, selection is more related to the dressing construct and delivery method of the agent into the wound, and how it manages the other considerations listed above. The decision may be made based on the clinician’s personal experience with a particular agent in the specific wound type that is being assessed. Finally, any patient allergies need to be factored into the selection.
While researchers and companies are scrambling to provide bedside point-of-care testing to guide the bedside clinician with real-time biofeedback to influence the plan of care, much of wound care selection is a mixture of science and art. It is important for the nonclinician or bench researcher to understand that the bedside clinician is not blindly guessing on the plan of care in a laissez-fare fashion. Instead, the wound care practitioner uses keen assessment skills, history and physical assessment, laboratory data, experience, and craftsman-like creativity to improve outcomes. Further, in vitro data are not real world clinical reality, where nonclinical parameters such as availability and affordability also influence practice. According to Gethin,35 dressings should be selected per the specificity and efficacy of the agent, potential cytotoxicity to human cells, effect on resistant bacterial strains, allergenicity, cofactors of the wound based on size and exudate, and total bacterial load.
Current evidence regarding the use of antimicrobials is flawed and leads to erroneous recommendations.66 When studying a topical antimicrobial meant for short-term use, such as silver, looking at its capability to influence time to wound healing is scientifically unsound.32 In the truest form of a randomized controlled trial, one intervention should be investigated until the primary outcome is achieved. However, Gottrup67 describes how this is not possible in wound management secondary to changes in the wound bed that may indicate that the particular intervention is no longer appropriate, multiple modalities are needed, or the healing trajectory is too prominently guided by underlying comorbidities. Further, the author states that the often-used primary outcome of complete wound closure should never be used as a “gold standard” because no therapy could ever be considered efficacious with this parameter. Additionally, no topical antimicrobial has the potential of reducing the systemic contributors to poor wound healing, such as nutrition and disease.35 Many experts agree with these sentiments and add that the majority of systematic reviews looking at antimicrobials have inadequate sample sizes, short follow-up periods, non-random allocation of treatment groups, non-blinded assessment of outcomes, and insufficient delineation between the control and experimental groups.30,32-33,36,67-69
With that in mind, the most commonly used antimicrobials will be evaluated based on their mechanism of action to reduce bacterial bioburden as well as the practical considerations that influence their use.
Silver dressings may be the most popular selection for the reduction of wound bioburden, in large part due to its history. The first reports of silver being used as an antimicrobial agent were in the days of Hippocrates, until it lost favor with the advent of antibiotics during World War II.71 With increasing resistance to antibiotics, silver provides a viable option for the reduction of bioburden and the control of localized infection. One of the major reasons silver is so readily used is because of the wide variety of dressing delivery types that are available. Silver is provided in amorphous hydrogels, sheet hydrogels, alginates, hydrofibers, foams, silicones, contact layers, wound powders, ointments, negative pressure foams, and irrigations in the form of silver nitrate solutions. As described by Mooney et al,71 silver’s broad-spectrum antimicrobial ability is not in question, but the choice of dressing is more dependent on the characteristics of the particular carrier dressing, the way silver is delivered to the wound bed, and the needs of the wound following assessment. An International Consensus Document72 prepared by a group of experts discusses the appropriate use of silver in wound care and describes the function of various silver forms. The document states that the metallic form of silver is unreactive and does not have a bactericidal effect but must ionize to its active form, usually through contact with wound exudate. The silver must either be in contact with the wound bed to kill organisms on the surface or be in an absorbent carrier dressing that will reduce the bioburden by destroying bacteria absorbed into the dressing through the wound exudate. The authors caution the clinician to beware of false claims regarding the amount of silver loaded into a particular dressing as this does not correlate to the amount of silver delivered to the wound bed. The discrepancy is a result of inactivation by levels of wound chloride and proteins.
The benefit of silver is its ability to affect multiple sites within the bacterial cells, such as binding to bacterial cell membranes, interfering with binding proteins and energy production within the cell, decreasing enzyme function, and providing DNA and RNA transcription inhibition.72 The multimodal approach to bacterial death makes silver effective, but also at very low risk to bacterial resistance.73 Additionally, silver may increase the sensitivity of a biofilm to antibiotics as well as alter its adhesion to the wound bed.74
In order to realize its total bactericidal potential, silver must have a controlled and sustained release. In other words, the bacteria must be exposed to a sufficient concentration of silver ions over time without causing tissue toxicity.75 The ability for the dressing to conform, remain in place, and provide consistent coverage of the wound bed is necessary in order to achieve antimicrobial reduction. While silver appears in many dressings, its quantity, chemical form, delivery, release, and ability to conform influence the outcomes observed at the wound site.76,77
Another benefit from silver involves the potential for reducing inflammation. Hoeskstra78 reported a histological comparison between two dressings and showed a reduction in inflammation between the silver hydrofiber group and a tulle gauze control. This finding has similarly been reported in burn management79 and via review of literature by an expert panel.72 It is unclear, however, whether the anti-inflammatory effects of silver are directly related to the resultant reduction in wound bioburden or through some additional unknown mode of action.
Secondary symptoms of wound management are also of importance to the care provider. Dressing construction and function assist with the reduction of pain and trauma to the wound bed during dressing changes. The impact of pain and stress on wound healing is of concern, and dressings capable of delivering silver to the wound bed without adhering to the wound surface are advised in order to decrease pain and prevent trauma to the surface. This will assist in stopping the cycle of repetitive trauma and wound pain, as described by Krasner.80 The use of silicone dressings, especially those impregnated with silver, has become very advantageous for these reasons. When compared to topical silver sulfadiazine, a silver impregnated silicone foam dressing showed a reduction in patient experience of pain at application (p = 0.02) and during wear (p = 0.048), decreased frequency of dressing changes (2.2 vs 12.4), and significantly reduced costs ($309 vs $513) in a multicenter randomized comparative trial.81 The reduction of cost and dressing change frequency was also noted to depend on dressing type in an RCT by Muangman et al.82 However, when levels of silver content and dressing construction type are similar, outcomes may be more comparable, as described in a study looking at silver alginates versus silver carboxymethylcellulose dressings.83
Even when the efficacy of bioburden reduction is similar, secondary symptom control may differ based on dressing type. A study by Glat et al84 showed no statistically significant difference in the rate of infection or time of reepithelialization in partial thickness burn wounds between silver sulfadiazine ointment and a silver hydrogel; however, the author identified less pain and increased patient satisfaction in the hydrogel group. Additional benefits described in RCTs and systematic reviews of silver include odor reduction, decreased wound exudate, and prolonged wear time.69
Despite all of the aforementioned benefits of silver, it is not the dressing of choice for all wounds, nor is it intended to be utilized for the entire duration of the healing process. In fact, the use of silver is recommended for a limited time due to potential apoptosis of keratinocytes, fibroblasts, and leukocytes.85,86 Silver can become cytotoxic to host cells if the dressing delivers large quantities of the ion to the wound and is used over extended periods of time, therefore silver dressings should be discontinued when signs of inflammation and critical colonization have resolved. Symptoms indicative of resolution include improved color and quality of granulation tissue, disappearance of periwound hyperemia, reduction in surrounding erythema, absence of purulence, decrease in pain, and decrease in purulent exudate. Similarly, when new epithelium appears along the wound edge with increasing granulation and contraction of the wound, proliferation should be supported with autolytic moist wound therapy. Most experts suggest a 2-week period of antimicrobial use, at which point the wound should be assessed and the determination made about continuation of current therapy, the need of further wound bed preparation, or the need for a different topical product.32,43,54
Although silver is not indicated for use in wounds that show no evidence of increased bioburden or infection, there are times when prophylaxis may be appropriate. Again, a 2-week window may be considered for patients who are severely immunocompromised, wounds near contaminated areas such as the genitals, wounds with exposed bone, or wounds on extremities with poor circulation.87
Interest has been shown recently in the use of silver dressings to prevent surgical site infection (SSI). SSI may occur within the organ space or as a deep SSI secondary to preoperative or postoperative adherence to prevention guidelines. In these infections, antimicrobial dressings may have little effect when applied topically; however, superficial SSI may also occur, especially in patients with systemic comorbidities that impair wound healing, and thereby increase the risk of deeper tissue infection. While SSIs are multifactorial, an RCT by Siah88 showed a statistically significant difference in the amount of bioburden on postoperative incisions 5 to 7 days after surgery when using nanocrystalline silver compared with control. It is reasonable, therefore, to consider the use of silver dressings for prevention of infection in high-risk patients; however, more research is needed in this area. The NICE guidelines89 found no statistical significance in the type of dressing used when looking at incidence of SSI; however, these dressings were standard dressings without antimicrobial constituents.
The final points of discussion regarding the use of silver involve safety. First, pediatric considerations for care should be considered before selecting silver dressings. A child’s skin is at risk for absorption of topical products leading to systemic toxicity.90 Although silver has been reported in the literature as safe to use in pediatrics,84,91 many studies focused on the end point of wound healing, decrease in pain, or length of stay rather than the risk of harm. The concern for toxicity as seen in in vitro studies has warranted further research in this vulnerable population.92,93 Wang et al94 showed that silver toxicity was a concern when examining pediatric burn patients and the use of nanocrystalline silver dressings. Not only were serum levels elevated, but they were closely proportional to the surface area of the wounds treated. An animal model raised question over deposition of silver in the major organs. In some cases, serum levels of silver have been noted to be 800 times greater than normal.95 Dressings or topical agents providing adult dosages are not suitable for children; however, more research is necessary to determine the amount, length of use, and type of silver dressings that may or may not be safe for the pediatric population. Therefore, the patient’s age, the surface area of the wound, the amount of silver in the dressing, and its delivery are factors to be considered. Silver dressings are not advised for neonates, and the usage of such products in the pediatric population is limited to no more than 2 weeks.54 A product with lower parts per million (ppm) concentration of silver and slow active release from the dressing, instead of high parts per million dressing that actively releases silver ions into the wound bed, are a better selection. These qualities are very product specific and overall caution is advised when considering these products for the pediatric population.
Controversy also exists regarding the use of silver wound dressings on patients having magnetic resonance imaging (MRI) studies. There are true concerns regarding the effect of MRI on medical products as metallic devices should never enter the MRI machine. However, wound care products are often not tested for MRI safety. Because silver is a metallic substance, many manufacturers will often issue warnings regarding its use near MRIs even if no testing has been performed. The concerns are for burns associated with response of the dressing to a magnetic field as well as for image disturbances. At this time, there is no universal recommendation for wound care dressings and MRI; therefore, manufacturer’s recommendations are to be carefully followed. A recent study96 assessed silicone wound dressings with silver (Mepilex AG+ and Mepilex Border AG+, Molnlycke Healthcare, LLC, Norcross, GA) under 3-Tesla and found both dressings to be MRI safe. However, the authors caution that they only tested these two specific dressings, and therefore the results cannot be generalized across all product types. Clinicians are advised to check manufacturer’s recommendations for use before allowing patients to undergo an MRI with silver dressings in place (FIGURE 13-45A-C).
Examples of dressings with silver added as an antimicrobial A. Nanocrystalline silver dressings are a mesh with silver attached to the fibers As the dressing is moistened with either sterile water or exudate, the silver is released to attack the bacteria. In order to be effective, the mesh must be in firm contact with the wound bed and a secondary dressing applied to absorb exudate. Nanocrystalline dressings are also available in a fine mesh that can be fenestrated so that exudate can escape and not collect under the dressing. B. Calcium alginate dressings with silver are indicated for wounds with moderate to heavy exudate. They may also be useful for wounds with friable granulation or a tendency to bleed because of the hemostatic properties of the alginate. C. Foam dressings with silver are indicated for wounds with moderate to heavy exudate. Most dressings with silver have a gray color and are easily distinguished from dressings without silver.
The use of medicinal honey has increased in popularity over the last several years; however, it is by no means the new-kid-on-the-block. The use of various forms of honey dates back thousands of years to the time of Dioscrodies,97 Hippocrates98 and descriptions on medical papyrus from 1325 BC.99 However, the form of medical grade honey used today differs greatly from that of natural or culinary versions. Medical grade honey has two general sources: Leptospermum scoparium (manuka), which is derived from tea plants, and Leptospermum polygalifolium, which is jelly bush honey.100 Both forms have specific qualities related to their processing that affect the bacterial count, pH, enzyme activity, and overall benefit in wound care.
Pieper100 reports that while culinary honey uses heat to prepare the product for consumption, this invariably reduces the enzyme responsible for hydrogen peroxide production, whereas medicinal honey’s gamma radiation sterilization process allows it to retain its biologic activity. This biologic activity is multifactorial and relates to the unique blend of glucose, fructose, sucrose, water, amino acids, vitamins, minerals, and enzymes found in the final product.101 Honey is used for its many capabilities, for example, antimicrobial action, debridement action, anti-inflammatory properties, moist wound maintenance, low pH, and exudate absorption.
Honey is known to be an effective antimicrobial agent. The ability to reduce wound bioburden is directly dependent on the geographical, seasonal, and botanical source, as well as manufacturer processing and storage.102 Honey has been shown to have a polyantimicrobial effect on a broad spectrum of viruses, fungi, protozoa, and over 50 species of bacteria, including organisms such as Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE).36,103 Honey has no risk of bacterial resistance and has been shown to be equal to antibiotics in the prevention of infection following eye surgery102 as well as capable of providing wound healing in pressure ulcers.104 This versatility is enhanced through its availability in many forms, including gels, alginates, hydrocolloids, and solutions.
The antimicrobial action of honey is a result of its ability to kill bacteria, as well as the capacity to regulate biologic activity within the wound. A major benefit is its low pH (3.5-4), which may move a chronic wound from a normally alkaline to an acidic environment, thereby producing a shift in the oxygen-hemoglobin disassociation curve. As described by Gethin,103 this drop in wound pH leads to increased oxygen release, reduced toxicity of bacterial end products, enhanced removal of abnormal wound collagen, decreased protease activity, increased angiogenesis, increased macrophage and fibroblast activity, and enzyme regulation. Further, the biologic activity includes the regulation of the immune response because honey stimulates monocytes to release cytokines, stimulates B and T lymphocytes to activate phagocytes, contributes to therapeutic levels of hydrogen peroxide production, and reduces edema, thereby facilitating improved microcirculation of oxygen and nutrients.100 Although these effects may not be visible, the actions likely explain the experience of seeing honey “jump start” a recalcitrant wound in clinical practice.
One of the major benefits of honey is the ability to both provide bioburden control and enhance debridement at the same time. A study by Gethin and Cowman105 showed that honey was more effective at desloughing wounds with >50% necrotic tissue than standard hydrogel, leading to statistically significant faster healing rates and decreased time to epithelialization. Moreover, the authors state that while sharp and biologic debridement may be faster, honey may be superior to the autolytic or enzymatic debridement seen with hydrogel, collagenase, or cadexomer iodine.
Although the benefits of honey have been described in many studies, there remains conflicting evidence as to where honey fits in best practice. This is largely related to RCTs and Cochrane reviews that have pointed out that honey did not show any significant differences versus standard care, thus questioning its efficacy.106,107 Some studies may limit the potential benefits of honey dressings through the selection of study samples. Often the wounds evaluated are nonnecrotic or without signs of infection and therefore the use of time-to-healing parameters negates the many potential benefits of honey. Additionally, secondary symptoms such as pain, odor, and frequency of changes are not factored in. Rogers and Walker106,107 point out this discrepancy as they do not find sufficient evidence for the use of honey in leg ulcers, pressure ulcers or Fournier gangrene due to lack of available studies; however, they do support honey’s benefit in the management of partial thickness burns. This underlines the need for, as well as the difficulty of, proper research to test honey’s potential methods of action in wound healing.
There are potential adverse effects of using honey. First, stinging or burning pain has been reported after initial application of the dressing to the wound bed, most likely because of the osmotic and pH-lowering action of the dressing. These symptoms will often be transient; however, in some cases they persist and warrant a change in therapy. Unlike silver, Pieper100 describes many studies showing safe and effective use of honey in children, but the author indicates the need to avoid its use in wounds requiring surgical debridement, following incision and drainage of an abscess, or when sensitivity to bee stings is present. While allergy to bee venom is a common fear with the use of honey products, and most clinicians will not select honey with a known bee allergy, no reports of anaphylaxis have currently been described with the use of medicinal honey.108
Honey is increasing in its popularity because of its excellent debridement properties, especially following the lack of availability of papain-based enzymatic debriding agents. Whether the wound is dry or has copious exudate, honey may be utilized with a proper secondary dressing. The osmotic structure of the dressing acts to bathe the wound bed by drawing out peripheral edema in exudative wounds, by adding moisture with the gel form, or by trapping ambient moisture in the hydrocolloid version. Because of this balance, the absorptive alginate version can be used in dry wounds. The alginate may be easier to apply and thus preferable to gel forms that may drip out of the wound in response to gravity. Additionally, because of its theoretical benefits of anti-inflammatory/cytokine-regulating properties, honey may be preferable to a more expensive biologic dressing when treating chronic wounds. However, the actual clinical significance of this has not been tested (FIGURE 13-46A-C).
Honey dressings A. Honey dressings are applied directly onto the wound base and covered with an appropriate secondary dressing. The honey is pliable and conforms to the wound surface without any empty spaces, thus maintaining moisture balance. B. Alginate permeated with honey provides both the properties of honey and the absorbency of alginate fibers. The dressing can be cut into strips for undermining and sinuses, but care must be taken to have the dressing fully in contact with the wound surface. C. Honey in a gel form is not absorbent, but does hydrate a dry wound and aids autolytic debridement. Its viscosity allows the honey to conform to irregular wound surfaces. An absorbent dressing with adhesive borders is recommended to prevent leakage.
Iodine was first discovered by Coutoius in 1811 and it took less than 50 years for it to be utilized in wound care.109 Iodophors were well regarded for their ability to provide both bactericidal and bacteriostatic effects on a broad spectrum of bacterial species. Many iodine preparations exist, but not all are appropriate for wound care secondary to the cytotoxicity that may occur relative to its overall concentration, release, and solubility. Mertz et al110 stated that while iodine has been traditionally seen as an inhibitor of normal wound healing due to results of both in vitro and in vivo toxicity studies, the difference may lie in the components of iodine delivery. For example, povidone iodine includes active agents that improve its solubility and make the solution less damaging to host cells, and thus has been approved by the FDA for short-term use in the treatment of superficial and acute wounds.79 Nevertheless, its interaction with the wound environment results in fast consumption, requiring the clinician to reapply the solution multiple times daily for the full antimicrobial effect.109,110 This results in many undesirable consequences for the wound environment, including the need for frequent dressing changes that negatively affect normothermia; the potential for repetitive, rapid release of large concentrations of iodine into the wound bed; and secondary symptoms such as pain and wound trauma. In other words, iodine in and of itself is not the evil destroyer of the wound bed; however, the beneficial antimicrobial action of iodine needs to be controlled by the speed and amount of its release into the wound bed while maintaining its bactericidal action without inducing cytotoxicity, and it needs to be in a delivery vehicle that allows for less frequent dressing changes.
Cadexomer iodine (CI) solves this dilemma. Available in a paste or sheet dressing, (Iodosorb, Iodoflex, Smith and Nephew, Andover, MA), CI products have a three-dimensional, microspherical shape similar to a whiffle ball, with dextrin-based beads that allow controlled release of 0.9% iodine.109 This structure can be thought of as an exchange system. As wound exudate is absorbed into the dressing, the starch carrier degrades and iodine is released into the wound bed. By doing so, CI has been shown to not inhibit or impair fibroblast function, but is extremely effective in killing broad-spectrum organisms. In fact, Danielsen et al111 looked at the bacteriological efficacy of CI on VLUs colonized with Pseudomonas aeruginosa in an uncontrolled multicenter pilot study. They found that 65% of the wounds had negative cultures for Pseudomonas aeruginosa at 1 week and over 75% had negative cultures at 12 weeks.
In addition to improving wound healing potential by reducing bioburden, multiple researchers have found that CI has the ability to modulate the effects of macrophages to impact cytokine release and to increase growth factor production and activation in the chronic wound.112 Specifically, CI was found to significantly increase the expression of interleukin-1-β, tumor necrosis factor alpha (TNFα), vascular endothelial growth factor (VEGF), and microRNA, thereby enhancing the inflammatory response to support angiogenesis.113 The combination of reducing wound pathogens and directly stimulating a refractory wound underscores the advantages of CI.
As previously discussed, biofilm phenotype bacteria (such as S aureus and P aeruginosa) pose a real threat to wound healing and infection. Almost all topical antimicrobials (including antibiotics, antiseptics, and concentrations of disinfectants) are unable to penetrate the polysaccharide matrix protecting the underlying pathogens. Cadexomer iodine is the exception.109 Recent studies48 investigated the ability for a wide variety of topical antimicrobials to penetrate biofilm inoculated on pigs ears. Of all the topical products tested, only CI was capable of penetrating the matrix and thus impact the bacteria present below the surface. While routine and frequent debridement is still necessary to ensure adequate removal, CI is useful in biofilm-based wound care, or in cases where a biofilm is suspected but aggressive debridement is not possible, for example, on a heavily anticoagulated patient.
Despite these benefits, CI is not without its own contraindications. CI should not be used on patients with a known allergy to iodine, dyes, or shellfish. Additionally, the starch encased structure of CI necessitates an adequate amount of exudate or moisture to stimulate breakdown and release of the iodine. Thus, dry wounds without exudate may not properly activate the dressing. Also, CI negatively interacts with exogenously applied collagenase for debridement; an alternate form of debridement or an alternate antimicrobial agent is required. As with all iodine products, caution is advised for use on children, patients with known thyroid dysfunction, and pregnant or lactating women. In addition, the amount of CI used relative to the size of the wound, the frequency of the application, and overall systemic absorption necessitate caution when considering its use in large surface area wounds, such as burns or surgical incisions (FIGURE 13-47A, B).
Cadexomer iodine dressings A. Cadexomer iodine in paste form is pliable and can be molded to fit and fill most any wound. A secondary dressing sufficient to manage any exudate is required. The iodine is slowly released over a period of approximately 72 hours so that 0.9% concentration is maintained at the wound bed. This concentration is effective against microbes without being cytotoxic. B. Residual iodine on a wound bed at dressing change may have changed color. The active form of iodine is brown, and as the iodine is inactivated (as it destroys bacteria) it becomes iodide which is colorless. This is an indication that all the active iodine has been used and the dressing needs to be changed. When initially used to treat an infected wound, the dressing may need to be changed daily. As the bacteria count decreases, dressings can stay in place longer.
Cadexomer iodine is helpful in preventing a separating surgical incision from progressing to a dehisced incision. A small amount placed on the separation will decrease the bioburden and thereby facilitate reepithelialization of the incision edges.
Polyhexamethylene biguanide (PHMB) has been used for its antimicrobial effects as an environmental disinfectant, swimming pool additive, and contact lens irrigation; however, because of its high biocompatibility PHMB is also used in wound care products. PHMB is described as a heterodisperse mixture of polymers with a structure similar to those found in naturally occurring AMPs and with a similar effect on bacterial cytoplasmic membranes.116 The structure induces cell lysis by its mechanism of attaching and impairing the cell membrane, similar to the mechanism of some antibiotics. It is comparable to its closest chemical cousin chlorhexidine, having similar effects against bacteria such as Pseudomonas aeruginosa, while lacking the potentially damaging chlorobenzene group.117
PHMB is effective on both common wound pathogens and resistant organisms. Cazzinga et al,118 found that PHMB-impregnated foam showed a significant log reduction of Pseudomonas aeruginosa within the wound compared to standard gauze, and did not allow Pseudomonas to colonize the PHMB impregnated foam nor result in a reduction in normal flora. These results support one of the most common uses of PHMB as a preventative barrier dressing against infection in high-risk individuals.
An RCT by Wild et al119 investigated the effect of PHMB delivered by a constantly applied cellulose dressing versus intermittent use of impregnated swabs for the eradication of MRSA in pressure ulcers. Their results showed both applications of PHMB lowered the amount of MRSA present; however, the continuously applied cellulose dressing was more effective with a 100% reduction of MRSA on day 14 versus 67% reduction in the control. Both of these studies highlight the potential benefit of PHMB to reduce bioburden, but also focus on the fact that this substance is not released out of its delivery dressing.
Unlike some silver and iodine dressings, PHMB must be exposed to and in direct contact with the organisms for which it is designed to kill. Hence, once it is bound to a dressing material such as gauze, foam, or alginate, it can only affect bacteria that have been absorbed into the dressing construct.116 In the case of wound irrigations and solutions, time of exposure is the key determinant. Werner and Kramer120 indicate that at least 10 to 15 minutes of exposure is necessary to induce the most antimicrobial effect. Therefore, PHMB in solution form is advised to stay in the wound bed during the cleansing process, or provide the agent as a continuous irrigation, for example, through the use of NPWT with instillation.115
Newer applications of PHMB into biosynthetic cellulose fibers have proven beneficial in managing the problem of PHMB binding as well as the moisture balance of the wound both in dry and wet environments. Biocellulose dressings provide unbound PHMB that is released into the surrounding wound fluid, rendering its antimicrobial action both within the dressing as well as at the wound interface.121,122 The results further demonstrate that the qualities of the dressing may be as important as the antimicrobial agent inside. For biofilm-based wound care, PHMB may be utilized as a method to prevent reattachment of bacteria to the wound bed following debridement, but it is not the frontline choice for biofilm disruption. While a study involving 28 patients by Lenselink and Andriessen123 showed a reduction in biofilm, the presence of biofilm was assumed and not clinically identified. Therefore, the results showing PHMB promoting wound healing via reduction of biofilm in this study must be questioned given the lack of appropriate identification, the small sample size, and the lack of a control group.
PHMB dressings are frequently used to reduce bioburden and secondary symptoms such as wound pain. Many dressing types contain PHMB, including gauzed-based systems (rolled gauze, drain sponges, island dressings, etc), foams, biocellulose dressings, and alginates. Most gauze-based NPWT systems utilize PHMB impregnated roll gauze to provide antimicrobial benefits without the risk of cytotoxicity. The roll gauze is similarly effective in the packing of deep cavity wounds or after trauma when the wound size requires the use of a product with adequate tensile strength and length to prevent the risk of retained foreign bodies. Sibbald et al124 evaluated a PHMB foam dressing in a multicenter, prospective, double-blind RCT utilizing the NERDS and STONEES criteria for bacterial bioburden. They concluded that the PHMB foam significantly reduced bacterial burden compared to standard foam at week 4, as well as reduced wound pain at week 2 and week 4.
PHMB impregnated gauzes should be saturated with normal saline, sterile water, or potable water. Other antiseptic solutions such as sodium hypochlorite may cause a chemical reaction, which inactivates the PHMB and results in a nontoxic yellow stain. Patients with known adverse reactions to PHMB or chlorhexidine are excluded from use. Finally, because of the method of action of PHMB, it is generally recommended that it be used for prophylaxis or on critically colonized wounds, but not as the primary treatment in active wound infections (FIGURE 13-48A, B).116
Polyhexamethylene biguanide (PHMB) dressings A. PHMB, an antimicrobial similar to chlorhexidine (used as a surgical skin prep) without potentially harmful chlorbenzenes, can be impregnated in a variety of delivery dressing products, including gauze, foam, and hydrofibers. The active ingredient must be in contact with the bacteria to be effective, therefore the dressing needs to be in full contact with the wound bed. B. A cellulose dressing containing PHMB is indicated for flat, superficial wounds as either a bacterial barrier for high-risk patients or an antimicrobial primary dressing.
PVA Foam with Gentian Violet and Methylene Blue
The antimicrobial action of methylene blue and gentian violet has long been described in the annals of science.125,126 Possessing both a bactericidal, antifungal and broad-spectrum bacteriostatic effect, these components have been used to treat fungal infections, prevent infection, and assist with bacterial staining in laboratory studies. When combined with polyvinylalcohol (PVA) foam, it becomes a versatile wound care dressing termed methylene blue-gentian violet polyvinyl alcohol foam (MBGV-PVA).This dressing removes exudate from the wound bed while creating singlet oxygen and free radicals that directly impact the plasma membrane causing bacteriolysis.77 Reduction or maintenance of wound bioburden is beneficial; however, the primary clinical advantage of this dressing is the action of its unique foam design. According to testing performed by the manufacturer, the movement of fluids throughout the patented pore design has an effect on the flow rate, which results in a negative pressure-like effect, with recorded pressures of 71.2 mmHg.127 However, the clinical benefit of this claim has not been substantiated. Unfortunately, there is limited to no clinical research available on this product. The benefit is primarily assumed because of the known research on its antimicrobial agents and the physical action of the foam. However, the only available literature regarding its benefit involves case studies and poster presentations, which do not provide the necessary evidence to gauge its use over well-researched antimicrobial products.
Antimicrobials that can be paired with the enzyme collagenase include PVA foam with gentian violet and methylene blue.114
Although clinical research evidence may be lacking, clinical benefit is seen in practice by the effect of MBGV-PVA on decreasing inflammation and pain, reducing fibrin wound covering, improving granulation tissue, and intriguingly, reducing wound edge epibole. These findings have been reported in multiple case series from different authors.128,129 In addition, although products such as antiseptics, silver, and iodine may inhibit the effect of exogenous collagenases used for enzymatic debridement, PVA-MBGV does not.114 This permits combination therapy including reduction of necrotic tissue, entrapment of bacterial endotoxins, and decreased risk for infection.
The PVA foam itself is versatile and capable of being used in a variety of situations. The highly absorptive foam may be used in dry wounds, moist wounds, and excessively exudative wounds when a properly selected secondary dressing is applied. The moist foam will hydrate a dry wound bed when covered with a transparent film, will maintain moisture in a mildly exudative wound, and will achieve maximum absorption in exudative wounds when applied dry. Another benefit of MBGV-PVA foam is the ability to reduce hypergranulation tissue by the removal of excessive moisture from the wound base. Also, as the dressing allows for rapid evaporation of moisture vapor from the foam, it may be used in more creative ways. Since the foam becomes rigid and hard when dry, it can be used to provide antimicrobial protection as well as mild joint splinting, such as in the case of partial thickness burns over the fingers. By applying the dressing after necessary debridement in a moist state, the foam at the wound surface will stay moist enough for autolysis, while becoming rigid to support immobilization of the joint with an appropriate secondary wrap. The dressing can be subsequently rehydrated once daily to maintain a moist wound bed. Additionally, chronic wounds with rolled wound edges (epibole) have been shown to smooth out and elicit epithelialization in recalcitrant wounds.130 Again, the lack of research in these areas questions the actual clinical benefit of this dressing over standard care, but clinical results and its use with debriding enzymes are promising (FIGURE 13-49A, B).
PVA foam with gentian violet and methylene blue A. Polyvinylalcohol (PVA) foam is combined with methylene blue and gentian violet for an absorbent antimicrobial dressing with distinctive versatility. The dressing absorbs exudate and creates an environment for bacteriolysis. The foam is available in both sheets and ropes and can be cut to fit any size wound, undermining, or sinus tract. B. As the foam absorbs drainage and the bacteria are lysed, the foam blanches in color. The foam allows adherence of wound debris, which assists in debridement at dressing changes. Note that the exudate stays in the foam that is in direct contact with the wound bed and does not wick laterally over the periwound skin, thus preventing maceration.
Dialkylcarbamoylchloride (DACC) is a newly discovered antimicrobial dressing. The principles of hydrophobic interaction can be seen in daily life, such as how drops of oil may aggregate into one larger grouping when dropped into water, or how a pathogenic bacteria may grab hold of exposed and damaged collagen in an open wound.131 Microorganisms have the ability to attach to a denatured extracellular matrix through the interaction of their hydrophobic covering with cell surface proteins in the collagen known as hydrophobins.132 This method of surface attachment has been recently harnessed in the form of applying DACC, a naturally occurring hydrophobic fatty acid to various dressing constructs in order to utilize the principles of hydrophobic binding by allowing bandage fibers to stick to the hydrophobic covering of potential microbes in the wound bed.
Dressings containing DACC (Sorbact, BSN Medical, Charlotte, NC), also known generically as pathogen-binding mesh, are not technically antimicrobial, but they have a decided advantage over some of the other products discussed in this chapter—they have no chemical, pharmacological, or antimicrobial agents, thus erasing the concern for bacterial resistance or sensitivity. Silver, iodine, and other antimicrobials utilize multiple pathways to induce bacterial cell lysis (eg, binding to DNA, affecting efflux pumps, disrupting the cell membranes of microbes, denaturing proteins and displacing metallic cations in the bacterial cell wall).77 In all of these cases, the bacteria are killed, and a resulting dump of endotoxins and cellular debris are released into the wound bed. This adds to the inflammatory response, risking the increase in inappropriate polymorphic neutrophil activation of MMPs.133 To avoid these potentially disruptive insults to the wound environment, DACC-covered dressing fibers work instead to bind the microbes to the dressing, render them inactive, and then remove them whole. This concept of repetitive removal of microbes with each dressing change is similar to the concept of sequestration. The principle of trapping and removing bacteria in their intact state is one of the reasons that hydrofibers and alginates are effective in the reduction of wound bioburden.134 In the case of dressings with DACC, however, there is no risk of bacteria re-release from an oversaturated dressing, and the dressing is capable of showing a large log reduction in bacterial load with subsequent dressing changes. A study by Gentili et al135 used real-time PCR evaluations to study the bacterial bioburden in wounds with subsequent changes using DACC-coated dressings. The authors note that the bacterial load at the beginning of wound treatment was 4.41 × 107 per mg of tissue and at the end of therapy 1.73 × 105 per mg of tissue, or a 254-fold reduction in the bacteria present (p = 0.0243).
The ability of the dressing to bind to aerobic bacteria, fungi, and often pathogenic anaerobes is determined by the organism’s cellular surface hydrophobicity (CSH). The expression of CSH is often increased during periods of wound stress or as a result of the colonization of the wound environment.136 This is an important concept when DACC dressings are used for wound care because irrigation must be properly performed and the wound environment assessed for appropriate levels of moisture. Common antiseptics and analgesics have the ability to reduce CSH expression, including eucteric mixture of local anesthetic (EMLA), which can eradicate CSH expression completely.136 If CSH expression falls or is removed, DACC-coated dressings will lose their efficacy. Similarly, principles of hydrophobic binding require moisture to encourage the interaction between two hydrophobic surfaces. Thus, if a wound is dry and nonexudative, moisture may need to be added in the form of a hydrogel or the use of a secondary dressing that traps ambient moisture.137
Other practical considerations for the use of hydrophobic-binding dressings include frequency of wound changes. As the dressings remove bacteria with each change, wounds with clinical signs of critical colonization or infection may require every 12- to 24-hour dressing changes to achieve a necessary reduction in wound bioburden with a concurrent application of an appropriate absorptive secondary dressing to manage exudate.138 In cases of prophylaxis or no clinical signs of infection, a change in frequency of up to 4 days has been described.131 Because of the lack of chemical agents in this dressing, safe use in children has been reported. Meberg and Schoyen139 performed a prospective randomized study on umbilical cord disinfection comparing a group using Sorbact (n = 1,213) with daily cleansing with 0.5% chlorhexidine in 70% ethanol (n = 1,228) and found no differences between the rate of infections in each group. No adverse reactions were reported in the Sorbact group. The versatility of DACC dressings have been evaluated to determine their benefit as wound fillers in NPWT. A pig model was utilized to study the efficacy of pathogen-binding mesh versus foam and gauze as related to granulation tissue formation, wound contraction, microvascular blood flow, and wound contraction.140 The authors found that pressure transduction was similar between all of the products—wound contraction occurred more rapidly with foam products, pathogen-binding mesh showed more rapid granulation tissue formation than gauze and had similar fluid retaining qualities as foam. The adaptable qualities of these products are further supported by the idea that since the dressing is not loading any specific chemical or antimicrobial substance into the wound, the hydrophobic-binding dressings may be used longer than the 2-week challenge period suggested for other antimicrobials.141
The challenge of using hydrophobic DACC dressings is the relative lack of evidence suggesting when these dressings should be selected over traditional antimicrobials. Much of the current literature involves noncomparative, nonrandomized, uncontrolled studies utilizing subjective parameters to assess the benefit of a dressing used in a study population.131 For example, Bruce141 described a multicenter study of six centers across the UK and Ireland that evaluated Sorbact without a comparison group, using subjective assessment of the staff to determine if the dressing had an impact on wound healing, but they did not describe the methods used. A qualitative study of 50 patients was used to assess the efficacy of Sorbact using a questionnaire without description of a control group or methods used.138 In other words, there is insufficient evidence to suggest when a dressing coated with DACC should be selected instead of any of the previously mentioned antimicrobials. It does, however, use a proven method of binding bacteria and appears safe with a low risk of adverse events and no possibility of resistance. Due to the potential versatility of its use, DACC/Sorbact dressings warrant more rigorous comparative examination (FIGURE 13-50A, B).
Dialkylcarbamoylchloride (DACC) A. Dialkylcarbamoylchloride (DACC) is a naturally occurring hydrophobic fatty acid that is attached to the dressing, in this case a nonadherent mesh. The bacteria load is decreased by the binding action of the microbes to the fatty acid on the dressing. The microbes are bound whole, rendered inactive, and removed in entirety with each dressing change. B. Evidence of bacteria, specifically Pseudomonas aeruginosa by the greenish tint, is visible in the secondary dressing over the DACC mesh.
Case Study—conclusion A. Wound after treatment with nanocrystalline silver, before debridement with low-frequency contact debridement. B. Wound bed after debridement with ultrasound. C. Wound with cellular therapy secured with steri-strips. D. Wound after 8 weeks of TCC and collagen matrix dressings to promote healing and reduce proteases. E. After 21 weeks of always changing therapy to meet the needs of the wound as it progressed through healing, the wound is fully epithelialized. Healing will continue as it progresses through the remodeling phase and the tissue regains its tensile strength. The patient was also able to have reconstructive surgery for the Charcot deformity.