Topical antimicrobial agents for burn wounds

Topical AntimicrobialAgents for Burn Wounds  Burns  Antimicrobial  Antibiotics Infection  Bacteria  Sepsis Every time a patient receives a burn, it is expected that the burn will be treated using some type of goal of treating these superficial wounds is to opti- ointment or cream. Many physicians know little mize the extent of re-epithelialization to allow the beyond the fact that a burn must be treated using Numerous studies have proved that re-epitheli- alization proceeds more rapidly if the wound changed markedly in the last couple of decades, so topical antimicrobial agents play a different viable wound surface more rapidly if there is no role today than they did in the past. In the past, barrier to interfere with travel. After the wound burns were treated expectantly. Now, burns are dries and forms a scab (made of fibrin, neutrophils, treated more aggressively, using early excision and debris), the epithelial cells must digest this and grafting. This philosophical change must influ- fibrinous exudate using fibrinolytics and proteases ence the topical management of burns. This article to resurface the wound. Because this digestion discusses what role topical agents have in slows epithelial cell migration, the time to healing managing burn wounds. The basics of burn wound is delayed. Any topical agent that maintains a moist healing, how topical agents influence the burn environment allows for more rapid epithelial heal- wound, and the wide variety of different available ing and reduces the chances of scarring. The simplest option, an ointment, maintains the moistenvironment and allows for more rapid healing.
An ointment is a water-in-oil preparation in which the amount of oil exceeds the amount of water in the emulsion. Topical antimicrobial ointments The ultimate goal for all burns is to allow for the such as bacitracin or neomycin maintain a moist wound to heal with the least amount of scarring.
healing environment and are commonly used for The management of the burn wound depends on superficial wounds. These topical ointments need the depth of injury.Each type of burn wound to be washed off and reapplied twice a day, which should have a different management strategy. It is well known that first-degree burns do not requireany form of treatment other than possibly a mois- turizer. Superficial partial-thickness (or second-degree) burns have lost the epidermis but have Deep partial-thickness and full-thickness burns an adequate density of skin adnexa (hair follicles, require different treatment strategies because the sweat and oil glands) to re-epithelialize the wound.
wounds will not re-epithelialize unless they are A partial-thickness burn wound that heals within 2 very small. Deep burns of any size will scar less if to 3 weeks would not be expected to result in they are treated using excision and grafting, so significant scarring. Second-degree burns that the intention when using topical agents is to mini- take longer than 2 to 3 weeks to heal frequently mize bacterial colonization until grafting occurs.
Shriners Hospitals for Children Northern California, Department of Surgery, University of California, Davis,2425 Stockton Boulevard, Sacramento, CA 95817, USAE-mail address: Clin Plastic Surg 36 (2009) 597–606doi:10.1016/j.cps.2009.05.0110094-1298/09/$ – see front matter ª 2009 Published by Elsevier Inc.
Obviously, if the burn is excised and grafted within a destructive threshold or if the bacteria are overly a few days after injury, then there is little coloniza- cytotoxic, then damage to the wound may occur.
tion. Many caregivers will treat these wounds Classically in the burn wound, a bacteria concen- using a broad-spectrum topical cream such as tration of more than per gram of tissue tends silver sulfadiazine to minimize colonization. A to be destructive and lead to impaired graft take, cream is an oil-in-water emulsion in which the whereas a density of fewer than 10per gram of amount of water exceeds the amount of oil. They tissue does little to impair burn wound healing.
are usually water miscible. Agents such as silver All wounds will have some bacterial coloniza- sulfadiazine were originally designed to cover tion. It is not possible to completely eliminate all large third-degree burns for weeks in the era prior organisms from a burn wound. Our bodies are to the adoption of early surgical excisional tech- covered with bacteria that coexist and are in niques. The goal at that time was to minimize many ways beneficial.Elimination of these infection while the eschar spontaneously sepa- commensurate microorganisms allows for the rated. Eschar, the coagulated protein of burned numbers of pathologic organisms to increase.
skin and other tissues, adheres very tightly to the One must always ask if the routine use of antimi- underlying tissue. To separate it from the wound crobial agents is necessary or even harmful. Anti- bed, bacteria must invade the nonviable tissue biotic resistance has become a major problem in and the body must lay down a barrier of granula- our time. Elimination of one population of bacteria tion tissue. The bacteria lyse the nonviable tissue clears the way for a different population. These using proteases. So bacteria must be present for evolutionary forces have led to major resistance spontaneous separation to occur. In the past, it problems related to many pathologic microorgan- was hoped that the patient did not succumb to isms. The rational use of topical and systemic anti- sepsis from bacteria invading the burn wound.
microbial agents should be considered of the Fortunately, this slow and painful process has been replaced by aggressive excision and grafting Because the dominant commensal skin organ- procedures that reduce the patient’s exposure to isms are gram-positive cocci,organisms such inflammatory mediators. Topical agents are now as Streptococcus and Staphylococcus aureus provided during the short time until excision and tend to be early colonizers and infectors of the grafting has been performed. The principal of burn wound. Over time, especially if topical agents aggressive excision and grafting has led to the that act against gram-positive organisms are need for topical antimicrobial agents to minimize used, gram-negative organisms become domi- bacterial colonization at the graft site. Usually, nant. One of the more common gram-negative topical solutions are used for this purpose organisms is Pseudomonas aeruginosa, which because the goal is to reduce the chances for tends to leave a fluorescent yellow/green exudate infection while minimizing toxicity to the stressed on the wound. If gram-negative organisms are controlled, then yeast (Candida) may appearnext. Finally, more resistant bacteria and fungi will invade a wound if the host’s resistance isimpaired and eschar remains on the unhealed To make rational choices concerning the use of topical antimicrobial agents, it is essential to understand how bacteria influence the healing of (MRSA) has emerged as a major cause of burn a wound. One usually assumes that any presence wound infection. Of further concern, multiresistant of bacteria in a wound leads to impaired healing.
gram-negative organisms of the Acinetobacter However, decades ago, researchers applied genus have become a major cause of infection in different types of bacteria on wounds and tested burn units. Previously uncommon fungi such as the tensile strength and time required for closure.
Aspergillus are also being seen more often.
To their surprise, many wounds contaminated Viruses such as Herpes simplex are also a problem with bacteria actually healed faster than nonconta- A recent American Burn Association Consensus Conferenceclassified burn wound infections.
increased, wounds had delayed healing. Contam- Most burn wounds are colonized with bacteria ination with lower numbers of bacteria stimulates and usually produce an exudate that does not an inflammatory response that activates the resi- signify infection.The important clinical signs of dent macrophages to augment healing through a burn wound infection include redness and the release of growth factors and other cytokines.
swelling (typical of streptococcal cellulitis) and discoloration or premature separation of eschar.
Topical Antimicrobial Agents for Burn Wounds Healed donor sites that have their new epithelium Pseudomonas and coliforms), but it has little effect ‘‘melt’’ away may be indicative of ‘‘burn wound on gram-positive organisms because the cell wall impetigo,’’ which is typically a staphylococcal infection. Invasive Pseudomonas infection is man- membrane. Patients may develop hypersensitivity ifested by purple, punched-out lesions in burns or reactions, but absorption across the wound is donor sites, usually accompanied by signs of infrequent. Exposing large surface areas may sepsis or septic shock. Candida infections typi- lead to systemic absorption and expose the cally result in small, white pustules on the skin.
patient to neurotoxicity and renal acute tubular Herpes simplex infections leave punched-out holes (2–3 mm) in previously healing skin. Infec-tions in a skin graft are manifested by graft loss, with purulence being found beneath the original Neomycin is produced by the bacterium Streptmy- graft. When obvious infections occur, systemic ces fradiae and acts like all other aminoglycosides therapy and surgical intervention are indicated, that interrupt protein synthesis by binding to the which are topics not covered in this article.
30S subunit of the bacterial ribosome. It can beprepared as an ointment, cream, or eye drops. It organisms and some limited activity againstgram-positive As stated previously in this article, for more super- tendency for bacteria to develop resistance to ficial burns, the goal of topical agents is to maxi- this antimicrobial agent than to some of the other ointments. There is also a relatively high incidence colonization of pathologic bacteria (). Oint- of hypersensitivity reactions (5%–8%). If large ments maintain a moist environment while acting areas are exposed, there are risks for ototoxicity as a media for antimicrobial agents.
and nephrotoxicity, as there are with all aminogly- cosides. Gentamicin, which is synthesized by Bacitracin is one of the most commonly used Micromonospora purpurea, is a common systemic topical antimicrobial agents for small, superficial aminoglycoside that is available as an ointment or burn wounds. Bacitracin is a mixture of similar a cream. It is difficult to use to regulate systemic cyclic polypeptides produced by a strain of absorption, and it is not recommended for topical Bacillus subtilis. It interferes with dephosphoryla- use. Amikacin, a derivative of kanamycin A, is also tion of a component of the bacterial cell wall. It is available in some countries as a topical aminogly- not an effective oral agent but works well topically.
coside, but should probably be saved for intrave- It is typically placed in a white-petroleum ointment and applied over the wound two or three times per day. The antimicrobial agent is effective againstgram-positive cocci and bacilli and seems to be relatively unlikely to develop resistance to organ- Because many ointments are only effective isms. The topical agent is safe patients of all against gram-positive or gram-negative bacteria, ages. Bacitracin is frequently used for treating many are combined as broader-acting commer- burned faces, which are not amenable to the use cial products. Polysporin (Johnson & Johnson, of silver sulfadiazine or mafenide acetate. The New Brunswick, New Jersey) is a combination of main problem with the agent is that it is not effec- polymyxin B sulfate and bacitracin. Neosporin tive against gram-negative organisms or yeast. It is (Johnson & Johnson) combines three topical not uncommon for people to develop a rash with agents: neomycin, bacitracin, and polymyxin B.
prolonged use, especially on re-epithelialized wounds, which is frequently related to Candida coverage of bacteria, but no clinical trials have overgrowth. The rash resolves quickly after demonstrated their superiority over single agents.
discontinuation of the bacitracin ointment.
Staff members in the units where the author worksoften add other agents to expand the coverage of bacitracin. They add 1 part silver sulfadiazine to 3 Polymyxin B is an antimicrobial agent obtained parts bacitracin to cover gram-positive and gram- from B polymyxa, and it also is placed in a white- negative bacteria. In addition, they mix equal petroleum ointment. It acts as a detergent-like amounts of bacitracin, silver sulfadiazine, and agent that binds to the cell membrane and makes nystatin to cover bacteria and yeast. They usually it more permeable. It is a bactericidal agent apply the ointments using a nonsticky dressing such as Adaptic (Johnson & Johnson) to reduce Table 1A brief listing of currently available topical antimicrobial agents Silver sulfadiazine/cerium nitrate Flammacerium Mafenide/nystatin (Clotrimazole) Formulated in pharmacy 5% Sulfamylon/miconazole powder gram 1, gram –, yeasts 0.25% or 0.5% sodium hypochlorite gram 1, gram –, yeasts, fungi Abbreviations: À, negative; 1, positive.
the possibility of the dressing sticking to the mupiricin to reduce the risk for Staphlococcus infections.There is a potential for developingresistance to the antimicrobial agent, so it should Mupiricin (Bactroban, GlaxoSmithKline, Middle-sex, United Kingdom) has become a popular topical agent since the development of increasing There are other ointments that are less frequently incidence of MRSA infections. Mupiricin is derived used. Povidone-iodine solution is well-known as from a strain of P fluorescens, and it inhibits trans- an antiseptic used to prepare surgical wounds.
fer-RNA activity. It is now the topical treatment of The ointment is available as a topical agent for burns, but is rarely used because of a potential agent is also used intranasally to treat carriers of for toxicity to fibroblasts and keratinocytes. It MRSA. Some burn units are using intranasal has a broad spectrum of activity, covering Topical Antimicrobial Agents for Burn Wounds gram-positive and gram-negative bacteria, yeast, its use in patients who have sulfa allergies. If the and fungi. It can cause contact dermatitis and sulfa allergy is questionable or mild, the author pla- may be tied to metabolic acidosis. There are also ces a small test patch on a nonburned area to reports that the agent may be inactivated by determine if a rash would develop. It rarely causes wound exudates. It should not be used during discomfort and is soothing for most people. Mild pregnancy or in small children, or in any patient cutaneous sensitivities may develop. It may turn who has thyroid disease. In addition, different a gray color, but rarely discolors tissues or clothing formulations of macrolides (erythromycin), quino- (unlike silver nitrate solution). The main downside lones, hydroxyquinolines, tetracyclines, metroni- of the agent is that it has been reported to impair dazole, clindamycin, chloramphenicol, azelaic re-epithelialization, so its use for superficial acid, gramicidin, nitrofurazone, rifaximin, and reta- partial-thickness burns is questionable. The cream pamulin are available but rarely used for burn also has some toxicity to fibroblasts in vitro.
Whether these in vitro activities actually impair There are some topical antimicrobial agents that wound healing is less clear. It also leaves a whitish, are not available in the United States. For instance, yellowish-to-greenish exudate on the wound, fusidic acid, which is derived from the fungus Fusi- which is the caused by the product mixing with dium coccineum, interferes with bacterial protein the serum proteins of the wet scab. This exudate synthesis by preventing the translocation of elon- will lift off when the wound epithelializes, just as gation factor G from the ribosome. Fusidic acid is effective against gram-positive organisms and The classic concern for silver sulfadiazine is for is used in combination with mupiricin for severe a brief leukopenia that occurs 3 to 5 days after Staphylococcus infections. Resistance to the anti- the burn.Although one study suggested that the agent could have some myelosuppressiveactivities,most physicians believe that the dropin white blood cell count is related more to margin- ation of the leukocytes to the wound rather than to Silver sulfadiazine is the most well-known topical always resolves spontaneously, despite continua- agent for the treatment of burns. The cream was tion of treatment using silver sulfadiazine. In addi- introduced in the 1970s and it continues to be tion, the cream is not recommended for faces the most popular cream for the treatment of burns because of the potential for ingestion and eye irri- tation or injury. The sulfonamide component is also associated with kernicterus, so the agent should not be used during pregnancy or in infants.
a mixture of silver nitrate and sodium sulfadiazine.
The silver is complexed to propyleneglycol, stearyl alcohol, and isopropyl myrisolate. The silver atom Mafenide acetate 11.1% cream (Sulfamylon, substitutes for a hydrogen atom in the sulfadiazine Mylan Laboratories, Canonsburg, Pennsylvania) molecule. The original name for this compound is a methylated sulfonamide (sulfa drug) that was Silvadine, but Marion Corporation, the original competes with para-aminobenzoic acid, thus pre- manufacturer, no longer exists. It now comes in venting its incorporation into dihydrofolic acid and several other trade names. Many caregivers auto- blocking normal folic acid metabolism. This action matically treat any burn with this agent. It is the is not typical of other sulfonamides because para- most commonly used topical antimicrobial agent aminobenzoic acid does not antagonize its for superficial and deep burns. It is extremely activity. It is active against gram-positive and popular because it is very soothing and has broad antimicrobial coverage. It is both a sulfa drug and concerns that it may not be as effective for some an agent that slowly elutes silver. It is a bactericidal Staphlococcus strains. It was especially chosen agent that is effective against gram-positive for its efficacy against P aeruginosa, an organism bacteria (eg, Staphlococcus aureus), gram-nega- that used to commonly kill burn patients by tive bacteria (eg, Escherichia coli, Enterobacter, invading the burn wound. It has no activity against Klebsiella, Pseudomonas), and some yeasts (eg, yeast, and thus has a tendency to lead to yeast C albicans) and viruses. The activity of silver as overgrowth in wounds if left for too long. It is an antimicrobial agent in itself will be covered later known for its excellent ability to penetrate tissues such as eschar. This ability has also made it There are minimal problems with silver sulfadia- a favorite topical agent for use in deep ear burns zine, which explains its popularity. One must avoid because it effectively prevents invasive chondritis of the ear. It is prone to cause pain on application and, like other sulfa drugs, can lead to allergic Silver nitrate 0.5% solution is one of the older solu- reactions. The tendency to cause rashes is the tions available for topical treatment of burns and result of allergic tendencies in the patient or to grafts. It covers Staphlococcus species, Pseudo- the agent’s propensity to allow for yeast over- monas, and some yeasts. There are limitations to growth, which can lead to the development of its coverage of other gram-negative bacteria. The small, white papules on the skin. It is classically mechanism of its action is discussed in the later known as a carbonic anhydrase inhibitor, and its section of this article that covers other methods use over large surface areas can lead to metabolic of supplying silver to wounds. Silver ion precipi- acidosis. The metabolic acidosis may lead to tates when it is bound to chloride to form a compensatory increase in respiratory rate to a brownish-black residue that stains the patient’s maintain a normal pH level. Like many topical tissues and anything else it contacts (including creams, the agent inhibits neutrophil and lympho- caregivers and patient’s rooms). After the silver is precipitated, the wound is exposed to water, Approximately 20 years ago, a 5%-solution thus hyponatremia and hypochloremia can result.
Electrolytes should be monitored if large surface commonly used as an antimicrobial solution to areas are treated. Methemoglobinemia is a very reduce infection in skin grafts. The tendency to allow for yeast overgrowth has been dealt withby adding nystatin or miconazole to the solution.
There have been debates as to whether the anti- A genitourinary irrigant that consists of a mixture of fungal properties are as effective in the mafenide neomycin and polymyxin B is available to treat skin acetate solution, but the combination is being grafts, but it is less effective against Pseudomonas used in the author’s units and in many than mafenide acetate solution. In a comparisonstudy reported to the American Burn Association, there were increased wound infections in skin Cerium nitrate has been added to silver sulfadia- grafts when using this agent than when using zine as a commercial product (Flammacerium, a mafenide acetate solution.A variation on this Solvay, Israel) with broad coverage of gram-posi- combination is a triple-antibiotic solution that is a combination of bacitracin (50,000 U), polymixin The combination of the two agents leads to syner- B (200,000 U), and neomycin (40 mg) in 1 liter of gistic activities, at least in vitro. Cerium acts by saline. Again, the downfall of this solution is its interfering with calcium-dependent enzymes, and relative ineffectiveness against Pseudomonas.
it also may affect immune function. It hardens theeschar while still having excellent penetrating abil- ities. Although the product is used in Europe, it is Another very old topical agent is 0.5% or 0.25% not available in the United States. There is some sodium hypochlorite solution (NaOCl, Dakin’s question as to whether it is more effective than solution), which essentially is dilute bleach. There silver sulfadiazine alone. It also has the potential are more dilute concentrations available. The solu- tion has made a return to the author’s unit becauseworkers there have had problems with occasional fungal (Aspergillus or Mucor) invasion in the burnwound. Dakin’s solution has efficacy against Antimicrobial solutions can be used to cover burns bacteria, fungi, and viruses. There are concerns but are more commonly used to provide prophy- about its toxicity to the cells in the healing wound.
laxis to newly applied skin grafts and skin substi- The agent has been reported to dissolve clots and tutes. Solutions are especially useful for meshed grafts because they maintain a moist environment problem has not been noticed in the author’s to optimize epithelialization of the mesh interstices Mafenide acetateMafenide acetate 5% solution was mentioned Acetic acid 0.5% is another antimicrobial solution previously in this article and is commonly used to that is relatively inexpensive and effective against prevent infection, especially Pseudomonas infec- tions in skin grafts. In addition, many centers add including Pseudomonas. This solution is not used very frequently in the United States. Chlorhexidine gluconate solution (0.05% in distilled water) is Topical Antimicrobial Agents for Burn Wounds another agent that has in vitro activity against soluble silver delivered to the wound. In vitro many organisms. The experience with its use for activity frequently does not correlate with in vivo burn wounds is limited. The solution is used as activity because Ag1 usually binds to proteins in a mouthwash to control bacterial numbers. Chlo- the serum or tissues. Delivery of the ion is thus rhexidine gluconate also is usually used as soap very important. Maintenance of a steady level of to wash patient’s wounds and now, when used silver is also very important. In the complex fluids with alcohol, is the preferred preparation for of a wound, silver concentrations of more than central lines. Because it is used as soap and in 50 ppm must be maintained. This is why most preparations, another agent should probably be topical creams are applied twice a day. Eluting used for prolonged contact to minimize the poten- agents, therefore, must have prolonged release The metal form is inert and poorly absorbed by bacterial or mammalian cells. When Ago interacts with cellular fluids and enzymes, it becomes Silver has a long history as an antimicrobial agent, ionized and then is highly reactive, binding to and there are excellent reviews describing the proteins and cell membranes. It may affect cellular history of its use.There are descriptions of permeability and interfere with cell membrane using silver to make water potable from 1000 transport and enzyme activities by interfering with BC, and some accounts state that it was used as protein functions. Like other heavy metals, Ag1 early as 7000 years ago without knowledge of its interacts with thiol groups on the respiratory chain effects. Alexander the Great only drank out of molecules to interfere with cellular energy use.
silver vessels. Silver was used by the Romans as Ag1 interacts with free sulphydryl groups and inter- a medicine. Paracelsus (1493–1541 AD) wrote feres with the enzyme phosphomannose isom- about the benefits of silver as an agent to help erase. The ion also interferes with RNA and DNA healing. Silver nitrate was used to treat fractures, activities. Silver, in itself, has activities against ulcers, and suppurating wounds in the nineteenth bacteria, yeasts, and molds. Ag1 is effective century. German obstetrician K.S.F. Crede intro- against MRSA and vancomycin-resistant entero- duced the use of silver nitrate drops in the eyes cocci if delivered in adequate concentrations.
of newborns to prevent gonorrheal infection in Some of the early uses of silver in the 1970s 1884. The synergistic effects of the combination included using silver-coated fabrics that were con- of silver with low-voltage direct current electricity nected to a direct current of The initial was also recognized soon after the discovery of treatments were for bone infections and appeared electricity. The famous surgeon William Halstead to be effective. Since then, several authors have introduced the use of silver foil as an antimicrobial examined the benefits of treating burn wounds dressing, which was used until antibiotics re- placed it during World War II. Silver has been electrically charged silver cloths has not become used for dental fillings for decades, providing a possible reduction of further dental caries. Silver The most recent fad for topical agents has been is now used in urinary catheters, central lines, the development of dressings that elute silver.
endotracheal tubes, and even in clothing and These products frequently use nanocrystalline shoes to reduce odors from organisms. There silver in the dressing. Nanocrystalline silver is a metastable, high-energy form of elemental silver machines, silver colloids are applied to vegetables prepared by using ‘‘physical vapor deposition in Mexico, and silver is used for water purification.
reactive sputtering,’’ which creates crystals of Whether silver is needed for such products is not oxidized silver (Ag2O and Ag2CO3) and metallic silver. Normally, silver does not dissolve in water, The mechanism of silver’s action is not totally but the nanocrystalline form dissolves to produce clear.All heavy metals are toxic to bacteria 70 ppm of both Ag1 and Ago. A plethora of and other cells. The silver ion (Ag1) is highly reac- silver-eluting products with different delivery tive and binds to negatively charged moieties such methods are now available. These products are as DNA, RNA, negatively charged proteins, and used for different aspects of burn wound care.
other ions. To be biologically active, Ag1 or clus- Many are used for split-thickness donor sites and ters of Ago must be soluble in solution. Ago is the partial-thickness burns. The silver-eluting mate- metallic and uncharged form of silver that is found rials are also used for deeper burns and to provide in crystalline and nanocrystalline forms. In solution antimicrobial coverage over dermal substitutes it must exist in less than eight atom (subcrystalline) such as Integra (Integra, Plainsboro, New Jersey).
groups. Its activity depends on the amount of Even negative-pressure wound-healing devices are starting to use silver in their sponges, such as the GranuFoam Silver sponge (KCI, San Antonio, Nephew, Hull, England) with the healing of another TX), which is effective against vancomycin-resis- wound treated using a non–silver-coated dressing, and there was a significant delay in the healing of donor sites in the wound with the silver-coated develop resistances to silver, but recent evidence concerns for the use of silver-eluting products on mechanisms of how resistance develops are also donor sites. More studies are needed to determine being discovered. The ability of bacteria to if silver has significant effects on healing.
develop resistance to silver is not surprisingbecause they develop resistance to almost all anti- microbials agents. Resistance to silver and many Probably one of the oldest topical agents is honey.
other toxic heavy metals (eg, Cd12, Hg12, Pb12, Reports still indicate that honey is an effective Tl1) is at least in part due to the effects of the genetic machinery. Such resistance genes are paste, probably inhibits bacterial growth because also transferred to other bacteria by plasmids.
of its high osmolarity. Honey inhibits bacterial Resistant organisms develop an efficient efflux growth in vitro, so there may also be some inherent system that ejects Ag1 from the cell (and thus antimicrobial activities. A recent review of the liter- avoids toxicity). Some resistant E coli strains are ature suggests that honey is an effective agent for deficient in outer membrane porin proteins. The burn wounds and may even augment healing. The genes produce different proteins, called sil (eg, studies to support this evidence were not silA, silB), which create a complex set of proteins prospective, randomized studies, but they are, at that eject the silver ion. Other proteins (eg, CusF) are also encoded in the genetic machinery. The Newer agents are being tested all of the time.
resistant genes create at least two silver ‘‘pumps’’ There is a report of a liposomal hydrogel contain- There are some complications from silver use, GmbH & Co, KG, Limburg/Lahn, Germany).
but they are rare. High oral or inhaled doses can There are also reports of a silver sulfadiazine– lead to argyria, which is a permanent deposition impregnated lipidocolloid wound dressing (Urgotol of silver in the skin’s microvessels. This problem SSD, Laboratories Urgo, Chenove, France).A has not been reported with topical use of silver recent publication described the investigation of products. There have been reports of absorption the use of nanofibers in burn wound healing.
of silver from the use of silver sulfadiazine in burns These nanofibers provide a matrix scaffold for over more than 40% of the total body surface area, collagen deposition and have the theoretic advan- so it is conceivable that systemic toxicities could tage of being a delivery system for antimicrobial occur.Silver nitrate solution and, rarely, nano- agents and other healing stimulants (such as crystalline silver products will stain the skin tempo- rarily. The brownish-black precipitate will peel offafter 2 to 3 weeks as the stained epithelium The final concern with silver products is their Topical antimicrobial agents have been used for effects on wound healing.In vitro studies decades to successfully decrease the bacterial have repeatedly demonstrated that silver is toxic load in wounds. Fortunately, early excision and to keratinocytes and fibroblasts. The toxicity grafting of the burn wound has replaced the increases with increased concentrations of silver.
need for prolonged use of these agents. The latest The in vitro inhibition has not led to obvious impair- interest has been in using dressings that deliver ments in animal or human healing. Delivery of silver to the wound. The clinical value of these lower levels of silver in vivo and the binding of newer dressings still needs to be proved clinically.
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