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Journal ArticleDOI

Topical Antimicrobials for Burn Wound Infections

01 Jun 2010-Recent Patents on Anti-infective Drug Discovery (RECENT PATENTS ON ANTI-INFECTIVE DRUG DISCOVERY)-Vol. 5, Iss: 2, pp 124-151
TL;DR: This review will cover patented strategies that have been issued or filed with regard to new topical agents, preparations, and methods of combating burn infections.
Abstract: Throughout most of history, serious burns occupying a large percentage of body surface area were an almost certain death sentence because of subsequent infection. A number of factors such as disruption of the skin barrier, ready availability of bacterial nutrients in the burn milieu, destruction of the vascular supply to the burned skin, and systemic disturbances lead to immunosuppression combined together to make burns particularly susceptible to infection. In the 20th century the introduction of antibiotic and antifungal drugs, the use of topical antimicrobials that could be applied to burns, and widespread adoption of early excision and grafting all helped to dramatically increase survival. However the relentless increase in microbial resistance to antibiotics and other antimicrobials has led to a renewed search for alternative approaches to prevent and combat burn infections. This review will cover patented strategies that have been issued or filed with regard to new topical agents, preparations, and methods of combating burn infections. Animal models that are used in preclinical studies are discussed. Various silver preparations (nanocrystalline and slow release) are the mainstay of many approaches but antimicrobial peptides, topical photodynamic therapy, chitosan preparations, new iodine delivery formulations, phage therapy and natural products such as honey and essential oils have all been tested. This active area of research will continue to provide new topical antimicrobials for burns that will battle against growing multi-drug resistance.
Citations
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Journal ArticleDOI
TL;DR: The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing, including biological based approaches and nanotechnology-based wound healing approaches as a revolutionizing area.

307 citations


Cites background or methods from "Topical Antimicrobials for Burn Wou..."

  • ...Most efforts have been conducted to boost the antimicrobial activity of a broad range of topically applied therapeutic agents, facilitating disinfection in wound sites, as well as improving wound healing processes and tissue regeneration mechanisms [7, 8]....

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  • ...The volume of fluid replacement with isotonic crystalloid solution (Ringer’s lactate) can be calculated by the Parkland formula: V(mL) = 4 × body weight(kg) × %TBSA [7, 20]....

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Journal Article
TL;DR: The aim of the study was at assessing whether this material was totally accepted by the host organism and allowed in vivo skin reconstruction of limited area third-degree burns and showed that chitosan materials were well tolerated and promoted a good tissue regeneration.

278 citations

Journal ArticleDOI
TL;DR: A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future.
Abstract: Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future.

209 citations

Journal ArticleDOI
TL;DR: Different approaches to the combination of nanoparticles and PDT have been investigated in relation to the antimicrobial applications of the technique; one use of the nanoparticles is to improve the delivery of photosensitiser to the bacteria; others use the nanop particles to improveThe inactivation kinetics.
Abstract: Photodynamic therapy (PDT) has been proposed as a new technique to inactivate microorganisms as it does not lead to the selection of mutant resistant strains; a clear benefit compared to antibiotic treatment. PDT has also attracted the interest of nanotechnology as the effectiveness of the treatment can be greatly enhanced by the use of nanoparticles. In the last decade, different approaches to the combination of nanoparticles and PDT have been investigated in relation to the antimicrobial applications of the technique. One use of the nanoparticles is to improve the delivery of photosensitiser to the bacteria; others use the nanoparticles to improve the inactivation kinetics. A different approach utilises nanoparticles as a photosensitiser. In this review these diverse types of interactions will be described.

165 citations

Journal ArticleDOI
TL;DR: Data suggest that a dressing combining chitosan acetate with silver leads to improved antimicrobial efficacy against fatal burn infections, as shown by blood culture.
Abstract: Chitosan and nanoparticle silver are both materials with demonstrated antimicrobial properties and have been proposed singly or in combination as constituents of antimicrobial burn dressings. Here, we show that they combine synergistically to inhibit the in vitro growth of Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria (Pseudomonas aeruginosa, Proteus mirabilis, and Acinetobacter baumannii), as judged by bioluminescence monitoring and isobolographic analysis, and also produce synergistic killing after 30 min of incubation, as measured by a CFU assay. The hypothesized explanation involves chitosan-mediated permeabilization of bacterial cells, allowing better penetration of silver ions into the cell. A dressing composed of freeze-dried chitosan acetate incorporating nanoparticle silver was compared with a dressing of chitosan acetate alone in an in vivo burn model infected with bioluminescent P. aeruginosa. The survival rates of mice treated with silver-chitosan or regular chitosan or left untreated were 64.3% (P = 0.0082 versus regular chitosan and P = 0.0003 versus the control), 21.4%, and 0%, respectively. Most of the fatalities occurred between 2 and 5 days postinfection. Silver-chitosan dressings effectively controlled the development of systemic sepsis, as shown by blood culture. These data suggest that a dressing combining chitosan acetate with silver leads to improved antimicrobial efficacy against fatal burn infections.

152 citations


Cites background from "Topical Antimicrobials for Burn Wou..."

  • ...Thus, the search for novel, more efficient antibacterial burn dressings has been the subject of intense and continuing research efforts (14, 20, 27)....

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References
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Journal ArticleDOI
TL;DR: The current review of 129 references describes the biological activity of several chitosan derivatives and the modes of action that have been postulated in the literature.

2,615 citations


"Topical Antimicrobials for Burn Wou..." refers background in this paper

  • ...In common with many polycationic polymers it has pronounced antimicrobial effects due to destabilization of the outer membrane and pemeabilization of the plasma membrane [196]....

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Journal ArticleDOI
TL;DR: All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naive strains, and that bacteria will not readily develop resistance to PDT.
Abstract: Photodynamic therapy (PDT) employs a non-toxic dye, termed a photosensitizer (PS), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. PDT has the advantage of dual selectivity, in that the PS can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. It is known that Gram-(−) bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity in Gram-(+) species, and that PS bearing a cationic charge or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing Gram-(−) organisms. All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naive strains, and that bacteria will not readily develop resistance to PDT. Treatment of localized infections with PDT requires selectivity of the PS for microbes over host cells, delivery of the PS into the infected area and the ability to effectively illuminate the lesion. Recently, there have been reports of PDT used to treat infections in selected animal models and some clinical trials: mainly for viral lesions, but also for acne, gastric infection by Helicobacter pylori and brain abcesses. Possible future clinical applications include infections in wounds and burns, rapidly spreading and intractable soft-tissue infections and abscesses, infections in body cavities such as the mouth, ear, nasal sinus, bladder and stomach, and surface infections of the cornea and skin.

1,728 citations


"Topical Antimicrobials for Burn Wou..." refers background in this paper

  • ...However, in recent years interest in the antimicrobial effects of PDT has revived due to the inexorable increase in drug resistance among many classes of pathogen [182]....

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Journal ArticleDOI
TL;DR: The most important factor governing the outcome of PDT is how the PS interacts with cells in the target tissue or tumor, and the key aspect of this interaction is the subcellular localization of the PS.

1,682 citations

Journal ArticleDOI
TL;DR: Improved outcomes for severely burned patients have been attributed to medical advances in fluid resuscitation, nutritional support, pulmonary and burn wound care, and infection control practices.
Abstract: Burns are one of the most common and devastating forms of trauma. Patients with serious thermal injury require immediate specialized care in order to minimize morbidity and mortality. Significant thermal injuries induce a state of immunosuppression that predisposes burn patients to infectious complications. A current summary of the classifications of burn wound infections, including their diagnosis, treatment, and prevention, is given. Early excision of the eschar has substantially decreased the incidence of invasive burn wound infection and secondary sepsis, but most deaths in severely burn-injured patients are still due to burn wound sepsis or complications due to inhalation injury. Burn patients are also at risk for developing sepsis secondary to pneumonia, catheter-related infections, and suppurative thrombophlebitis. The introduction of silver-impregnated devices (e.g., central lines and Foley urinary catheters) may reduce the incidence of nosocomial infections due to prolonged placement of these devices. Improved outcomes for severely burned patients have been attributed to medical advances in fluid resuscitation, nutritional support, pulmonary and burn wound care, and infection control practices.

1,627 citations


"Topical Antimicrobials for Burn Wou..." refers background in this paper

  • ...Table 1 [7–15] gives a listing of the microbial species responsible for invasive burn wound infection [16]....

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Journal ArticleDOI
01 Mar 2007-Burns
TL;DR: The present review aims at examining all available evidence about effects of silver on wound infection control and on wound healing trying to determine the practical therapeutic balance between antimicrobial activity and cellular toxicity.

1,151 citations