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.

Burn Wound Infections

Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue, cellular, subcellular, and protein levels due to their unusual physicochemical properties (e.g., small size, high surface area to volume ratio, chemical composition, crystallinity, electronic properties, surface structure reactivity and functional groups, inorganic or organic coatings, solubility, shape, and aggregation behavior). Metal NPs, in particular, have received increasing interest due to their widespread medical, consumer, industrial, and military applications. However, as particle size decreases, some metal-based NPs are showing increased toxicity, even if the same material is relatively inert in its bulk form (e.g., Ag, Au, and Cu). NPs also interact with proteins and enzymes within mammalian cells and they can interfere with the antioxidant defense mechanism leading to reactive oxygen species generation, the initiation of an inflammatory response and perturbation and destruction of the mitochondria causing apoptosis or necrosis. As a result, there are many challenges to overcome before we can determine if the benefits outweigh the risks associated with NPs. WIREs Nanomed Nanobiotechnol 2010 2 544–568

For further resources related to this article, please visit the WIREs website

The view presented in this manuscript does not necessarily reflect those of Food and Drug Administration.

/pdf/metal-based-nanoparticles-and-their-toxicity-assessment-3a512ilb5p.pdf

Metal-based nanoparticles and their toxicity assessment.

https://www.eng.tau.ac.il/~meitalz/Articles/E4.pdf

Antibiotic-eluting medical devices for various applications

A range of silver-coated or -impregnated dressings are now commercially available for use but comparative data on their antimicrobial efficacies are limited. The antibacterial activities of five commercially available silver-coated/impregnated dressings were compared against nine common burn-wound pathogens, namely methicillin-sensitive and -resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, Acinetobacter baumannii and a multi-drug-efflux-positive Acinetobacter baumannii (BM4454), using a broth culture method. The rapidity and extent of killing of these pathogens under in vitro conditions were evaluated. All five silver-impregnated dressings investigated exerted bactericidal activity, particularly against Gram-negative bacteria, including Enterobacter species, Proteus species and E. coli. The spectrum and rapidity of action, however, ranged widely for different dressings. Acticoat and Contreet had a broad spectrum of bactericidal activities against both Gram-positive and -negative bacteria. Contreet was characterized by a very rapid bactericidal action and achieved a reduction of > or =10,000 c.f.u. ml(-1) in the first 30 min for Enterobacter cloacae, Proteus vulgaris, Pseudomonas aeruginosa and Acinetobacter baumanii. Other dressings demonstrated a narrower range of bactericidal activities. Understanding the characteristics of these dressings may enable them to be targeted more appropriately according to the specific requirements for use of a particular dressing, as in for prophylaxis in skin grafting or for an infected wound with MRSA.

/pdf/antimicrobial-activities-of-silver-dressings-an-in-vitro-c3j1b5x3t9.pdf

Antimicrobial activities of silver dressings: an in vitro comparison.

Dressings have a part to play in the management of wounds; whether they are sutured or open, usually chronic wounds of many aetiologies which are healing by secondary intention. They traditionally provide a moist wound environment, but this property has been extended through simple to complex, active dressings which can handle excessive exudate, aid in debridement, and promote disorganised, stalled healing. The control of infection remains a major challenge. Inappropriate antibiotic use risks allergy, toxicity and most importantly resistance, which is much reduced by the use of topical antiseptics (such as povidone iodine and chlorhexidine). The definition of what is an antimicrobial and the recognition of infection has proven difficult. Although silver has been recognised for centuries to inhibit infection its use in wound care is relatively recent. Evidence of the efficacy of the growing number of silver dressings in clinical trials, judged by the criteria of the Cochrane Collaboration, is lacking, but there are good indications for the use of silver dressings, to remove or reduce an increasing bioburden in burns and open wounds healing by secondary intention, or to act as a barrier against cross contamination of resistant organisms such as MRSA. More laboratory, and clinical data in particular, are needed to prove the value of the many silver dressings which are now available. Some confusion persists over the measurement of toxicity and antibacterial activity but all dressings provide an antibacterial action, involving several methods of delivery. Nanocrystalline technology appears to give the highest, sustained release of silver to a wound without clear risk of toxicity.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1742-481X.2006.00265.x

Silver dressings: their role in wound management.

The organic salt AgNO3 has been available as a topical armamentarium to the medical arena for centuries and for burns for the past 60 years. Thirty-five (1968) years later, Charles Fox introduced and popularized a new topical agent known as silver sulfadiazine. More recently, several new slow-release silver dressings came to the forefront. Acticoat (Smith & Nephew, Largo, FL) Silverlon (Argentum, Lakemont, GA) & Silvasorb (Medline Industries, Inc, Mundelein, IL). Because the standard of care is to change dressings daily, our study focused in on weekly dressing changes as a cost-containment issue. Sprague-Dawley rats received a standard contact burn (20% TBSA). On day 3, the wound was excised and infected with Pseudomonas aeruginosa and Staphylococcus aureus at 5.0 x 10 cfu/ml. The animals were divided into four groups (n = 5 each group): untreated control, Acticoat group, Silvasorb group, and Silverlon group. The dressings remained on the wounds for 10 days when the wounds were quantitatively assessed. Mean wound counts of the control ranged from 1.2 x 10(5) to 6.5 x 10(5) for P. aeruginosa and S. aureus, respectively. Acticoat dressing counts for both organisms were 0 and 1.8 x 10(3) (median alpha); Silvasorb was 0 and 6.3 x 10(3) and Silverlon was 1.5 x 10(4) x 7.4 x 10(4) (median), Acticoat and Silvasorb were both significantly lower (P < .05) than the control for P. aeruginosa, and Acticoat was significantly lower (P < .05) than the control for S. aureus. Although counts for Silvasorb (M) appear significantly lower than the controls for S. aureus, the numbers were not sufficient to be significant. However, Silverlon did achieve a slight significance. These preliminary data suggest that weekly dressing changes with these new silver dressings are feasible and economically and medically congruous.

Therapeutic efficacy of three silver dressings in an infected animal model.

Originally established in 1977 and revised in 1989, Nathan's Agar Well Diffusion (NAWD) is cur- rently the most successful technique used in evaluating the efficacy of topical antimicrobial agents against various bac- terial isolates of burn wound infections. Methods: In the interest of gathering more up-to-date in- formation, 126 gram-positive and 79 gram-negative bac- terial isolates were tested against the following topical an- timicrobial agents: silver sulfadiazine (1% Silvadene cream, Hoechst/Marion Roussel, Inc.), mafenide acetate (Sul- famylon, Bertex Pharmaceuticals), furacin (Nitrofurazone, Roberts Pharmaceutical Corp), 2% mupirocin (Bactroban, SmithKline Beecham) Polymixin B/Bacitracin (E. Fougera & Co.), Silvadene-Nystatin (1% Silvadene/100,000 U/G Nystatin), Modified Dakins (sodium hypochlorite (NaOCL) 0.025%) and silver nitrate (AgNO 3 ). Using a 6-mm biop- sy punch, Mueller-Hinton agar plates were prepared by "punching out" eight equally spaced wells, and then inoc- ulating with a 0.5 McFarland Standard suspension of each bacterial isolate. The wells were then filled with the top- ical antimicrobial agents and the plates incubated at 37° C for 22 to 24 hours. Susceptibilities were then determined by measuring the zones of inhibition for each topical agent. Results: The data clearly shows that except for Poly B/Bacit and Modified Dakins the remaining six antimicro- bial agents were extremely effective against both the gram- positive and gram-negative isolates. Among them, silver sulfadiazine was 100% effective against the gram-positives (P ≤0.001), and 92.4% effective against the gram-negatives. Mafenide acetate was equally effective against both groups of organisms, at 97% (P≤0.001). Cost assessment reveals that silver sulfadiazine ($72.48 per application) is more cost-effective when used twice daily than mafenide acetate and furacin ($162.40 and $123.74 per application, re- spectively). Furacin, on the other hand, was very effective against the gram-positives. Mupirocin susceptibility for both groups was 88.9% and 91.1%, respectively. The re- sponses to Silvadene-Nystatin and silver nitrate were

Burn Wound Infection Susceptibilities To Topical Agents: The Nathan's Agar Well Diffusion Technique

A novel diphenylbutenoid-type compound from the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr. (Zingiberaceae).

Hepatic stellate cell (HSC) activation via the autophagy pathway is a critical factor in liver fibrogenesis. This study tests the hypothesis that chloroquine (CQ) treatment can prevent autophagy and HSC activation in vitro and in vivo in bile-duct-ligated (BDL) mice. Sham-operated and BDL mice were treated with either PBS or CQ in two 60 mg/kg doses the day (D) before and after surgery. On day 2 (2D), HSCs were isolated, and their biological activities were evaluated by measuring intracellular lipid content, α-sma/collagen, and expression of autophagy lc3, sqstm1/p62 markers. The treatment efficacy on liver function was evaluated with serum albumin, transaminases (AST/ALT), and hepatic histology. Primary HSCs were treated in vitro for 24 h with CQ at 0, 2.5, 5, 10, 30, and 50 µM. Autophagy and HSC activation were assessed after 2D of treatment. CQ treatment improved serum AST/ALT, albumin, and bile duct proliferation in 2D BDL mice. This is associated with a suppression of HSC activation, shown by higher HSC lipid content and collagen I staining, along with the blockage of HSC autophagy indicated by an increase in p62 level and reduction in lc3 staining. CQ 5 µM inhibited autophagy in primary HSCs in vitro by increasing p62 and lc3 accumulation, thereby suppressing their in vitro activation. The autophagy inhibitor CQ reduced HSC activation in vitro and in vivo. CQ improved liver function and reduced liver injury in BDL mice.

/pdf/autophagy-inhibitor-chloroquine-downmodulates-hepatic-1vsqmg90.pdf

Thanh Dang

Papers

Therapeutic efficacy of three silver dressings in an infected animal model.

Burn Wound Infection Susceptibilities To Topical Agents: The Nathan's Agar Well Diffusion Technique

A novel diphenylbutenoid-type compound from the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr. (Zingiberaceae).

Autophagy Inhibitor Chloroquine Downmodulates Hepatic Stellate Cell Activation and Liver Damage in Bile-Duct-Ligated Mice