BURN WOUND INFECTION BURN WOUND INFECTION Skin is

BURN WOUND INFECTION

BURN WOUND INFECTION • Skin is the first immune defense mechanism and functions as a barrier against microorganisms • Infections are a significant problem once open wounds compromise this barrier

BURN WOUND INFECTION • the four leading causes of burn morbidity are: • (1) pneumonia, • (2) cellulitis, • (3) urinary tract infections, (4) burn wound infections

BURN WOUND INFECTION • A cutaneous burn is initially sterile as commensal skin flora are killed with the skin in thermal event. • Unfortunately the burn wound provides optimal bacterial growth conditions due to a reduced blood supply and a nutrient-rich environment, leading to rapid wound colonization

BURN WOUND INFECTION wound colonization : • (1) low concentrations of bacteria on the wound surface, • (2) absence of invasive infection, • (3) less than 10⁵ organisms per gram tissue

BURN WOUND INFECTION • In a superficial burn, skin flora can survive in hair follicles and sebaceous glands in the same manner as keratinocytes to repopulate a physiological microbiome • However, burns are customarily colonized by pathogens from the environment, the patient’s gut, or the naso-oropharyngeal tract.

BURN WOUND INFECTION • bacteria double 2– 3 times per hour • consequently a single bacterium can become 10 million in 1 day • Therefore colonization can quickly become an infection capable of converting partial-thickness into full-thickness burns by causing vessel thrombosis and necrosis in viable tissues in the wound penumbra

• Gram-positive bacteria tend to colonize an affected area first, • with subsequent colonization by gram-negative bacteria • Delayed treatment risks colonization by extended-spectrum pathogens, bloodstream invasion, and the development of sepsis, all of which increase the likelihood of death.

• Early wound excision eliminates the devitalized tissue that is the main reservoir for pathogen nourishment and habitat. • Prompt autografting reestablishes skin barrier function and denies pathogens access to the host

• Assiduous washing technique allows 2 -log , reduction in colony counts, breaks down and removes biofilms, and purges the devitalized tissue that pathogens thrive upon • Systemic antimicrobials kill and suppress the invading pathogens accessing perfused areas of tissue

TREATMENT OF BURN WOUND INFECTIONS • Treatment of burn wound infections is multimodal: • Surgical débridement and assiduous washing technique decrease the bacterial and nutritive burden • Aggressive grafting denies the pathogens wound surface area to colonize and infect. • Topical antimicrobial compounds reduce pathogen burden in the wound and periwound areas while allowing skin grafts to proliferate and cover the wound.

TREATMENT OF BURN WOUND INFECTIONS ØTopical antimicrobial compounds reduce pathogen burden in the wound and periwound areas while allowing skin grafts to proliferate and cover the wound. ØSystemic antimicrobials are administered to treat invasive pathogens and prevent or reduce the systemic spread of infection

TOPICAL ANTIMICROBIAL COMPOUNDS • significantly reduced burn mortality • However, no single agent is entirely effective. • Each possesses its own spectrum, advantages, and disadvantages. • Wounds may be dressed with any topical agent when quantitative culture counts persist at less than 10²/g tissue.

TOPICAL ANTIMICROBIAL COMPOUNDS • Topical antimicrobial agents fall into five major classes, • each possessing different antimicrobial spectra, duration of action, penetration, and toxicities

TOPICAL ANTIMICROBIAL COMPOUNDS • Soaps are the first form of topical antimicrobial and are employed during washing. • They are effective in disrupting biofilms and washing pathogens from the patient • Biofilms are coherent clusters of bacterial cells embedded in a biopolymer matrix that, compared with planktonic cells, resist host defenses and show increased tolerance to topically (antiseptics) and systemically (antibiotics) administered antimicrobials, thus creating the perfect environment

TOPICAL ANTIMICROBIAL COMPOUNDS • Biofilm bacteria are extremely difficult to remove, requiring surgical or sharp instruments and/ or mechanical wound débridement and washing with soap and water. • washing burn wounds with soap and water using assiduous washing techniques can cause a 2 -log reduction in bacterial counts over 48 hours, improving autograft take by infected wounds.

TOPICAL ANTIMICROBIAL COMPOUNDS • According to recent recommendations wounds not associated with clinical signs or symptoms of infection yet suspected of having biofilm should be treated with débridement, antimicrobial dressings, antiseptic soaks, and thorough cleansing with antiseptic products to prevent bacterial growth

• Many oxidative halides are used as topical antimicrobials. • Classically sodium hypochlorite (Dakin’s solution) has been employed due to its broad bactericidal range and effective dissolution of biofilms • full-strength to be tissue toxic, as are the pharmacy-available half- and quarter-strength Dakin’s solutions, though they are effective antimicrobials

• Na. OCl at a concentration of 0. 025%, or one-twentieth Dakin’s. Buffered onetwentieth Dakin’s was formulated to mimic normal human physiologic parameters, with the added benefits that it is a broad-spectrum antiseptic, yet nontoxic to fibroblasts nor inhibiting of wound healing. It is bactericidal against P. aeruginosa, S. aureus, methicillin-resistant staphylococci, enterococci, and other gram-negative and gram-positive organisms, and it may be used separately or in combination with other agents

• oxychlorosene (Clorpactin) to allow longer tissue half-life, neutral p. H, and lower tissue toxicity. • It is used intravesicularly and intrarenally to control hemorrhage in genitourinary cancer cases and has been recently resurging as a topical antimicrobial.

• Povidone-iodine (Betadine) is another halide used as a topical antimicrobial; it is available as a liquid or an ointment in varying concentrations. It has a broad -spectrum of activity, covering gram-positive and gram-negative bacteria, yeast, and fungi. • Topical application of this agent can be painful. The iodine component of this topical agent may be absorbed more extensively in burn wounds, resulting in iodine toxicity, renal failure, acidosis, and dermatitis (in intact skin). Furthermore povidone-iodine is cytotoxic to fibroblasts and keratinocytes

• Acetic acid, also called ethanoic acid or vinegar, is a colorless topical agent used as a disinfectant for skin and soft tissue infections. It is effective against gram-negative bacteria, especially P. aeruginosa. Its clinical antibacterial efficacy requires a minimu concentration of 0. 5%. • acetic acid is toxic to fibroblasts and substantially decreases cell viability, effects that increase with the concentration

• Silver ions are a common topical heavy metal antimicrobial. • Silver is delivered as solutions, creams, or bound to dressing materials. The silver ions bind to proteins and enzymes, damaging those systems, and to In debrided wounds, a 0. 5% silver nitrate (Ag. NO 3) solution is a potent disinfectant DNA, resulting in an antimicrobial effect via a heavy metal oxidative pathway , It does not injure regenerating epithelium in the wound and is bacteriostatic against S. aureus, E. coli, and P. aeruginosa

• Ag. NO 3 has limited wound penetration because the silver binds rapidly to the surface proteins. • Its hypotonic nature can cause osmolar dilution, resulting in hyponatremia and hypochloremia, so serum electrolytes must be monitored. • Ag. NO 3 turns black when exposed to light or on contact with tissues or chlorine-containing compounds, but this is nontoxic

SILVER SULFADIAZINE • Silver sulfadiazine (Silvadene, Thermazine, Flamazine, SSD), a 1% watersoluble cream, is a combination of sulfadiazine and silver with antimicrobial efficacy lasting up to 24 hours. While most effective against P. aeruginosa and the enterics, silver sulfadiazine has great utility against some yeasts, such as C. albicans. However, recent reports of P. aeruginosa resistance and inadequacy against some strains of Klebsiella have emerged.

SILVER SULFADIAZINE • More frequent dressing changes are required if a creamy exudate develops. Although this topical agent is facile in use and reduces pain, it retards wound healing • Unlike mafenide acetate, tissue-penetration of silver sulfadiazine is limited to the surface epidermal layer, and it is not associated with acid– base disturbances or pulmonary fluid overload

SILVER SULFADIAZINE • It can be used separately or in combination with other antibacterials. • An adverse drug reaction may be a reversible granulocyte reduction due to silver toxicity, although this is controversial and transient • Over multiple applications a pseudoeschar of silver sulfadiazine cream builds up on the wound, making assessment of the wound depth difficult because it then bears a strong resemblance to burn eschar

SILVER SULFADIAZINE • silver-containing dressings formulated to remain in place over a prolonged period. • On superficial burns, these dressings are utilized as functional skin substitutes to permit re-epithelialization in a bacterially suppressed, moist environment

SILVER SULFADIAZINE • The antimicrobial actions of the dressings derive from the silver ions, so their spectrum is thus defined. Each product’s dressing substrate and particular silver formulation provide different dressing characteristics; however, the release and efficacy of silver against bacteria in wounds have not been largely studied or reported

• no dressing, no matter how well marketed, replaces the tenets of burn surgery: aggressive débridement of devitalized tissue, coverage of wounds with skin, assiduous wound cleansing to remove pathogens and contaminants, and physical examination.

• Bismuth is another heavy metal commonly employed as a topical antimicrobial. It is bacteriostatic against enterics, but not cytotoxic to dermal fibroblasts and does not inhibit wound healing • It is usually used on the commercially available dressing Xeroform, a gauze impregnated with bismuth tribromophenate and petroleum jelly • Bismuth is also delivered in conjunction with iodine in the compounded paste, BIPP (1 part bis • muth subnitrate, 1 part liquid paraffin, and 2 parts iodoform)

ANTIBIOTIC-BASED TOPICAL ANTIMICROBIALS • Antibiotic-based topical antimicrobials define the fourth major class, and their mechanism of action is determined by the specific biochemistry characteristic of each particular agent. • Mafenide acetate (Sulfamylon), available both as an 8. 5% water-soluble cream and a 5% aqueous solution, is among the most commonly employed topical agents. While broad-spectrum, mafenide is particularly effective against all strains of Pseudomonas and Clostridium. The cream is applied twice a day and has the advantage that it does not require a dressing to adhere to wounds

ANTIBIOTIC-BASED TOPICAL ANTIMICROBIALS • Mafenide has excellent tissue penetration, including eschar. This penetration makes it the topical agent of choice for deep ear burns because it effectively prevents invasive chondritis. It can cause pain on application and, like other sulfa drugs, can lead to allergic reactions Since mafenide can inhibit carbonic anhydrase, metabolic acidosis can develop. Furthermore protracted use may lead to the growth of C. albicans

MAFENIDE ACETATE • While it can be used with other antimicrobials, mafenide acetate retards wound healing and reduces the breaking strength of healed wounds

• Gentamicin sulfate (Gentamicin) is an aminoglycoside available as a 0. 1% water-soluble cream or solution. It has broad-spectrum bactericidal activity against aerobes and is often deployed against P. aeruginosa. However, resistance can develop and sensitivities should be monitored • .

• Bacitracin/polymyxin (Polysporin) ointment is commonly used to prevent mechanical shear and suppress bacterial growth on newly grafted tissue. • Both drugs are cell wall lytic agents, and polymyxin is a topical analogue of colistin, discussed in the systemic antimicrobial section. Drug concentrations available in the ointment do not treat infection • Effectiveness in contaminated or infected burns post excision can be enhanced by use in combination with other agents, such as silver nitrate or mafenide. Prolonged use is associated with hypersensitivity development

• Nitrofurazone (Furacin), available as an ointment, solution, or cream, has been proved effective in the treatment of methicillin-resistant staphylococci • Mupirocin (Bactroban, pseudomonic acid A) is an antibiotic derived from the Pseudomonas fluorescens capsule and inhibits isoleucyl t-RNA synthetase and thus bacterial protein synthesis. 61 It is the topical treatment of choice for MRSA infections, gram-positive microbes, and intranasal carriage

• Mupirocin inhibits wound healing by a half-life of 2 days compared to controls, but the breaking strength of the wound is significantly enhanced. Due to rapid development of resistance, • mupirocin should not be used for longer than 10 days.

• Nystatin (Mycostatin, Nilstat) is an antifungal antibiotic produced by Streptomyces noursei. Nystatin is the highly potent topical equivalent of Amphotericin-B; both exert antifungal activity by binding to ergosterol and lysing fungal cell membranes. Low-dose applications of 100, 000 u/g as creams, lotions, or ointments are used as prophylaxis against fungal growth. • Liquid nystatin ‘swish and swallow’ is used prophylactically to prevent the oral or perineal overgrowth of yeast and fungi in patients receiving multiple systemic antibiotics