Topical therapy for control of bacteria in the burn wound

Abstract

The concept of burn wound sepsis and the demonstration of the avascular nature of the burn wound paved the way for the development of effective antibacterial therapy of the burn wound. Many agents have been tried, but the most effective are those with a broad spectrum of antibacterial activity, lack of developing resistance, low toxicity, and active penetration of the wound. The resultant lowering of mortality and improvement in patient care have dramatically altered the prognosis of burn injury. The primary drugs in use today, their advantages and limitations, and the pathophysiology of the burn wound and burn wound sepsis are presented.

Activity of topical antimicrobial agents against multidrug-resistant bacteria recovered from burn patients

“…This has been described in prior studies. While it is concerning that mafenide acetate does not perform well in vitro, there have been multiple studies in vivo documenting its ability to diffuse through eschar so one might interpret the large zones of inhibition as more indicative of mafenide's performance in vivo [3,5,23,33]. It is not surprising that zones of inhibition are scant for bacitracin, as it has been shown previously to not diffuse well through agar [23].…”

“…Inhibits nucleotide synthesis [8] Bacteriostatic against gramnegative organisms including P. aeruginosa and gram-positive organisms [13,39] 11.1% cream, 5% solution Rapidly penetrates full thickness eschar making it effective in heavily colonized wounds and established burn wound infection [3,5,33] 11.1% concentration is painful when applied to the superficial partial-thickness burns with intact free nerve endings [3,40] Can dry into a tenacious gum (neoeschar) that attaches to the wound requiring hydrotherapy to remove [41] 5% aqueous solution is less painful and does not leave a residue [42] Absorbed systemically with highest blood levels of mafenide and its metabolite (pcarboxybenzenesulfonamide) in 2nd-4th hour resulting in urinary alkalinization from carbonic anhydrase inhibition [43] Possible metabolic acidosis, especially in patients with pulmonary dysfunction such as atelectasis or pneumonia that limits respiratory compensation [14,40,44] Electrolyte disturbances [45] 7% incidence of hypersensitivity, usually a rash [5] Rapid absorption from the tissue requires twice daily application to keep levels high enough for bacterial inhibition [33] No resistance reported to P. aeruginosa [6] Some resistance described to Providencia [5] Mortality benefit in prevention of burn wound sepsis described in animal models [13] Reduction in mortality and the rate of invasive burn wound infections in patients from before the introduction of mafenide to after, particularly in patients with 40-79% TBSA in one study [5] and between 20 and 59% TBSA in another study [14,15] Found to be the most effective topical agent against A. baumannii [18] Poor correlation between broth microdilution and agar well diffusion [23] b u r n s 3 6 ( 2 0 1 0 ) 1 1 7 2 -1 1 8 4…”

“…Reduces nutritional and metabolic losses by decreasing evaporative water loss [3,33,54] Painless on application [33] Poor eschar penetration [3] so can be used for prophylaxis but not treatment of burn wound infections [55] Turns black upon contact with tissues and can stain linens [53,54,56,57] Electrolyte disturbances due to leeching of cations across the wound into the hypotonic solution, ''sodium sink'' [3,6,20,33,40,54] Aerobacter cloacae and some other gram-negative bacteria can convert the nitrate to nitrite causing methemoglobinemia [3] Problems with tissue irritation and delayed wound healing have been reported [3,57] Acquired resistance is uncommon [33,58] Resistance is often unstable and isolates can revert back to sensitive [59] Has been used in burn treatment since at least the 18th century, initially in a hardened form called lunar caustic [10] Reduced mortality in burned mice with P. aeruginosa infection by 30% [16] Application to >40% TBSA wounds delayed sepsis and reduced mortality from 81% to 33% [54] b u r n s 3 6 ( 2 0 1 0 ) 1 1 7 2 -1 1 8 4 Interferes with electron transport and nucleotide synthesis [8] Binds to bacterial cell membranes and cell wall, penetrates the cell, and denatures bacterial DNA and RNA resulting in inhibition of replication [9,17] Bactericidal to gram-negative and gram-positive organisms including Pseudomonas spp. and S. aureus (MRSA) [3,20] Some activity against Candida spp.…”

“…and herpesviruses at high concentrations [9] Combination of the silver ion and sulfadiazine in a 1% water soluble cream introduced in 1968 [3] Painless on application [60] Accelerated deep dermal wound healing and reduced conversion rate of deep dermal wounds to full-thickness skin wounds [17] Delayed eschar separation [17] Poor eschar penetration Reversible granulocyte depression especially in >30% TBSA burns [3,6,9]. This occurs early in therapy (postburn day 2) and mainly affects mature neutrophils though has not been shown to increase risk of infectious complications [61] Not very effective in established infection due to minimal eschar penetration [49] Appears as a thick creamy exudates on the wound, which can be confused with pus [3,53] Rare hypersensitivity reactions to sulfa moiety reported [33,62] and rare hemolysis in setting of G6PD deficiency [21] Systemic absorption especially in more vascular partialthickness burns [21,63] though an experimental model using radioactive silver sulfadiazine showed silver only in the skin and not in the blood/organs [53] Rare argyrosis [63] if silver levels are many times normal [21] Resistant to most Enterobacter cloacae and some Pseudomonas spp. [5] Plasmid-mediated resistance against some gram-negatives including A. baumannii and P. aeruginosa has been reported in burn patients [9,18,21] Reduced mortality in burned mice with P. aeruginosa infection by 60-75% [16] Poor correlation between broth microdilution and agar well diffusion [23] Triple antibiotic ointment (Neomycin, Polymyxin B, bacitracin)…”