Topical therapy.
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Those factors that have contributed most to the control of burn wound sepsis in the burn patient since 1930 have been the advent of penicillin, the institution of burn center care, the availability of aminoglycosides and antifungal agents, the advent of topical therapy, the aggressive treatment of the burn wound by excisional therapy, a better understanding of respiratory therapy, the support of immune competence, and the recognition of the importance of nutritional support (Fig. 1). At the Shriners Cincinnati Unit, the extent of burn associated with a survival rate of 50 per cent has risen from 70 per cent in 1970 to 80 per cent in 1978. The better chance of survival for burn patients during this period can be directly related to a progressive improvement in the local and systemic measures available for the control of infection.
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Large TBSA burns have a deficiency of skin graft donor sites necessitating meshed skin autografts, cultured epithelial autografts or biosynthetic skin substitutes. Because these do not effect immediate complete biological closure of the wound, the burn victim remains at risk for life-threatening infection. Topical antimicrobials can protect colonization of these grafts from becoming invasive sepsis. However, many of these agents are cytotoxic to new partially keratinized epithelial cells. This study using a model of epithelialization kinetics of human meshed skin grafts explanted to athymic 'nude' rats evaluated: (1) the effect of bacterial colonization on the rate of closure of meshed graft interstices; (2) the efficacy of 5% Sulfamylon solution for bacterial control and (3) the effect on interstitial closure rates caused by control of bacterial proliferation. Results showed the rate of interstitial closure was progressive over 7 days in noncontaminated grafts treated with moistened saline dressings. Areas of total closure of a 1:1.5 meshed graft were seen as early as 5 days. When grafts were inoculated with 10(2) or 10(3) Pseudomonas aeruginosa organisms and treated with saline moistened dressings, the resultant bacterial load rose to 10(6) organisms, less than 3% of the interstices closed and grafts were destroyed. With the same organism level of contamination, bacterial levels were eradicated with topical 5% Sulfamylon solution, interstitial closure rates returned to normal and areas of total meshed graft closure were seen by day 4. These data demonstrate the efficacy of 5% Sulfamylon solution on epithelialization kinetics of contaminated meshed skin grafts.
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The extensively burned or severely injured patient is at increased risk of wound infection as well as of infection of other organs as a result of various degrees of impairment of host defense mechanisms. The incidence of burn wound and other infections increases as the severity of injury increases. The ease with which gram-negative, opportunistic organisms, especially Pseudomonas aeruginosa of either endogenous or exogenous origin, can colonize and invade the immunosuppressed patient demands an active infection-surveillance program. Topical therapy for burn wounds with any of three available agents has significantly reduced the occurrence of invasive pseudomonas burn-wound sepsis, but none of the agents sterilize the burn wound, and the microbial flora of the burns of any given patient may escape from control and invade viable tissue. Clinical identification and biopsy confirmation of invasive burn-wound sepsis necessitates changes in both wound and general care, with surgical and antibiotic treatment guided by the extent and depth of wound invasion. Immunologic prophylaxis and treatment of pseudomonas infections, although attractive, remain of unverified clinical effectiveness. Effective treatment of pseudomonas septicemia secondary to invasive burn-wound sepsis and of pseudomonas infections in other organs is dependent on early diagnosis, appropriate antibiotic therapy guided by sensitivity testing, and adequate surgical intervention when required.
Oxygen consumption (VO2) and colonic temperature (Tc) were measured in groups of rats before and after 30% total body surface, full thickness burns. Some wounds were seeded with Pseudomonas aeruginosa or Staphylococcus epidermidis, and some seeded wounds were treated with Sulfamylon or Silvadene. Three groups became bacteremic (B) during the 2-3 week period of observation. At an ambient temperature (Ta) of 32 C, VO2 of the B group rose from 0.83 +/- 0.01 to 1.20 +/- 0.01 ml/hr/g (mean +/- S.E., p less than 0.001) versus 0.81 +/- 0.01 to 0.99 +/- 0.02 for nine nonbacteremic (NB) groups (p less than 0.001). Tc increased only in the B groups--from 36.8 +/- 0.1 to 37.7 +/- 0.1 C (p less than 0.001). In the second or third week postinjury, VO2 of the NB rats was reduced when Ta was increased to 34 C; Tc followed changes in Ta. Sulfamylon lowered VO2 of P. aeruginosa seeded, NB rats. The metabolic cost of wound contamination appeared to vary with bacterial strain. The metabolic effects of infection appear to be a continuum, beginning with a modest rise in VO2 and progressing to greater increases in VO2 and Tc with wound invasion and systemic infection.
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We present a new laboratory method to test the sensibility of clinically isolated strains to topical agents. It is a method of dilution of the whole cream in a solid medium. The cream is weighted, suspended in sterile water, and maintained at 45 degrees C. Then a volume of that suspension is added to the agar, maintained at 45 degrees C also. The mixture is agitated and plated. Afterwards 25 strains are inoculated by a Multinoculator (Cetin, Bs. As., Argentina). After incubation (18 hours at 37 degrees C), the results are obtained by observing the presence or absence of bacterial development. The minimal inhibitory concentration is calculated as the lowest concentration that inhibited growth. It is a simple, economical, and reproducible method.
Pilot in vitro studies demonstrated that nystatin combined with Silvadene (silver sulfadiazine 1% [Marion Laboratories, Inc., Kansas City Mo.]) or Furacin in a 1:1 ratio was equally effective against Candida albicans and ATCC strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, but Sulfamylon (Winthrop Pharmaceuticals, Winthrop, N.Y.) combined with nystatin demonstrated an antagonistic response. Therefore we examined the susceptibility to nystatin of 165 clinical isolates, both gram-positive and gram-negative, to nystatin combined with Silvadene or Sulfamylon and 144 isolates to nystatin and Furacin. Both Silvadene and Furacin combined with nystatin were equally effective against the microorganisms as were the individual drugs. Conversely, Sulfamylon combined with nystatin lost its antimicrobial capability (93.3% resistance, p less than 0.001). On the basis of the in vitro results, 93 patients with acute burns were treated with the appropriate topical antimicrobials from April 1988 to September 1988. Of the 93 patients treated, 90 had neither a major systemic bacterial nor a Candida sepsis, and none of these patients had associated localized burn wound sepsis during their hospital stays. These 90 patients were discharged without any documented signs of infection. The average burnsize was greater than or equal to 29.44% total body surface area. These data suggest that the antimicrobial properties of nystatin, when combined with Silvadene and Furacin, remain effective. Consequently, such combinations have been effective in controlling both local and systemic Candida and bacterial burn wound sepsis.
Severely burned patients experience a bone lesion consisting of markedly reduced bone formation and evidence of decreased resportion. The cause of the lesion may be multifactorial, but aluminum loading, which also occurs in patients with burns, has been documented to produce this type of injury in both humans and animals. To assess the risk of aluminum loading with patients with burns, we analyzed fluids, creams, and medication used in the management of acute burn injury for aluminum content. These substances were classified according to route of administration: cutaneous, enteral, or parenteral, to assess the risk of aluminum loading. Cutaneous exposure to aluminum is greatest from baths, which may provide up to 8 mg aluminum. However, the dynamics of aluminum entry into the blood via a damaged skin barrier are unclear. Enteral exposure to aluminum is no greater than daily dietary exposure. Parenteral sources of aluminum, especially 25% human serum albumin and calcium gluconate, provide the most significant risk of loading because of direct introduction of aluminum into the circulation. Substitution with a different brand of albumin and calcium chloride can reduce the parenteral aluminum load by as much as 95% and minimize any role aluminum may play in the pathogenesis of this bone lesion.
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Seven burn patients treated with silver nitrate dressings were studied during the first 10 days after injury. Minute ventilation, oxygen consumption, and ventilatory equivalent were measured. Minute ventilation was increased two- to threefold, as was oxygen consumption. Ventilatory equivalent was only slightly increased. THree patients were initially treated with silver nitrate, and then, when clinically stable, were switched to Sulfamylon. They showed a 50% rise in ventilation, tidal volume, ventilatory equivalent, and a slight increase in respiratory rate and VD/VT. In addition, their PO2 increased and base excess fell. Five normal subjects were then given Diamox, and their minute ventilation, O2 consumption, and ventilatory equivalent were measured at rest, with a standard exercise, and with an added dead space. Diamox produced only a 25% increase in minute ventilation and ventilatory equivalent. The results suggest that, although some of the increased ventilation of Sulfamylon is due to carbonic anhydrase inhibition, another factor, such as pain casued by the topical agent, also plays a role.
This study evaluated the cytotoxicity of commonly used topical agents to human dermal fibroblasts and epidermal keratinocytes, which play a prominent role in wound healing. The effects of these topical agents were assessed using two separate assays for the fibroblasts--tritiated thymidine incorporation and the uptake of a vital dye (neutral red). Keratinocytes were evaluated with the neutral red assay. Serial dilutions of each of 10 commonly used topical agents produced decreases in both the uptake of neutral red and the incorporation of thymidine at clinically relevant doses. Only Neosporin G.U. irrigant showed no significant difference compared with controls in the assays for both the fibroblasts and the keratinocytes. Careful attention must be paid to which agent is used in the clinical setting, since many of these can have profound effects on cells that influence wound healing.
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A case of atopic reaction to Sulfamylon is described that occurred in a patient receiving this medication as a topical treatment for burned ears. The presenting signs were similar to those of a persistent chondritis, with which it was initially confused. All signs and symptoms cleared rapidly after the Sulfamylon was discontinued. Physicians should be aware of this entity so as to avoid inappropriate surgical debridement of ears with this relatively minor problem.
The use of cultured human keratinocytes in an in vitro comparison of topical antibacterial toxicity for epithelial cells was examined. The complement of three assessments allows testing of epithelial migration, growth, and survival. The three assessments included (1) flow cytometry for determination of cell survival, (2) a comparison of confluent cell culture growth after antibacterial exposures, and (3) an evaluation of cell migration using a technique of dermal explants to study radial migration. A comparative ranking of the toxicities of the various topical antibacterials was determined with the three assessments. This has confirmed anecdotal reports that many of the topical antibacterials are cell-toxic and may inhibit wound healing. This information can be directly extrapolated to the clinical setting, unlike many of the animal data for wound healing that currently exist.
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