Evaluation of the penetration strength, bactericidal efficacy and spectrum of action of several antimicrobial creams against isolated microorganisms in a burn centre.

The antibacterial activity of eight antiseptic creams: 1 per cent silver sulphadiazine; 0.2 per cent nitrofurazone; 0.1, 0.5 and 1 per cent chlorhexidine; 2.2 per cent cerium nitrate; 10 per cent povidone iodine; and 1 per cent silver sulphadiazine with 2.2 per cent cerium nitrate were evaluated in vitro. The evaluation included the minimum inhibitory concentration (MIC) against 100 microorganisms isolated from burn patients, the chronology of the bacterial activity against Ps. aeruginosa and Staph. aureus and the penetration strength of the creams through a novel in vitro model contaminated with 17 microorganisms of different species isolated from burn patients. The results revealed that 0.5 per cent or 1 per cent chlorhexidine, 2.2 per cent cerium nitrate, and 1 per cent silver sulphadiazine with 2.2 per cent cerium nitrate were the creams which were effective at the highest dilutions. 0.5 per cent chlorhexidine and 10 per cent povidone iodine had the greater bactericidal activity. Finally, 0.2 per cent nitrofurazone showed greater penetration strength within the eschar model in comparison with the weaker penetration of 0.5 per cent and 1 per cent chlorhexidine and the absence of penetration by the rest of the antibacterial creams.     

Bacteriological effect of cerium-flamazine cream in major burns

A controlled trial of the use of either 0.05 per cent chlorhexidine for bathing burn wounds or the topical application of a cream containing cerium nitrate and silver sulphadiazine showed that the cerium-flamazine cream significantly reduced the degree of Pseudomonas aeruginosa contamination of the burn wounds of patients with burns covering more than 15 per cent of the body surface area. The adherent eschar produced by treatment with cerium-flamazine provided a satisfactory wound cover until tangential excision could be carried out.     

Topical chemoprophylaxis: Trials in silver phosphate chlorhexidine,silver sulphadiazine and povidone iodine preparations

A controlled trial showed that 1 per cent silver sulphadiazine (SSu) cream applied daily (or at intervals of 2 or 3 days) to burns had greater prophylactic value against Pseudomonas aeruginosa than a cream containing 0.4 per cent silver phosphate with 0.2 per cent chlorhexidine gluconate (SPCI). In another controlled trial, SSu cream had greater prophylactic value against Staphylococcus aureus, P. aeruginosa, proteus species and miscellaneous coliform bacilli than a 10 per cent povidone iodine (PVP-I) cream. It was inferred, from the results of an earlier trial, that silver nitrate chlorhexidine (SNCI) cream would be more effective than SPCI cream as a prophylactic agent against P. aeruginosa, apparently because of the greater solubility of silver nitrate; for this reason, SNCI cream was judged to be an appropriate substitute for SSu cream when sulphonamide-resistant Gram-negative bacilli were predominant in the ward.A trial of 10 per cent povidone iodine and 0–5 per cent silver nitrate solutions applied 6 hourly to exposed bums of the face, compared with no topical application, showed that both solutions reduced bacterial colonization of the burns, but there was no significant reduction in colonization by individual pathogens.     

Use of topically applied silver sulphadiazine plus cerium nitrate in major burns

All patients hospitalized between May 1987 and June 1988 suffering from burns covering over 50 per cent of the body surface area were treated by topical application of a cream containing cerium nitrate (0.05 M) and silver sulphadiazine (0.03 M) (CN + SSD). Eleven patients were included in this series, with a mean age of 35 years (range 22-65), a mean total burn size of 78 per cent (range 50-96 per cent) and full skin thickness covering a mean of 48 per cent (range 10-91 per cent). Eight patients survived (73 per cent) (mean age 36 years; mean total burn surface 73 per cent; mean full skin thickness burn surface, 38 per cent). These results are far better than those obtained in our Unit where a survival rate of 34 per cent was obtained in a comparable series of patients treated before 1987. Sixty positive blood cultures were obtained, which included a large variety of organisms with a slight predominance of Staph. aureus, Candida albicans and Ps. aeruginosa. Wound cultures were positive in 72 per cent of swabs and showed a predominance of Ps. aeruginosa (59 per cent of all the strains isolated). Even if CN + SSD appears in this series not to be very efficient in preventing wound colonization and septic complications, it permitted a very high survival rate in the treated patients, taking into account the extreme severity of the injuries. This beneficial effect is probably the consequence of the protective action of the yellow-green eschar formed by CN + SSD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns

Effective topical antimicrobial agents decrease infection and mortality in burn patients. Chlorhexidine phosphanilate (CHP), a new broad-spectrum antimicrobial agent, has been evaluated as a topical burn wound dressing in cream form, but preliminary clinical trials reported that it was painful upon application. This study compared various concentrations of CHP to determine if a tolerable concentration could be identified with retention of antimicrobial efficacy. Twenty-nine burn patients, each with two similar burns which could be separately treated, were given pairs of treatments at successive 12-h intervals over a 3-day period. One burn site was treated with each of four different CHP concentrations, from 0.25 per cent to 2 per cent, their vehicle, and 1 per cent silver sulphadiazine (AgSD) cream, an antimicrobial agent frequently used for topical treatment of burn wounds. The other site was always treated with AgSD cream. There was a direct relationship between CHP concentration and patients' ratings of pain on an analogue scale. The 0.25 per cent CHP cream was closest to AgSD in pain tolerance; however, none of the treatments differed statistically from AgSD or from each other. In addition, ease of application of CHP creams was less satisfactory than that of AgSD. It was concluded that formulations at or below 0.5 per cent CHP may prove acceptable for wound care, but the vehicle system needs pharmaceutical improvement to render it more tolerable and easier to use.     

The use of a topical antibacterial agent (silver sulfadiazine) on soft-tissue wounds

Reducing the quantitative level of bacterial contamination in an open, acute or chronic, soft tissue wound below the critical level of 10(5) bacteria per gram of viable tissue is essential to delayed primary closure. First step in the management of the contaminated or infected wound is accurate local debridement, preferably with pulsating jet irrigation. Topical antibacterial agents, specifically silver sulfadiazine cream, are then usefully employed to reduce the bacterial count. Contrary to systemic antibiotics, these agents penetrate adequately into the open, granulating wound with a direct bacteriostatic or bactericidal action on a wide spectrum of gram positive and negative organisms, without the effect of local tissue injury typical of topical antiseptics. The use of topical antibacterials, traditionally confined to the treatment of the burn wound, the open "difficult" wound for excellence where control of local infection is first priority, provides a rapid local reduction of the bacterial level and paves the way to the final goal of primary delayed closure of the wound, either direct or with the use of grafts or local, distant, or free flaps.     

湿润烧伤膏抗感染作用的实验研究

我们采用大鼠２０％Ⅲ度烫伤创面接种绿脓杆菌ＡＴＣＣ－２７８５３作为实验治疗模型，旨在评价湿润烧伤膏外用治疗烧伤的防治感染功效。于接种绿脓杆菌后１０分钟、８小时、２４小时和４８小时开始外用湿润烧伤膏治疗，并以１％的Ａｇ－ＳＤ霜，１．２％的Ａｇ－ＦＬＸ霜和基础霜剂作为对照。治疗４８小时后送血培养，痂下细菌计数及组织病理学检查，以此作为评价指标。４种外用药物在体外对绿脓杆菌，大肠杆菌和金黄色葡萄球菌做抑菌试验，结果表明，Ａｇ－ＦＬＸ抗菌作用和疗效最强，Ａｇ－ＳＤ次之，而湿润烧伤膏的各项指标和基础霜剂间差异无显著意义（Ｐ＞０．０５）。说明湿润烧伤膏在防治烧伤感染方面几乎没有作用。     

Débridement of the burn wound with sutilains ointment

Twenty-one patients with fresh full-thickness burns received a course of two daily applications of sutilains ointment to an area of their burn wound not exceeding 9 per cent of the body surface. Twelve had a mirror-image control burn site of equivalent depth and extent, which was treated identically except sutilains applications were omitted. Good débridement, defined as a wound free of adherent eschar, was observed in 9 patients (43 per cent). The remaining patients' wounds had adherent eschar at the end of the test, or demonstrated equal débridement of both the test and control site. Good débridement was not promoted by increasing the frequency of wet dressings between sutilains applications. Débridement was better in patients receiving more than 8 days of applications. A higher percentage of patients receiving silver sulphadiazine demonstrated good débridement than those receiving gentamicin or no topical antibacterial agent. Burn wound bacterial colonization pattern in sutilainstreated patients did not vary from that observed in those patients receiving only topical antibacterial agents alone.Histological examination revealed that areas with good débridement showed an intense inflammatory cell response and dissolution of the elastic fibres. Control sites and areas with poor débridement showed a lesser inflammatory response and preservation of elastic fibres. No explanation for the variable response to sutilains was apparent histologically. Because of pain associated with application, cost and the unpredictability, sutilains should not be used indiscriminately without monitoring its response carefully and should be used only in conjunction with a topical antibacterial.     

Burn wound biopsy bacterial quantitation: a statistical analysis.

Sequential paired punch biopsy samples were taken from three separate locations on each of four burn patients and were quantitated for the number of viable bacteria per gram of tissue. The range (log10 0.02 to log10 1.51) and the standard deviation (log10 0.67) were determined for each pair. The 95 per cent confidence interval based on any single observation, x, was determined to be x +/- 1.31. It is concluded that the burn wound biopsy is a reliable procedure for quantitating organisms in a burn wound and that changes in sequential samples give an indication of the dynamics of infection in the burn patients.     

Cerium nitrate/silver sulphadiazine: synergism or antagonism as determined by minimum inhibitory concentration

The topical antimicrobial effects of silver sulphadiazine in burn wound therapy are well documented. Clinical studies have recommended the use of cerium nitrate/silver sulphadiazine cream, which apparently decreases mortality rates from burn wound sepsis due to Gram-negative organisms. In vitro assays of minimum inhibitory concentration (MIC) by agar diffusion assay demonstrates that Pseudomonas aeruginosa is more resistant to cerium nitrate (100 per cent at 100 μg) and cerium/silver combination (40 per cent at 100 μg) than to silver sulphadiazine alone (19 per cent at 100 μg). This resistance was further demonstrated at concentrations from 50 to 200 μg. The effect of cerium nitrate upon silver sulphadiazine in combination is apparently one of antagonism rather than synergism.     

Evaluation of topical therapy with silver-kaolin (Argostop) in an experimental model of burn wound sepsis

Burn wound therapy with silver-kaolin, a topical agent applied as an aerosol spray, was evaluated in male rats given a 20 per cent total body surface area, full thickness dorsal scald burn. Burn wounds treated with silver-kaolin healed at rates comparable to untreated wounds. No significant differences were noted in the numbers or types of organisms colonizing the wounds of treated and untreated rats at 5, 12 and 19 days post-burn. To evaluate the effectiveness of silver-kaolin in treating burn wound sepsis, rats were inoculated on the wound surface with 2.5 x 10(8) Pseudomonas aeruginosa. This inoculum resulted in 100 per cent mortality in untreated rats. Rats treated with silver-kaolin had a mortality rate of 71 per cent, compared to a 9 per cent mortality rate in rats treated with 1 per cent silver sulphadiazine. When silver-kaolin was applied to the wound prior to bacterial inoculation, the mortality rate was reduced to 6 per cent. When wounds were treated with kaolin alone and then inoculated with bacteria, the mortality rate was 50 per cent, indicating that part of the effectiveness of silver-kaolin appeared to be due to a barrier effect. These results indicate that silver-kaolin may be useful for preventive topical antimicrobial therapy of acute burns or after wound debridement or excision, but is not suitable for therapy of wounds previously colonized by microorganisms.     

The effect of some ointment bases on the systemic absorption of tobramycin from various wound surfaces of burned patients

Three kinds of 0·2 per cent tobramycin ointment were prepared with tobramycin and 3 ointment bases (cream, polyethylene glycol and hydrophilic petrolatum), and applied to the various wound surfaces of 5 burned patients. The systemic absorptions of tobramycin were compared with the values of the tentative AUC (area under the curve of tobramycin blood level, μg.h/ml.g) until 12 hours after the applications, by determining tobramycin level in blood. Similar values of AUC from the cream and polyethylene glycol ointments were obtained, while that of hydrophilic petrolatum ointment was very low. The systemic absorption of tobramycin from the polyethylene glycol ointment was studied when the ointment was applied to the wound surfaces of 7 patients with partial-thickness bum, 9 patients with full-thickness burn and 6 patients with burn ulcer. The mean values of the tentative AUC of patients with partial-thickness burn, full-thickness burn and burn ulcer were found to be 0·06, 0·03 and 0·15, respectively. These results showed that cream and polyethylene glycol bases should be used carefully as a vehicle of tobramycin ointments because of the rapid systemic absorption of tobramycin from human burn wounds, especially burn ulcer.     

Blood glucose level as an aid in the diagnosis of septicaemia

Although burn wound sepsis is primarily managed with topical antibacterials and excision-débridement of necrotic tissue, true septicaemia with bloodstream invasion requires systemic antibiotics. Multiple and broad spectrum antibiotics have been associated with fungal infection and emergence of resistant organisms in the burned patient. Therefore, it is beneficial to use a specific bactericidal drug whenever possible.In a series of 214 patients with septicaemia, the mean glucose level in patients with Gram-positive organisms was 165 mg per cent compared to 101 mg per cent for patients with Gram-negative organisms. In non-diabetic patients, the difference was also marked-138 mg per cent in the Gram-positive septicaemias and 97·5 mg per cent in the Gram-negative septicaemias. Of all the patients with septicaemia having a blood glucose of <110 mg per cent, over 80 per cent showed Gram-negative organisms in their blood cultures. Of all those whose blood glucose concentration was > 130 mg per cent, over 80 per cent showed Gram-positive organisms in the cultures.For the past three years, blood glucose levels have been drawn each time the patient's temperature is greater than 38·5 °C (101·3 °F) at the time blood cultures were drawn. This has allowed the burn team to gain additional information prior to culture results. Using these guidelines, the blood glucose level has predicted the type of organism in 4 out of 5 of cases of septicaemia. Therefore, if the diagnosis of septicaemia is made and antibiotics are felt indicated, a Gram-negative bactericidal antimicrobial is administered if the glucose is < 110 mg per cent until blood culture results are available. If the glucose is > 130 mg per cent, a Gram-positive bactericidal antimicrobial agent is instituted. This has allowed us to decrease the number of antibiotics used and to decrease the spectrum of antimicrobials in our facility.     

Rapid quantification of bacterial and fungal growth in burn wounds: biopsy homogenate Gram stain versus microbial culture results

A prospective analysis of 370 burn wound biopsies was done to correlate Gram-stain results from biopsy homogenates with quantitative culture results. The number of bacteria seen in a total of 10 oil immersion microscope fields of Gram-stained homogenates was correlated with significant microbial growth (1 x 10(5) organisms/gram of tissue) of the same biopsy homogenate plated on trypticase soy agar. Of the biopsies examined, Gram-negative rods were present in 36.8 per cent, Gram-positive cocci in 49.7 per cent and yeast in 15.9 per cent. Mixtures of organisms were present in 24.3 per cent. When Gram stains showed one or more organisms per oil immersion microscope field, the correlation with significant microbial growth was 94.5 per cent or more. When five or more organisms were seen per field, the correlation with significant growth became 97 per cent or greater. When no organism was seen on Gram stain, the cultures grew significant numbers of organisms 19.1 per cent of the time or less. This false-negative rate was considered to be high. It is believed, however, that this method of early detection of significant burn wound microbial growth may prove to be valuable in the management of severely burned patients.     

Permeability of thermally damaged skin V: Permeability over the course of maturation of a deep partial-thickness wound

The permeability of eschar is an important factor governing rational approaches to topical control of burn wound sepsis. Previous work has shown the burn wound to have a highly variable permeability immediately after burning depending on the manner of burning. But the burn is also a dynamic wound and its physical state changes during the process of maturation. The present studies are an early attempt to characterize wound permeability as a function of maturation. Hairless mice were burned dorsally for 15 seconds on a metal surface maintained at 80°C. The time and temperature conditions were chosen to effect a deep partial-thickness to full-thickness injury on the animal. Mice were sacrificed daily post burn over a 2-week period and the permeabilities of ³H-methanol and ¹⁴C-butanol through the excised eschar were measured. The eschar permeability coefficients were directly compared to permeability coefficients for the same compounds found with abdominal skin sections taken concurrently from each animal. It was observed that the branding initially caused a 50 per cent increase in the permeability of methanol and a 300–400 per cent increase in the permeability of butanol. These factors held over the first 4 to 5 days of maturation. Thereafter permeabilities tended to increase, gradually at first, but accelerating to a maximum which was observed at approximately 10 days. At the maximum, methanol's permeability was 20 times and butanol's 12 times their normal values. For both compounds permeability of eschar decreased past the maximum until termination of the studies at 14 days.     

A liposome hydrogel with polyvinyl-pyrrolidone iodine in the local treatment of partial-thickness burn wounds

Local treatment of burn injuries with conventional anti-infective preparations does not provide the moist environment that promotes fast wound healing. In a randomized controlled trial the effects of liposome polyvinyl-pyrrolidone-iodine (PVP-I) hydrogel, a novel formulation of PVP-I in a liposome hydrogel with high water-binding capacity, were investigated in 43 patients with partial-thickness burn wounds in an intraindividual comparison with a conventional silver-sulfadiazine cream. Treatment with liposome PVP-I hydrogel resulted in significantly faster complete healing of the burn wounds compared with silver-sulfadiazine cream (9.9 +/- 4.5 days versus 11.3 +/- 4.9; P < 0.015). The cosmetic result (smoothness, elasticity, appearance) was rated as excellent for 37.0% of study wounds with liposome PVP-I hydrogel compared with 13.0% of wounds treated with silver-sulfadiazine cream. Local tolerability was good; handling and change of dressing were rated as easy. Local treatment with liposome PVP-I hydrogel thus provides fast wound healing with a favorable cosmetic result.     

Studies on systemic absorption of tobramycin in polyethylene glycol ointment applied to wounds of burn patients

The penetration of tobramycin ointment (0.2 per cent) through human burn wounds was studied in two patients with superficial dermal burn (SDB) and deep dermal burn (DDB), two patients with DDB, one patient with full thickness burn (FB) and one patient with burn ulcer (BU). After application of the ointment, the absorption of tobramycin occurred promptly with a peak level at 2-6 h in the sera of patients with SDB + DDB and DDB only. In the BU patient it was found at 2 h; while in the FB, at 10-12 h. The excretion of tobramycin into the urine was also studied. The absorption rate constants (ka) of the two SDB + DDB patients were 0.31 and 0.74, of the two DDB patients, 0.079 and 0.18, and those of the DB and the BU patients, 0.053 and 0.95, respectively. The absorption ratios of tobramycin (amount excreted into the urine during 24 h/applied dose) were different, depending on the condition of the burn wound, and ranged from a low of 10.3 per cent (FB) to a high of 44.0 per cent (BU). These results show that the treatment of burn patients with tobramycin ointment to control burn wound infection should be carefully supervised, especially in the case of BU.     

银锌霜在大面积烧伤中的应用

目的总结１９９１年１月至１９９５年１１月银锌霜在４８例ＴＢＳＡ大于３０％的烧伤病人创面的应用。方法将同期应用碘络醚的３５例病人作为对照，两组病人的平均年龄、烧伤面积、Ⅲ度面积无显著差别，用药方式均以半暴露为主。结果银锌霜组能显著增加细菌转阴率，减少抗生素应用时间及植皮手术次数，缩短愈合时间。结论银锌霜具有较强的抗感染能力，是大面积烧伤病人的良好外用药。     

A comparative study of the in vitro permeation characteristic of sulphadiazine across synthetic membranes and eschar tissue

Infections of burn wounds are the source of significant problems in burn patients. Early excision of eschar tissue is an ideal solution to avoid sepsis. When early excision is not feasible, the application of topical antimicrobial formulations may be used to control burn wound sepsis. An understanding of the barrier properties of eschar tissue is essential for optimal design of topical antimicrobial formulations. To date, little research has been conducted on the permeability of eschar. Silver sulphadiazine (SSD) is the most frequently used topical agent in burn management. In this study, the permeation of sulphadiazine from aqueous saturated solutions of SSD through human full‐thickness burn eschar tissue was studied and compared with permeability through silicone and Carbosil as model membranes. The permeation of sulphadiazine through eschar tissue was significantly higher than that through silicone and Carbosil membranes (P < 0·05). Deconvolution of the data showed that the apparent sulphadiazine diffusion coefficient was much higher in eschar tissue and was comparable to transport through an aqueous protein gel. Further studies on a greater number of compounds are suggested to elucidate the utility of such membranes as predictive models of drug permeability through eschar tissue.     

Assessment of topical therapy of the burn wound with silver sulphadiazine after its use for 15 years in a burn unit

A comparative study of patients receiving or not receiving topical applications of 1 per cent silver sulphadiazine cream as treatment for burn wounds has shown that the drug is still effective in significantly reducing the amount of bacterial contamination of burn wounds, even after 15 years of use in our Burn Unit. Consequently the overall mortality due to burn wound sepsis has been decreased in this Burn Unit.