Annals of Burns and Fire Disasters - vol. X - n. 2 - June 1997

FLAMAZINE CREAM IN BURNS

Hadjiíski 0., Lesseva M., Tzolova N.

Centre for Burns and Plastic Surgery, Pirogov Medical Institute, Sofia, Bulgaria


SUMMARY. Silver sulphadiazine, used for the first time by Fox in 1968, is now the drug of choice for local treatment of burn wounds, and Flamazine, its most popular compound, meets most of the criteria for the ideal local agent. The aim of this study was to establish the efficacy of Flamazine in the prevention of bacterial infection and in burn treatment. The study concerned 50 hospitalized patients of either sex, aged between 1 and 76 years, with second- and third-degree burns in 5 to 70% T13SA. The bacteriological results of Flamazine application in 35 patients are presented. Both the open and the closed methods were used for Flamazine application. All the patients were treafed successfully. In deep burns the eschars were soft, slightly moist, metal grey in colour, and with no inflammation area in or around them or any bacterial growth, this making it possible to perform early surgical necrectomy. A good process of epithclialization initiated after debridement of superficial burns. In 27 patients (77.0%) the wounds remained without bacterial growth from the time of the patients' admission until they were operated on or until epithelialization. The bacteriological results were evaluated as very good in 31 cases (88.5%) and good in four (11.5%), with no unsatisfactory result. It is concluded that local treatment with Flamazine is very important for the favourable course and outcome of the burn disease as it prepares deep burns for early operative treatment and promotes rapid epithelialization of superficial burns.

Introduction

Burn wound infection is the main source of bacteraemia and an important cause of graft failure, which determines the essential role of the agents for local antibacterial trteatment. 1,2 Unlike systemic antibiotics, local agents penetrate burn wound surfaces with direct bacteriostatic and bactericidal action, without damaging the tissues .2,3 Silver sulphadiazine, used for the first time by Fox in 1968, is now the drug of choice for the local treatment of burn wounds.
Flammazine consists of 10 mg per gram micronized silver sulphadiazine in a hydrophilic cream base. This concentration provides delivery of the agent in quantities above those necessary for in vitro inhibition of the growth of susceptible micro-organisms. Silver sulphadiazine is highly effective in vitro against gram-positive and gramnegative bacteria and fungi, including the common pathogens found in burns (Table 1).

Bacterial species

Staphylococcus aureus
Coagulase-negative staphylococci
Streptococcus heta-haeniolyticus
Enterococcus
Pseudomonas aeruginosa
Klebsiella sp.
Enterobacter sp.
Serratia sp.
Proteus mirabilis
Proteus indol, (+)
Escherichia coli
Citrobacter sp.
Clostridiuni perfringens
Candida albicans

Rates in%*

32.8
5.1
8.5
1.6
24.7
3.1
2.9
1.3
6.6
1.2
2.2
1.4
-
-

MIC** (mkg/ml)

100
50
12.5
100
50
100
50-100
100
50
1.56-50
50
50
100
100

*   Rates of the bacterial species in burn wounds infections
** MIC = Minimal inhibitory concentrations

Table I - Minimal inhibitorv concentrations of Flamazine against the most frequent pathogem in burns

The efficacy of Flamazine is due to the combination of the bacteriostatic effect of sulphadiazine with the bactericidal effect of silver. Clinical trials in large and small second- and third-degree burns degrees have demonstrated the high antibacterial activity of Flamazine, which delayed wound colonization in large burns until 10-14 days post-burn. These features indicate that Flamazine possesses most of the criteria necessary for the ideal local agent (Table 2).
Many publications proving the efficacy of Flamazine have appeared, but none concerning investigations conducted in Bulgaria. There are however some reports on the use of other silver sulphadiazine compounds (e.g. Dermazine) in our country.
The aim of this study was to assess the efficacy of Flamazine in the prevention of bacterial infection and in burn treatment.

Requirements of the ideal topical agent

Features of Flamazine

High activity against gram-positive negative bacteria, fungi and viruses (lack of bacterial resistance)

Fasy to apply and remove

Prolonged action

Good penetration into wounds and and eschars


Painless application; desirable analgesic effect

No adverse effect

 

No disturbance of epithelialization process

No discolouration of wounds

Not very expensive

High activity against and gramgram-positive and gram-negative bacteria, fungi and viruses (bacterial resistance rare)

Easy to apply and remove

Possibility of residual effect

Good penetration into wounds; not deep enough into eschars

Painless application; analgesic effect

Few, mild and transient adverse effects. No effect on serum electrolytes or acid balance of blood; possibility of prolonged use

No disturbance of epithelialization process

Discolouration of wounds

Relatively expensive

Table II - Requirements of the ideal topical agent and the corresponding features of Flamazine

Material and methods

We treated 50 hospitalized patients of either sex aged between I and 76 years, as well as 25 out-patients. The treatment lasted from 4 to 25 days. All the patients were hospitalized within 24 hr post-burn. In the out-patient group, the total body surface area (TBSA) burned was between I and 6% (second- and third-degree); in the inpatient group, TBSA ranged from 5 to 70% (also secondand third-degree) Table III presents the bacteriological results are reported of Flamazine application in 35 patients. The following aspects were considered:

  • the spectrum of bacteria before and after Flamazine application, at every change of dressing

  • the number of bacteria in I g of tissue, with a significant value of 101 bacteria per gram (b/g) accepted as the criterion for the development of local and systemic infection

After conventional cleansing of the wounds, we used the following two methods for the application of Flamazine.

Before treatment After treatment
Bacterial species Bacterial numbers Bacterial species Bacterial numbers
1 no growth 0 no growth 0
2 no growth 0 no growth 0
3 no growth 0 no growth 0
4 no growth 0 no growth 0
5 no growth 0 no growth 0
6 no growth 0 no growth 0
7 no growth 0 no growth 0
8 no growth 0 no growth 0
9 no growth 0 no growth 0
10 no growth 0 no growth 0
11 CNS <103 b/g P. aeruginosa + Acinetobacter sp. 6x104 b/g
12 CNS <103 b/g S. aureus 104 b/g
13 no growth 0 no growth 0
14 no growth 0 no growth 0
15 no growth 0 no growth 0
16 S. aureus 0 no growth 0
17 no growth 0 no growth 0
18 no growth 0 no growth 0
19 Acinetobacter sp. 2.5x104 b/g no growth 0
20 no growth 0 no growth 0
21 CNS 1.5x105 b/g no growth 0
22 no growth 0 no growth 0
23 no growth 0 no growth 0
24 S. aureus 104 b/g no growth 0
25 no growth 0 no growth 0
26 no growth 0 no growth 0
27 no growth 0 Serratia sp. <103 b/g
28 Enterobacter sp. 6.6x105 b/g Enterobacter sp. 1.1x104 b/g
29 no growth 0 no growth 0
30 no growth 0 no growth 0
31 no growth 0 no growth 0
32 no growth 0 no growth 0
33 no growth 0 no growth 0
34 no growth 0 no growth 0
35 no growth 0 no growth 0

CNS = coagulase-negative staphylococci
b/g = bacteria per gram

Table III - Bacteriological results of Flamazine application in 35 patients with second- and third-degree burns

Closed method
Flamazine was applied in a layer 2-3 mm thick directly on the burn wound by applicator or by hand in a sterile glove. It was then covered with dry sterile gauze. The burn wound was sometimes covered after a preliminary spread also with Flamazine sterile gauze. When the hands were burned, they were placed in a polythene bag or sterile latex gloves containing Flamazine. In this way the movements of the hands are painless and their observation is easy.

Open method
The open method is convenient for burns of the face and perineum. Flamazine was spread over the burned surfaces, which were left uncovered. The contact of the agent with the unburned skin was painless and safe. Dressings were changed in most cases every 24 hours during the first 10 days post-burn, and every 24-48 hours thereafter. When necessary, dressings were changed more frequently.
With the open method of treatment the agent could be changed more often, i.e. every 6-12 hours. The easiest and most painless way of removing Flamazine from the wound surface was to wash it out with sterile solution or water.

Results

Clinical observations
All the patients were cured: the out-patients and thirtyone of the in-patients after non-surgical treatment, and nineteen of the hospitalized patients after surgical treatment. Sixteen of these nineteen patients underwent early surgical necrectomy between days 3 and 6 post-burn, while the remaining three were operated on ten and more days after the accident. Spontaneous epithelialization of superficial burns took place in the generally accepted terms, in relation to the depth of the injury.

The maintenance of no or low-level bacterial contarnination of the wounds and the prevention of inflammation allowed early operative treatment and good epithelialization of the wounds.
According to our observations, the eschars in deep burns were soft, slightly moist, metal grey in colour, and with no inflammation area in or around them or any bacterial growth, this making it possible to perform early surgical necrectomy. When this was not done, the separation of the eschars was performed gradually, layer by layer, until full removement, without any sign of local infection.
With regard to superficial burns, after Flamazine application the wounds were covered with a heavy purulent exudation, which gave the false impression of a worsening of the burns appearance. The exudation was in fact sterile and simply the result of the wound exudation mixing with the topical drug. It was easy to remove and there was no sign of any real worsening of the wounds. Deep dermal burns were sometimes covered with a thin coating of Flamazine, mixed with proteins, dissolved in the wound exudation. These coatings were easily removed by scraping them away or cleaning up during subsequent medications. After repeated application of Flamazine the burn surfaces became fresh, with no unpleasant smell or any sign of infectious complications. This was due to inhibition of bacterial growth and the wounds improved condition. As a result, a good process of epithelialization initiated after debridement.

Microbiological results
The bacteriological results in 35 patients are presented in Table 3 and Fig. 1. It was established that:

  • in 27 patients (77.0%) the wounds remained without bacterial growth from the time of the patients' admission until the operation or epithelalization of the wounds in 4 patients (N° 16, 19, 21, 24) (11.5%) the preexisting bacteria were eradicated after Flamazine application, which means that the effect of the agent was both therapeutic and prophylactic
  • in one patient (N° 28) (2.9%) the bacterial quantity was reduced and after three medications (day 4) the pre-existing bacterial pathogens were eradicated

  • in three patients (N° 11, 12, 27) (8.6%) bacterial colonization of the wounds occurred as follows: Pseudomonas aeruginosa + Acinetobacter sp., days 3 to 5 (N° 11); Staphylococcus aureus, days 3 to 8 (N° 12); and Serratia sp., days 6 to 10 (N° 27). The bacterial quantities in all three cases were below the significant value; no clinical signs for local or systemic infection appeared, and the skin grafting and healing processes were not disturbed

three patients developed staphylococcal bacteraemia, due to Staphylococcus aureus in two patients and coagulase-negative staphylococei in one. The origin in each case was contaminated central venous can~ nulae; there were no cases of generalization of local infection (burn wound sepsis)
The results were evaluated as follows (Fig. 2):

  • very good - 31 cases (88.5%)

  • good - 4 cases (11.5 %)

  • unsatisfactory - no case

No toxic reactions or other side-effects were observed. The application of Flamazine was painless and comfortahle for the patients.

Fig. 1 - Bacteriological results of Flamazine treatment. Fig. 2 - Evaluation of treatment results.
Fig. 1 - Bacteriological results of Flamazine treatment. Fig. 2 - Evaluation of treatment results.

Conclusion

Our results demonstrate that Flamazine exerts a prophylactic and therapeutic action against wound infection in burns, which was proved both in vitro and in vivo. Considering that infection is the most frequent and life-threatening complication in patients with severe burns, we consider that local treatment with Flamazine is very important for the favourable course and outcome of the burn disease as it prepares deep burns for early operative treatment and promotes rapid epithelialization of superficial burns.

 

RESUME. La sulfadiazine argentée, utilisée pour la première fois par Fox en 1968, est aujourd'hui le médicament préféré pour le traitement local des brûlures, et Flarnazine, son composé le plus diffus, répond à la plupart des critères de l'agent local idéal. Le but de cette étude était d'établir l'efficacité de Flamazine dans la prévention de l'infection bactérienne et dans le traitement des brûlures. Les Auteurs ont considéré 50 patients hospitalisés des deux sexes, âgés d'un an jusqu'à 76, atteints de brûlures de deuxième et troisième degré en 570% de la surface corporelle. Les Auteurs présentent les résultats bactériologiques de l'application de Flamazine dans 35 patients. La Flamazine a été appliquée avec la méthode ou ouverte ou close. Tous les patients ont été traités avec succès. Dans les brûlures profondes les escarres étaient molles, légèrement humides, de couleur gris métallique, et sans la présence de zone d'inflammation ni de développement bactérien, ce qui permettait d'effectuer la nécrectomie chirurgicale précoce. Un bon processus d'épithélialisation a commencé après le débridement des brûlures superficielles. Dans 27 patients (77,0%) les lésions n'ont pas présenté aucun développement bactérien depuis le moment de l'hospitalisation jusqu'à l'opération chirurgicale ou l'épithélialisation. Les résultats bactériologiques ont été évalués comme très bons dans 31 cas (88,5%) et bons dans quatre (11,5%), sans aucun résultat peu satisfaisant. Les Auteurs concluent que le traitement local avec Flamazine est très important pour le cours positif et le bon résultat de la maladie des brûlés puisque ce médicament prépare les brûlures profondes pour le traitement chirurgical précoce et favorise l'épithélialisation rapide des brûlures superficielles.


BIBLIOGRAPHY

  1. Fox C., Jr: Topical therapy and the development of silver sulphadia zinc, Surg. Gynecol. Obstet., 157: 82-8, 1983.
  2. Ge Sheng De, Hu Zheng Lu., Cheng In Lin et al.: Experimental study on topical antimicrobial agents in burns. Burns, 13: 56-9,1987.
  3. Gillett A.P.: Antibiotic prophylaxis and therapy in burns. J. Hosp. it.Infect., 6 (Suppl. B), 59-66, 1985.
  4. Fakhry S.N., Alexander J., Smith D., Meyer A.A., Peterson H.D.:Regional and institutional variation in burn care. J. Burn Care Rehabil., 16: 86-90, 1995.
  5. Taddonio TE., Thomson P.D., Smith D.J., Prasad J.K.: A survey of wound monitoring and topical antimicrobial therapy practices in the treatment of burn injury. J. Burn Care Rehabil., 11: 423-7, 1990.
  6. Hermans R.P.,: Topical treatment of serious infections with special reference to the use of rnixure of silver sulphadiazine and cerium nitrate: two clinical studies. Burns, 11: 59-62, 1984.
  7. Kuroyanagi J., Kim E., Shioya N.: Evaluation of a synthetic wound dressing capable of releasing silver sulphadiazine. J. Burn Care Rehabit. 12: 106-115, 1991.
  8. Hoekstra MJ... Hupkens P., Dutrieux P. et al.: A comparative burn wound model in the New Yorkshire pig for the histopathological evaluation of local therapeutic regimens, silver sulphadiazine cream as a standard, Br. J. Plast. Surg., 93, 46: 585-9.
  9. Hoffmann S.: Silver sulphadiazine: an antibacterial agent for topical use in burns. A review of the literature. Scand. J. Plast. Reconstr. Surg., 18: 119-26, 1984.
  10. Modak S., Fox P., Standford J. et al.: Silver sulphadiazine impregnared biologic membranes as burn wound covers. J. Burn Care Rehabil., 7: 422-5, 1986.
  11. Sawhney C.P., Sharma R.K., Rao K.R., Kaushish R.: Long term experience with 1% topical silver sulphadiazine cream in the management of burn wounds. Burns 15: 403-6, 1989.
  12. Stem H.S.: Silver sulphadiazine and the healing of partial thickness burns: a prospecctive clinical trial, Br. J. Plast. Surg., 42: 581-5, 1989.
  13. Schiller W.R., Leukens C., Neve D.: The use of expanded polytetrafluoroethylene gloves for care of upper extremity burns. J. Burn Care Rehabil., 15: 34-6, 1994.

This paper was received on 7 November 1996.

Address correspondence to: Dr Ognian Hadjiiski,

Centre for
Burns and Plastic Surgery, Pirogov Medical Institute,
21 Macedonia Blvd., 1605 Sofia, Bulgaria (Tel./Fax: 00359.2.546108)




 

Contact Us
mbcpa@medbc.com