Burns 31 (2005) 874–877

www.elsevier.com/locate/burns

Comparison of silver-coated dressing (ActicoatTM), chlorhexidine

acetate 0.5% (Bactigrass1), and fusidic acid 2% (Fucidin1)
for topical antibacterial effect in methicillin-resistant
Staphylococci-contaminated, full-skin thickness rat burn wounds
Ersin Ülkür a,*, Oral Oncul b, Huseyin Karagoz a, Esma Yeniz b, Bahattin Çeliköz a
a
Gulhane Military Medical Academy and Medical Faculty of Haydarpasa Training Hospital,
Department of Plastic and Reconstructive Surgery and Burn Unit, Istanbul, Turkey
b
Gulhane Military Medical Academy and Medical Faculty of Haydarpasa Training Hospital, Department of Infectious diseases, Istanbul, Turkey
Accepted 1 May 2005

Abstract

ActicoatTM, chlorhexidine acetate 0.5%, and fusidic acid 2% were compared to assess the antibacterial effect of an application on
experimental 15% BSA, full-thickness burn wounds in rats swabbed 24 h earlier with a 108 standard strain of methicillin-resistant Staphylococci.
The swabbed organism was recovered from the eschar of all groups except the fusidic acid group. While there were significant differences
between treatment groups and control group, the mean eschar concentrations did not differ significantly between the Acticoat and
chlorhexidine acetate groups, but there were significant differences between the fusidic acid group and the other treatment groups.
There were no statistically significant differences between treatment groups, and between control group and the chlorhexidine acetate
group regarding recovery of the seeded organism from muscle, but there were significant differences between the control group and Acticoat
group, and between control the group and the fusidic acid group. While no systemic spread was seen in the treatment groups, it was seen in six
animals in the control group.
The animal data suggest that fusidic acid is the most effective agent in the treatment of methicillin-resistant Staphylococcus aureus-contaminated
burn wounds, and Acticoat is a choice of treatment with the particular advantage of limiting the frequency of replacement of the dressing.
# 2005 Elsevier Ltd and ISBI. All rights reserved.

Keywords: Burn treatment; Silver; Chlorhexidine acetate; Fusidic acid

1. Introduction been a significant cause of morbidity and mortality among

Infection is still a leading cause of morbidity in burn
patients, although major advances have been achieved in
burn wound management [1]. Infection impedes wound
healing by damaging tissue and promoting inappropriate and
excessive inflammation [2]; therefore, infection control is
still very important in burn wound care. Methicillin-resistant
Staphylococcus aureus (MRSA)-contaminated wounds have
* Corresponding author at: GATA Haydarpasa Egitim Hastanesi Plastik
ve Rekonstruktif Cerrahi Klinigi ve Yanık Unitesi, Üsküdar, Istanbul,
Turkey. Tel.: +90 216 346 26 00x2656/532 470 76 59;
fax: +90 216 348 78 80.
E-mail address: eulkur@yahoo.com (E. Ülkür).
thermally injured patients since the 1980s [3]. Numerous
topical antibacterial agents, such as ActicoatTM, chlorhex-
idine acetate 0.5%(CA), and fusidic acid (FA) 2% are
available for clinical use with various efficacies against
MRSA [4–6]. The potential threat for effective control of
MRSA among the burn patients is the emergence of bacterial
resistance to topical and systemic antibacterial agents. Since
resistance patterns to MRSA change from one burn center to
other, each center should monitor the developing resistance
profiles in order to use proper appropriate agents.
To our knowledge, there is no report that compares the
activities of ActicoatTM, chlorhexidine acetate 0.5%, and
fusidic acid 2% against MRSA on a burn wound model. We
present a study comparing of these agents efficacies in

0305-4179/$30.00 # 2005 Elsevier Ltd and ISBI. All rights reserved.

doi:10.1016/j.burns.2005.05.002
 E. Ülkür et al. / Burns 31 (2005) 874–877
treating a rat full-skin thickness burn wound seeded 24 h
earlier with a standard strain of MRSA.
2. Material and methods
Male Wistar rats (n = 32) weighing 200–230 g were used
and housed under standard conditions at ambient room
temperature and given laboratory chow and water ad libitum
throughout the study. The experimental protocol was
approved by the Ethical Committee of the Haydarpasa
Training Hospital before commencement of the study.
The weights of the animals were measured. They were
anesthetized intraperitoneally with ketamine hydrochloride
(80 mg/kg body weight), and their backs were shaved. They
received a full-skin thickness dorsal scald burn in boiling water
for approximately 15% of the body surface by a standard
method [7]. The animals were resuscitated with an
intraperitoneal injection of 2 ml of lactated Ringer’s solution.
Ten minutes after the burn, each animal was seeded with
0.5 ml of broth containing 1  108 colony-forming units
(CFU) of MRSA (ATCC 38591) by swabbing. The animals
were placed in separate sterilized cages and allowed to
recover.
After 24 h, the animals were assigned at random to four
groups. Group 1 was the control group, and no topical agent
was applied. Group 2 was the silver-containing dressing
(ActicoatTM, Smith and Nephew, Istanbul, Turkey)-treated
group, Group 3 was the 2% fusidic acid (Fucidin1, Abdi
Ibrahim, Istanbul, Turkey), and Group 4 was the 0.5%
chlorhexidine acetate (Bactigras1, Smith and Nephew,
Istanbul, Turkey)-treated group. Treatment started at 24 h
post-burn. ActicoatTM and CA were applied to the wounds as
the same sizes as the wounds. Sterile gauze were placed over
them and all the dressings were attached with skin staplers.
The ActicoatTM patches of dressing was wetted with
distilled water three times a day, and changed every other
day. The CA dressing was changed once daily. FA was
applied liberally to the burn wound with a sterile tongue
blade once daily. No dressing was applied.
All the animals were anesthetized and killed on day 7
post-burn and their weights were measured. A loss of more
than 15 g (7.5%) was considered indicative of systemic
Fig. 1. The frequency of recovery of seeded MRSA from the groups and development of systemic infection (FA: fusidic acid, CA: chlorhexidine acetate,
MRSA: methicillin-resistant S. aureus).
875
disease. All the cultures were obtained using an aseptic
technique. Initially, thoracotomy was performed. Blood
cultures were obtained from the left ventricle, and lung
biopsies were obtained. Blood specimens were cultured on
5.0% sheep blood agar and lung specimens placed in brain
heart infusion broth; both were incubated at 35 8C degrees
and isolated organisms were identified by standard methods.
Full-skin thickness 9 mm punch biopsies were obtained
from the center of the burn eschar. After removal of eschar
and underlying fascia, a separate biopsy of paravertebral
muscle deep to the burn eschar was obtained. Separate
quantitative cultures of eschar and muscle were performed
using a standard method [8].
The mean and standard deviation of counts for each
treatment group were determined. The package program
SPSS (Statistical package for Social Sciences for Windows
7.0) was used for statistical analysis. Kruskal–Wallis and
Mann–Whitney U-tests were used to compare means and
standard deviations of the values of groups. Differences in
response between groups were compared by x2 analysis of
Fisher’s exact probability test. The incidence of recovery of
the seeded organism from muscle, lung and blood and
development of systemic infection was compared by x2
analysis. Probability levels less then 0.05 were considered
significant.
3. Results
No animal deaths were recorded throughout the experi-
mental protocol. The frequency of recovery of the seeded
organisms from each culture site is detailed in Fig. 1. A
comparison of quantitative cultures performed on burn eschar
is shown in Fig. 2. Kruskal–Wallis variance analysis of the
groups (for burn eschar columns) was significant ( p < 0.05).
Paired comparison of the groups was performed by Mann–
Whitney U-test. There were significant differences between
treatment groups and the control group ( p < 0.05), and
between the FA group and the other treatment groups
( p < 0.05). The differences according to the organisms
recovered from muscle were significant between the control
group and the Acticoat group, and between control group and
FA group ( p < 0.05, x2 analysis).
876 E. Ülkür et al. / Burns 31 (2005) 874–877
Fig. 2. Concentrations of seeded MRSA (CFU/ml) recovered from the
eschar (FA: fusidic acid, CA: chlorhexidine acetate, MRSA: methicillin-
resistant S. aureus).
The appearance of organisms other than seeded the
organism was not seen in this study.
4. Discussion
The patient suffering major burns is at risk from both
cutaneous and systemic infection. Prior to the routine use of
topical anti-microbial agents, burn wound sepsis was listed
as cause of death in 60% of burn patient deaths [5]. Using the
most effective topical agent is very important for the patient
suffering major burn.
MRSA is a pathogen of special concern in intensive care
units. The burn units are a very susceptible habitat for
colonization and infection events by this organism. In our
unit, MRSA is one of the most frequent pathogens recovered
from cultures. In the present study, we devised an
experimental protocol to investigate which topical agent
usage is the most logical and effective to eliminate MRSA
from our burned patients.
Silver in its numerous forms has been used for over 200
years in the treatment of burn injury [9]. Silver nitrate, silver
sulfadiazine, silver calcium phosphate, and metallic silver
film have been used for many years in burn treatment. Tissue
irritation by silver nitrate and inactivation of much of the
silver by wound fluid and formation of a pseudo-eschar for
silver sulfadiazine are some limitations for using silver
products in burn topical treatment [10]. New silver-
impregnated dressings such as ActicoatTM we designed to
overcome these limitations. Silver exerts its antimicrobial
effects by interfering with the respiratory chain at the
cytochrome level [11], and interfering with components of
the microbial electron transport system [12]. Silver is
effective against a broad range of aerobic, anaerobic, Gram-
negative and Gram-positive bacteria, yeast, filamentous
fungi, and viruses [13,14]. Early silver formulations lose
their silver ions in a short time, so that the frequent
replacement is required. For example in burn unit, silver
sulfadiazine is commonly applied twice a day and silver
nitrate up to 12 times a day, with all of the mechanical
trauma and discomfort that this can cause to a patient. It was
also reported that MRSA is more susceptible to ActicoatTM
than the other silver-containing products [10]. In the present
study, the results showed that ActicoatTM had an effect to
limit MRSA on the eschar and prevent systemic spreading,
but it did not have an effect to remove the MRSA from the
eschar as did FA. However, ActicoatTM has an advantage of
efficiently limiting the frequency of replacement of the
dressing. The important disadvantage for using ActicoatTM
in major burns is the cost.
FA is an antibiotic isolated from culture media of the
fungus Fusidium coccineum. It has a narrow bacterial
spectrum, mainly against Gram-positive bacteria; there is
exceptionally high in vitro activity against S. aureus. Its
topical form has been effectively used in primer and
secondary skin infections [15]. Although Staphylococcal
resistance to FA has been documented [16,17], in vitro
evidence suggests that resistance to S. aureus is less likely to
occur after exposure to high concentration of FA, reflecting
the situation with topical use [18]. Although there are some
reports about the priority of using mupirocin for S. aureus
infections [19,20], it was found to be costly for treatment of
MRSA in major burn patients [6]. In the present study, FA
acted more effectively than the other agents in removing the
MRSA from the eschar.
CA is another skin antiseptic choice that we use very
often in the burn treatment. CA is effective against most
Gram-positive and Gram-negative bacteria, and some fungi
[21]. In the present study, CA had the same effect as Acticoat
to prevent the systemic spread of MRSA, but deep invasion
of the MRSA to the muscle was not be prevented by CA.
As a conclusion, the animal data suggest that FA is the
most effective agent in the treatment of MRSA-contami-
nated burn wounds, and Acticoat is a treatment of choice
with the advantage of limiting the frequency of replacement
of the dressing.
References
[1] Greefield E, McManus AT. Infection complication: prevention and
strategies for their control. Nurs Clin North Am 1997;32:297–309.
[2] Wiseman DM, Rovee DT, Alvarez OM. Wound dressings: design and
use. In: Cohen IK, Diegelman RF, Lindblad WJ, editors. Wound
healing: biochemical & clinical aspects. Philadelphia: WB Saunders;
1992. p. 562–600.
[3] Gang RK, Sanyal SC, Bang RL, Mokaddas E, Lari AR. Staphylo-
coccal septicemia in burns. Burns 2000;2:359–66.
[4] Acıkel C, Oncul O, Ulkur E, Bayram I, Celikoz B, Cavusoglu S.
Comparison of silver sulfadiazine 1%, mupirocin 2%, and Fusidic acid
2% for topical antibacterial effect in methicillin-resistant staphylo-
cocci-infected, full-skin thickness rat burn wounds. J Burn Care
Rehabil 2003;24:37–41.
[5] Fraser JF, Bodman J, Sturgess R, Faoagali J, Kimble RM. An in vitro
study of the anti-bacterial efficacy of a 1% silver sulphadiazine and 0.2
chlorhexidine Digluconate cream, 1% silver sulphadiazine cream and
a silver coated dressing. Burns 2004;30:35–41.
[6] Smoot EC, Kucan JO, Graham DR, Barenfanger JE. Susceptibility
testing of topical antimicrobials against methicillin-resistant Staphy-
lococcus aureus. J Burn Care Rehabil 1992;13:198–202.
 E. Ülkür et al. / Burns 31 (2005) 874–877
[7] Walker HL, Mason AD. A standard animal burn. J Trauma
1968;8:1049–51.
[8] Heggers JP, Hawkins H, Edgar P, Villarreal C, Herndon DN. Treatment
of infection in burns. In: Herndon DN, editor. Total burn care. 2nd ed.
London: WB Saunders Company Ltd; p. 120.
[9] Klasen HJ. Historical review of the use of silver in the treatment of
burns. I. Early uses. Burns 2000;26:117–30.
[10] Dunn K, Edwards-Jones V. The role of ActicoatTM with nanocrystal-
line silver in the management of burns. Burns 2004;30(Suppl. 1):S1–9.
[11] Bragg PD, Rainnie DJ. The effect of silver ions on the respiratory
chain of E. coli. Can J Microbiol 1974;20:883–9.
[12] Modak SM, Fox CL. Binding of silver sulphadizine to the cellular
components of Pseudomonas aeruginosa. Biochem Pharmacol
1973;22:2391–404.
[13] Wright JB, Lam K, Hanson D, Burrel RE. Efficacy of topical silver
against fungal burn wound pathogens. Am J Infect Control
1999;27:344–50.
[14] Fox C. Silver sulphadiazin: a new topical therapy for pseudomonas in
burns. Arch Surg 1968;96:184.
877
[15] Winkelman W, Gratton D. Topical antibacterials. Clin Dermatol
1989;7:156–62.
[16] Shanson DC. Clinical relecance of resistance to Fusidic acid
in Staphylococcus aureus. J Antimicrob Chemother 1990;25:
15–21.
[17] Faber M, Rosdahl VT. Susceptibility to Fusidic acid among Danish
Staphylococcus aureus strains and fusidic acid consumption. J Anti-
microb Chemother 1990;25:7–14.
[18] Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of
infectious diseases. New York: Churcill Livingstone; 1995. p. 428.
[19] Gilbert M. Topical 2% versus 2% fusidic acid ointment in the
treatment of primary and secondary skin infections. J Am Acad
Dermatol 1989;20:1083–7.
[20] White DG, Collins PO, Rowsell RB. Topical antibiotics in the treat-
ment of superficial skin infections in general practice-a comparison of
mupirocin with sodium fusidate. J Infect 1989;18:221–9.
[21] Rosenberg A, Alatary SD, Peterson AF. Safety and efficacy of the
antiseptic chlorhexidine gluconate. Surg Gynecol Obstet 1976;143:
789–92.