ORIGINAL CONTRIBUTION

Topical Antibiotic Ointment Versus Silver-

containing Foam Dressing for Second-degree
Burns in Swine
Jimmy Toussaint, PhD, Won Taek Chung, Naureen Osman, Steve A. McClain, MD, Vivek Raut, PhD,
and Adam J. Singer, MD

Abstract
Objectives: Second-degree burns are very common but their management is controversial. These burns
may be treated with either topical antimicrobial agents or advanced occlusive dressings; however, there
is no established treatment comparator for preclinical studies. This study was designed to determine
which of two commonly used comparator therapies (a silver-containing advanced dressing or a topical
antibiotic ointment) resulted in faster reepithelialization and less scarring. The hypothesis was that
second-degree burns treated with a topical antimicrobial ointment would heal faster and with less
scarring than those treated with a silver-containing occlusive foam dressing in a porcine model.
Methods: Deep partial-thickness burns were created on the flanks of three anesthetized female domestic
pigs (20 to 25 kg) using a 150-g aluminum bar preheated in 80°C water bath and applied to the skin for
20 seconds using a force of 2 kg. The burn eschars were excised 48 hours later with an electric
dermatome set at a depth of 0.75 mm. The wound beds were treated with a thin layer of triple-antibiotic
petrolatum-based ointment (changed three times weekly) or a silver-containing foam dressing (changed
once weekly). Full-thickness punch biopsies were obtained at 9, 11, 14, 16, 18, and 21 days for
determination of percentage complete wound reepithelialization and at 28 days for measurement of scar
depth.
Results: At all dressing changes the wounds treated with the topical antibiotic appeared moist, while
those treated with the silver-based dressings appeared dry. At day 21 all wounds treated with the
ointment were completely reepithelialized, while only 55% of those treated with the silver dressing were
reepithelialized (p < 0.001). Scar depth at day 28 was also significantly less in wounds treated with the
topical antibiotic ointment (4.3 mm vs. 5.1 mm, difference = 0.7 mm; 95% confidence interval [CI] = 0.1 to
1.4 mm). There was less scar contraction in wounds treated with the topical antibiotic compared with the
silver-based dressing (mean  SD = 25.0%  14.6% vs. 38.9%  16.9%, difference = 13.9%; 95% CI =
5.7% to 22.0%).
Conclusions: In this model of excised deep partial-thickness burns, a triple-antibiotic ointment enhanced
reepithelialization and reduced scar depth and contraction compared with a silver-based foam dressing.
This triple-antibiotic ointment should be considered as a control for studies evaluating novel topical burn
therapies.
ACADEMIC EMERGENCY MEDICINE 2015;22:927–933 © 2015 by the Society for Academic Emergency
Medicine

S
econd-degree (partial-thickness) burns are very
common, but their management is controversial.
These burns are usually treated with either a top-
ical antimicrobial cream or ointment or one of many
advanced, silver-containing occlusive dressings. Over
the past decade a large number of advanced burn
dressings have been introduced into the marketplace.
Many of these dressings contain silver due to its antimi-

From the Department of Emergency Medicine, Stony Brook University, Stony Brook, NY.
Received January 23, 2015; revision received March 4, 2015; accepted March 4, 2015.
This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Office of
the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under Con-
tract HHSO100201300020.
The authors have no relevant financial information or potential conflicts to disclose.
Supervising Editor: Shahriar Zehtabchi, MD.
Address for correspondence and reprints: Adam J. Singer, MD; e-mail: adam.singer@stonybrook.edu.

© 2015 by the Society for Academic Emergency Medicine ISSN 1069-6563 927
doi: 10.1111/acem.12723 PII ISSN 1069-6563583 927
928
crobial effects and relative safety.1 In most studies, these
dressings have been compared to silver sulfadiazine
(SSD), which is still the most commonly used burn dress-
ing worldwide.2 However, a large body of evidence sug-
gests that SSD actually has deleterious effects on
keratinocytes and delays wound reepithelialization.3–5
Thus, SSD is probably not the optimal comparator
when evaluating potentially new burn dressings or topi-
cal therapies.
Ideally, a novel therapy for burns should be com-
pared against the best comparator and not one that is
suboptimal. The current study was designed to compare
the effects of one of the most commonly used topical
therapies, a petrolatum-based triple-antibiotic ointment,
with one of the most commonly used silver-based foam
dressings, to determine the optimal comparator for
future studies, particularly in the porcine model. We
hypothesized that when compared with the silver-based
dressing, the ointment-based antibiotic would speed re-
epithelialization and reduce the depth of scarring in a
porcine partial-thickness burn model.
METHODS
Study Design
This was a prospective, randomized controlled study.
The study was approved by the Institutional Animal
Care and Use Committee. All animals were handled in
accordance with the guidelines issued by the National
Research Council.6
Animals Care and Preparation
Three female Yorkshire pigs weighing 20 to 25 kg were
used for the study. The animals were acclimated for
7 days prior to surgery. The animals were housed in
separate pens and fed with a diet of Purina Mills Lab
Diet food 5083 (Fisher and Sons) and given water ad
lib. The animals were subjected to daily cycles of dark
(12 hours) and light (12 hours).
Sedation, Anesthesia, and Analgesia. The animals
were fasted overnight and sedated with a combination
of acepromazine 0.1 mg/kg, atropine 0.02 mg/kg, keta-
mine 20 mg/kg, and xylazine 2.2 mg/kg, by intramuscu-
lar injection. The pigs were endotracheally intubated
and maintained under a surgical plane of anesthesia
with isoflurane 1.0% to 5.0% mixed with oxygen. The
concentration of isoflurane was titrated to ensure ade-
quate anesthesia while avoiding hypoventilation and
apnea. A 50-lg fentanyl transdermal patch was applied
topically following the burn creation and after each
punch biopsy for pain control both immediately after
and for the 3 days immediately following the proce-
dures. Buprinorphine 0.02 mg/kg was injected intra-
muscularly during the procedure and after the
procedure as needed based on assessments for pain or
discomfort (e.g., vocalization, mobilization, feeding)
made by the veterinarian staff throughout the entire
study.
Study Protocol
Burn Creation and Local Treatment. The flank and
back hair were clipped with electric clippers and the
Toussaint et al. • TOPICAL ANTIBIOTIC VS. DRESSING FOR BURNS
skin was scrubbed with soap and water. A rolled towel
was placed under the lower abdomen of the animal to
reduce a sway or lumbar lordosis during the wounding
procedure.
A previously validated deep partial-thickness porcine
burn model was used in this study.7 While under anes-
thesia, 20 deep partial-thickness burns were created
using a 2.5 9 2.5 9 7.5-cm 150-g aluminum bar pre-
heated in a water bath to 80°C (Figure 1). Prior to creat-
ing the burns, the location of the burns was traced with
a pen using a template that ensured that the horizontal
distance between the columns of burns was at least
2 cm and that the vertical distance between the rows of
burns was at least 4 cm. Four columns of five burns
each were created adjacent to the spinous processes of
the vertebral bodies over the paravertebral muscles that
served as a firm surface upon which the burns were
created. The aluminum bar was blotted dry so as not to
cause a burn from steam or scalding and then applied
perpendicular to the skin surface, with a 2-kg pressure
load for a period of 20 seconds.8 This type of injury cre-
ates a deep partial-thickness burn that involves approxi-
mately 50% of the thickness of the pig’s dermis. After a
burn was created, the surface of the aluminum bar in
contact with the skin was wiped with an alcohol swab
to remove any adherent debris. The bar was then
placed back in the water bath for at least 2 minutes to
allow proper temperature equilibration for the next
burn.
Following the burning procedure, the necrotic epider-
mis was gently removed from the surface of the burns
by scraping the burn with the blunt handle of a forceps.
This is done to replicate rupture and subsequent
removal of the burn blister in humans, since burns in
pigs do not form blisters, possibly due to their dense
skin.9 Two days after injury, the burn eschar was
excised with an electric dermatome (Integra Lifescienc-
es, Padgett Instruments, Plainsboro, NJ) set at a depth
of 0.75 mm comprising the upper necrotic dermal layer
(Figure 2). This procedure was performed to simulate
tangential excision and to enhance the contact of any
topical therapies with the underlying tissue. After burn
injury, the burns were randomized to a commercially
available petrolatum-based topical triple antibiotic (Neo-
sporin, Polysporin, bacitracin) or a silver-based foam
dressing (Mepilex Ag, Mo € lnlycke Health Care, Guthen-
Figure 1. Image of burns immediately following their creation.
ACADEMIC EMERGENCY MEDICINE • August 2015, Vol. 22, No. 8 • www.aemj.org
Figure 2. Removal of burn eschar with electric dermatome.
burg, Sweden). To prevent migration of the topical
treatments from one wound to an adjacent one, the
burns were treated with the same treatment across the
entire horizontal row of burns. In the first pig, determi-
nation of which of the horizontal rows of wounds
(n = 4) was to receive each of the experimental treat-
ments was determined using a random numbers table.
Subsequently, in each of the next animals the treatment
rows were sequentially rotated to ensure an even distri-
bution of wounds in a cephalocaudal direction, since
this may affect healing.
Dressing changes and reevaluation of the burns was
performed three times weekly (Monday, Wednesday,
Friday) for the entire duration of the study after sedat-
ing and anesthetizing the pigs as stated previously. Both
treatments were applied immediately after burn injury
and after dermatomal excision of the eschars. Prior to
reapplication, each wound was gently scrubbed with
soap and warm water. The topical antibiotic was reap-
plied three times weekly while the silver-based dressing
was reapplied once weekly (as recommended by the
manufacturer) until the end of the experiment. After
application of the topical antibiotic, the wound was cov-
ered with a nonadherent dressing (Telfa, Kendal Health-
care Products Company, Mansfield, MA) and a
polyurethane dressing (Tegaderm, 3M Health Care, St.
Paul, MN). All wounds were then covered by a gauze
wrap (Sof-Form, Medline Industries Inc., Mandelein, IL)
and adhesive bandage (Tensoplast, BSN Medical S.A.A.,
Vibraye, France). The animals were euthanized with a
lethal dose of barbiturate after completion of the 28-day
experiment.
Histopathology. All biopsies were alcohol-dehydrated,
xylene-cleared, and paraffin-embedded. The biopsies
were sectioned at 5-lm intervals and stained with hema-
toxylin phloxine saffron.10 A board-certified dermatopa-
thologist, masked to treatment assignment, evaluated all
tissue sections using standard light microscopy.
Outcomes
Digital images of the wound were obtained with a
digital camera (Nikon, Coolpix) without flash at every
dressing change and at the end of the experiment. Full-
thickness 4-mm punch biopsies were performed at 9,
11, 14, 16, 18, and 21 days after injury to determine the
percentage of completely reepithelialized wounds. This
929
outcome has very high reliability (r = 0.99).11 An 8-mm
full-thickness punch biopsy was taken from the center
of the wounds at the end of the study, 28 days after
injury, for determination of scar depth. Burn depth was
determined by averaging three measurements of the
vertical distance from the basement membrane to the
deepest level of the burns at the center and at the two
ends of the tissue slide.
Scar contraction was calculated by tracing the scar
perimeter from digital images of the wound on day 28
taken immediately before tissue sectioning and euthana-
sia, using Image J software (NIH, Bethesda, MD). The
percentage of wound contraction was determined by
subtracting the scar surface area at day 28 by the origi-
nal size of the burn, dividing this by the original burn
size, and multiplying by 100.
Data Analysis
The primary outcome was the percentage of completely
reepithelialized wounds at day 21, which was compared
between groups with the chi-square and Fisher’s exact
tests. A Kaplan-Meier analysis was also performed
using the log-rank test to determine changes in reepi-
thelialization over time in the two study groups. A
secondary outcome was scar depth 28 days after burn
injury. The level of significance was set at 0.05. Multivari-
ate analysis was performed to adjust for any within-pig
clustering. A sample size of 20 burns in each treatment
group has 80% power to detect a 25 percentage point
difference between the treatment groups in the percent-
age of completely reepithelialized burns.
RESULTS
A total of 60 burns were created, 20 on each of the
three experimental animals (Figure 1). Thirty burns
were randomized to triple antibiotics, and 30 were ran-
domized to the silver-based dressing.
On gross visualization, wounds treated with the topi-
cal antibiotic ointment remained moist and pink
throughout the entire duration of the experiment. In
contrast, wounds treated with the silver-based dressing
appeared dry and desiccated as early as the first dress-
ing change at day 2, even before dermatomal excision
of the eschar (Figure 3). By 21 days, all of the wounds
treated with the topical antibiotic appeared completely
reepithelialized, while only some of the wounds treated
with the dressings were completed reepithelialized.
On microscopy, wounds treated with the topical anti-
biotic reepithelialized more rapidly than those treated
with the silver-based dressing (Figures 4 and 5). At day
21, all wounds treated with the topical ointment were
completely reepithelialized, while the percentage of
completely reepithelialized wounds treated with the
silver-based dressing was only 55% (mean difference =
45%, 95% confidence interval [CI] = 20% to 66%; Figure 4).
A Kaplan-Meier analysis of time to reepithelialization also
showed a significant difference in the time to complete
reepithelialization using the log-rank test (p < 0.001,
Figure 5). Multivariate analysis adjusting for within-pig
clustering found that despite a pig effect, there was still
a significant treatment difference between the two study
groups (data not shown).
930
Figure 3. Comparison of burns 2 days after injury, prior to der-
matomal excision. Burns treated with the topical ointment are
pink and moist (left two columns). Burns treated with the silver
dressing are dry and covered with an eschar (right two col-
umns).
Figure 4. Representative micrographs of wounds treated with
topical antibiotic and silver dressing 21 days after injury. The
wound on the top (topical ointment) is completely reepithelial-
ized. The wound on the bottom (silver dressing) is only partially
reepithelialized.
The depth of scarring at 28 days after injury was sig-
nificantly less for wounds treated with the topical antibi-
otic, compared with the silver-based dressing (4.3 mm
vs. 5.1 mm, difference = 0.7 mm, 95% CI = 0.1 to 1.4;
Figure 6). There was also less scar contraction with
wounds treated with the topical antibiotic compared
with the silver-based dressing (mean  SD =
25.0%  14.6% vs. 38.9%  16.9%; difference = 13.9%;
95% CI = 5.7% to 22.0%; Figure 7). Of all burns, only
one developed a wound infection (Figure 8) at day 9
that resolved by day 11. This burn was treated with the
silver-based dressing.
DISCUSSION
Pigs are most commonly used in preclinical burn stud-
ies, because their skin most closely resembles that of
Toussaint et al. • TOPICAL ANTIBIOTIC VS. DRESSING FOR BURNS
humans.12 However, the choice of the control compara-
tor is not uniform, making comparisons among various
therapies or agents difficult, if not impossible. Most ani-
mal and human studies that have evaluated novel topi-
cal therapies and dressings have chosen SSD as the
comparator, since this treatment is still the most com-
monly used in burn services worldwide.2 However, the
evidence is clear that SSD delays reepithelialization.3–5
As a result, most studies that use SSD as the control or
comparator are biased in favor of the new treatment
and almost always demonstrate that the novel therapy
is superior to SSD.13,14 It is our belief that to demon-
strate superiority or even noninferiority, any therapy
studied should be compared to an optimal comparator
or standard of care. Because advanced silver-based
dressings or petrolatum-based topical antibiotic oint-
ments are often used but have not been directly com-
pared head to head, we designed the current study to
determine which was more effective in a previously vali-
dated porcine partial-thickness burn model.
Our results clearly demonstrate that a petrolatum-
based triple-antibiotic ointment applied three times a
week results in more rapid reepithelialization and less
scarring when compared to a frequently used advanced
silver-based foam dressing in the porcine model when
applied once weekly in a manner similar to its use in
humans. These results are most likely due to the fact
that wounds treated with the ointment remained moist
throughout the study period, while wounds treated with
the dressing dried out and became desiccated. A large
body of evidence has clearly demonstrated that a moist
wound environment optimizes healing.15 The fact that
the burns treated with the topical ointment remained
moist may be due to the fact that treatments were chan-
ged more frequently with the topical ointment than with
the dressings. However, the silver-based dressings were
specifically designed to require fewer and less frequent
dressing changes than topical therapies.
Our results, in which a petrolatum-based ointment
fared well, are in agreement with a recent systematic
review of nearly 100 studies on wound dressings for
both acute and chronic wounds, which concluded that
there was no evidence that any of the modern dressings
(including those containing silver) was better than
another, or better than saline or paraffin gauze, in terms
of general performance criteria.16 While the differences
in time to reepithelialization found in our study are
large and clearly of clinical relevance, the clinical signifi-
cance of the 0.7-mm difference in scar thickness and
14% difference in scar contraction at 28 days between
the two study groups is unclear. Other distinct advanta-
ges of the triple-antibiotic ointment are the fact that it is
readily available without a prescription, inexpensive,
and cosmetically more appealing than an opaque film or
cream, and there is no need for an overlying dressing
on areas such as the face.
Our results differ from those by Olson et al.17 who
compared the healing of small (1 9 1-cm) superficial
(0.4-mm) donor site wounds in pigs treated with petro-
latum-impregnated gauze dressings or saline-moistened
silver-based dressings and found faster reepithelializa-
tion with the silver-based dressings. Wounds dressed
with moistened silver-coated dressings reepithelialized
ACADEMIC EMERGENCY MEDICINE • August 2015, Vol. 22, No. 8 • www.aemj.org 931

Figure 5. Kaplan-Meier curve for time to complete reepithelialization.

Figure 6. Representative micrographs of wounds 28 days after injury demonstrating more superficial scars in wounds treated with
the topical ointment (left), compared with those treated with the silver dressing (right).

significantly more quickly. This resulted in complete re-
epithelialization within 70% of the time taken by those
wounds dressed with petrolatum gauze. This donor site
study used a silver-coated dressing composed of an
absorbent rayon/polyester core sandwiched between
two pieces of nanocrystalline silver-coated high-density
polyethylene mesh, which was moistened with saline
every day for a period of 10 days. However, the need to
constantly moisten the dressing negates one of its great
advantages, that being the need for infrequent dressing
changes.
The major difference between our study and the
study by Olson et al. is that we evaluated burn wounds
and not donor sites. Furthermore, the silver dressings
used were different. However, we specifically chose the
Mepilex dressing because it is the most commonly used
silver-based dressing in clinical use for burns and does
not require frequent wetting to maintain its effective-
ness. Finally, our study included a petrolatum-based
ointment that contained antibiotics, whereas Olson et al.
used a non–antibiotic-containing petrolatum-impreg-
nated dressing.
LIMITATIONS
The current study evaluated deep partial-thickness
burns that were tangentially excised. Whether or not
our results would be similar in nonexcised deep partial-
thickness burns or in deeper or more superficial burns
is unclear but likely. Furthermore, it is unclear if these
findings are generalizable to humans whose burns gen-
erally have more exudate than porcine burns, which
would reduce or prevent desiccation under the foam
dressing. Indeed, a recent human study by Silverstein
et al.18 concluded that the same silver-containing soft
silicone foam dressing that was used in our study
932 Toussaint et al. • TOPICAL ANTIBIOTIC VS. DRESSING FOR BURNS

Figure 7. Gross appearance of wounds 28 days after injury. The wounds on the left are less contracted and were treated with the
topical ointment. The wounds on the right were treated with the silver dressing and are more contracted.

when treated with a petrolatum-based topical antibiotic

ointment than when treated with a silver-based foam
dressing when used as clinically suggested. We believe
that the topical ointment should be considered as a con-
trol or comparator in future preclinical studies.

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Figure 8. Drainage of pus on day 9 from burn treated with sil-
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dressings.
CONCLUSIONS
We have shown that deep partial-thickness porcine
burns that are excised heal faster and with less scarring
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