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Exploring the effects of silver in wound management - What is optimal?

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  • DDRC Wound Care
  • Hertfordshire
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Exploring the effects of silver in wound management - What is optimal?

Abstract

There has been a vast increase in the last 5 years in the number of available silver-containing dressings. Their use has seen a corresponding rise in the number of publications referring to silver and its potential benefits. It is important that recognition is also given to the potential pitfalls of use, particularly in relation to toxicity. These factors have been recently reviewed. This article will explore what happens once the body absorbs silver, discuss the relevance of the carrier dressing to efficacy of silver, and review the clinical relevance of microbial kill time.
Vol. 18, No. 11
November 2006
307
Original Research
Exploring the Effects of Silver in
Wound Management—What is Optimal?
Richard White, PhD,
1
and Keith Cutting, MN, RN, Dip N, Cert Ed
2
From the
1
Department of Tissue Viability, Aberdeen Royal Infirmary, Aberdeen, Scotland, and
2
Buckinghamshire
Chilterns University College Buckinghamshire, United Kingdom
WOUNDS 2006;18(11):307–314
Abstract: There has been a vast increase in the last 5 years in the number of available silver-con-
taining dressings. Their use has seen a corresponding rise in the number of publications referring to sil-
ver and its potential benefits. It is important that recognition is also given to the potential pitfalls of use,
particularly in relation to toxicity. These factors have been recently reviewed. This article will explore
what happens once the body absorbs silver, discuss the relevance of the carrier dressing to efficacy of
silver, and review the clinical relevance of microbial kill time.
I
I
n recent years, use of silver in medical
healthcare devices has seen a vast increase.
This increase has been largely dominated by
wound dressings. Silver sulfadiazine, which has
been available for approximately 40 years, pro-
vides broad-spectrum antimicrobial activity and
has been widely used, particularly as a topical
cream to manage burn infection. In the last 5
years, the number of available silver-containing
dressings has increased. These dressings are used
primarily on chronic wounds and in clinical prac-
tice are regularly applied for periods of time up
to and in excess of 4 weeks. As silver dressings
may be used in clinical situations other than as a
temporary option, it is important that potential
toxicity be considered, particularly in relation to
the type and amount of silver, and as regards the
risk of selecting for bacterial resistance. These fac-
tors have been recently reviewed.
1
This article will consider what happens once
the body absorbs silver and discuss the levels of
silver required to exert a toxic effect on bacteria.
Address correspondence to:
Keith F. Cutting, MN, RN, Dip N, Cert Ed, Buckinghamshire Chilterns University College, Buckinghamshire, Chalfont
St. Giles, HP8 4AD United Kingdom
Phone: 011 44 1494 605172; Fax: 011 44 1494 605174; E-mail: info@healthdirections.co.uk
In addition, it will explore the relevance of the
c
arrier dressing to efficacy of silver and the clini-
cal relevance of microbial kill time. It is preferable
that any testimony made in respect of silver
should be clinically relevant. In order to do this,
data should be drawn from clinical (in-vivo) stud-
ies wherever possible. Unfortunately, few such
studies exist, so much data will be drawn from
available
in-vitro, ex-vivo, and animal studies.
Metabolic fate of topical silver. Silver, as a
component of wound dressings, antibiotic cream,
and first-aid plasters, comes into contact with
intact skin and breached skin on an increasingly
regular basis. The penchant for silver as an
antimicrobial has seen it incorporated into simple
adhesive dressings for minor cuts and abrasions
and is no longer reserved for “serious” wound
management. Potential repercussions associated
with these applications need to be acknowledged
and explored. Apart from increasing the risk of
contact dermatitis and selecting for resistance,
there will be concerns about possible systemic
and cutaneous toxicity. The interaction of metallic
silver with intact skin does not cause any
detectable increase in blood levels and is not of
great toxicological interest. However, the recent
increase in the use of silver-based wound treat-
ments raises some concerns about the systemic
effects of silver and warrants a toxicological
review. Several factors influence the capacity of a
metal to produce either local or systemic toxic
effects. These factors include 1) the degree of
absorption as influenced by solubility of the
metal or its compounds, 2) the ability to bind to
biological sites, and 3) the degree to which the
metal complexes are sequestered, metabolized,
and ultimately excreted.
Silver is applied to open, dermal wounds in
the form of inorganic silver salts (eg, silver
nitrate), metallic silver, or as organic compounds,
such as silver sulfadiazine (SSD).
2
The chemical
nature of the applied silver will influence its
absorption, distribution, and metabolism. Studies
on “background” or environmental silver levels
in human tissues have been conducted.
3,5,6
Normal
silver concentration is very low. Concentrations
of silver in blood, urine, liver, and kidney of sub-
jects without industrial or medicinal exposure are
< 2.3 µg/L, 2 µg/day, 0.05 µg/g wet tissue, and
0.05 µg/g wet tissue, respectively.
3
Reference val-
u
es quoted by Guys and St. Thomas’ Hospital
Toxicology Laboratory (London, UK) are < 3
nmol/L (approx. 0.32 µg/L) for blood and < 8
nmol/L (~ 0.86 µg/L) for urine.
4
Most studies on
the metabolic fate of topically applied silver have
been in patients with burns treated with SSD
cream.
5,6
In SSD cream-treated burn patients, plas-
ma concentrations may be as great as 50 µg/L
within 6 hours of treatment, dependent upon the
area that was treated, and can reach a maximum
of 310 µg/L. Silver in urine may reach a maxi-
mum of 400 µg/day. After absorption, silver has
been found in various tissues. Silver concentra-
tions in a burn patient who died of renal failure
after 8 days of treatment were 970 µg/g, 14 µg/g,
and 0.2 µg/g wet tissue in the cornea, liver, and
kidney, respectively.
3
This equates to liver con-
centration that is 280 times background. Renal
toxicity from silver has been reported after topi-
cal application, leading the authors to conclude
that topical SSD should not be used for long peri-
ods on extensive wounds.
7
Lansdown and
Williams
8
acknowledge that the use of topical sil-
ver in burns and chronic ulcers can lead to sys-
temic absorption and subsequent deposits in the
organs; however, they conclude that the risk is
low. Studies on the fate of SSD using radiolabeled
silver (Ag
110
) showed that label accumulation
occurred in superficial layers and in a short time
period after exposure (2–8 hours)—clearance was
complete in 28 days.
9
This indicates that silver
binds superficially and has low absorption from
single application. Few reported data on systemic
absorption of silver from sources other than topi-
cal SSD exist; thus, it must be assumed that under
normal conditions of use, the modern silver-con-
taining wound dressings are safe in this respect.
10
Chen et al
11
have reported increased serum and
urine silver levels and mild hepatic dysfunction
in patients with burns treated with a silver dress-
ing but concluded that it was safe on small to
medium partial-thickness burns. However, Trop
et al
12
reported silver-related hepatotoxicity and
argyria-like symptoms in a case of a silver-coated
dressing used on a child with 30% total body sur
-
face area burns. Elevated plasma and urine silver
levels of 107 µg/kg (~ 104 µg/L) and 28 µg/kg (~
27 µg /L) were measured, as were elevated liver
308 WOUNDS: A Compendium of Clinical Research and Practice
WHITE AND CUTTING
enzymes (AST, ALT, and GGT). These abnormali-
t
ies eventually resolved after cessation of silver
treatment.
The limits of exposure to silver in industrial
conditions have been reviewed and document-
ed.
1
3
Silver compounds and metal ionize, largely
to the monovalent cation Ag+; there are other
cations, but these are very reactive and short-
lived. Ag+ has a high affinity for thiol groups and
binds to reduced glutathione
14
; it also binds to the
amino-, sulphydryl, carboxyl, and phosphate
groups of nucleic acids.
15
Reduced glutathione is
important in erythrocyte function and in the elim-
ination of organic peroxides,
1
4
and any chemical
alteration to nucleic acids is likely to result in
transcription errors.
In-vitro, ex-vivo, and animal evaluation of silver
toxicity. The cytotoxicity of topically applied
agents, such as antimicrobials, has been evaluat-
ed using skin cells in vitro,
16–19
reconstituted
human epithelium (RHE),
20
and in grafted skin
substitutes.
21
The risk-benefit of cytotoxicity ver-
sus antimicrobial activity for agents applied topi-
cally to wounds has been discussed.
22
The toxicity
of silver in cells and tissues has been assessed
using silver nitrate, silver sulfadiazine, and silver
dressings. In a study on cultured human dermal
fibroblasts, silver nitrate exposure to various
quantities of fetal calf serum (resembling physio-
logical conditions) produced cytotoxic effects at
8.2 nmol/L after 8 and 24 hours.
18
In similar
experiments using monolayer cultures of 3T3
fibroblasts and keratinocytes from surgical dis-
cards, silver from silver nitrate and from a silver
dressing was found to be cytotoxic (lethal to sil-
ver nitrate at 50 x 10
-4
% after 3 hours as well as
the dressing). The same silver dressing was eval-
uated for cytotoxicity using cultured skin substi-
tutes
in vitro and in vivo after grafting.
21
Results
showed the dressing was cytotoxic in vitro within
1 day, but the in-vivo dressing was not after 1
week. These results suggest that in-vitro cytotoxi-
city is more sensitive than in vivo, as there is no
means of reducing toxicity via blood circulation,
tissue reservoir, metabolism, or by dilution
effects. It is justifiable to conclude that in-vivo or
ex-vivo studies are more likely to reflect the possi-
ble toxicity in routine clinical use.
The oligodynamic nature of silver. Bacteria in
wounds, notably chronic wounds, exist as both
p
lanktonic and sessile organisms. The latter are
attached to a surface (eg, biofilm form) that is
postulated, but not yet confirmed, as a feature of
chronic wounds.
23
Bacteria behave differently in
each of these 2 forms. This behavior becomes rel-
evant to bioburden control measures when the 2
forms exist contemporaneously in the wound.
Bacteria in planktonic form are freely available to
topical antimicrobial agents, whereas in biofilms,
bacteria are less susceptible.
24
The antimicrobial
activity of silver has been known for many years,
and numerous publications report its action
against a wide variety of organisms
in vitro.
2
5
It is
generally accepted that silver is active as the
monovalent cation Ag+ and that this species is
active at low concentrations (parts per billion
[ppb] or µg/L, to parts per million [ppm] or
mg/L) in aqueous solutions.
26
The term oligody-
namic, meaning active in small quantities, has
been used in this context in much research over
the last century.
27–31
In a review directed at SARS
(severe acute respiratory syndrome), Rentz
30
referred to the work of von Näegeli
27
who found
Ag+ to be an active biocide at concentrations
between 9.2 x 10
-
9
and 5.5 x 10
-
6
M, (ie, 9.2 ppb and
5.5 ppm). Rentz
3
0
cited a 1987 study by Cliver
3
2
that reported Ag+ was active at 250 ppb in 2
hours. The efficacy of silver ion disinfection has
been illustrated by the following calculation:
At a concentration of 10
4
cells/mL and 50 ppb
(4.7 x 10
-7
mol/L) metal ions, there are approxi-
mately 2.8 x 10
10
metal ions per cell.
25,32
This calculation represents a typical bacterial
concentration in wound exudate and a “low”
level of silver dissolution from a silver-containing
dressing. However, exudate will have an influ-
ence on silver ion activity by virtue of its anion
content (eg, Cl
-
), which bind the Ag+ ion. The
effects of protein on the binding and bioavailabil-
ity of silver ions have been investigated using an
oral bacterium, Porphyromonas gingivalis
33
; the
frequent presence of silver in the mouth from
dental amalgam
34
is known to select for resistance
and casts some doubt on the validity of these
observations.
35
According to Bechert et al,
29
“the
oligodynamic activity of silver ions is not reduced
by pre-incubation with albumin and fibrinogen.”
Currently, not much information is available that
Vol. 18, No. 11 November 2006 309
WHITE AND CUTTING
relates to the effects of silver on wound clinical
i
solates in the presence of common anions and
protein (ie, an exudate equivalent environment).
However, Bowler et al
36
addressed this situation
and challenged a silver dressing with clinical iso-
lates tested in a simulated wound fluid. Their
findings suggest that the silver-containing dress-
ing is likely to provide a barrier to infection.
The authors are unaware of any published
studies on the mutant selection window (MSW)
and mutant prevention concentration (MPC) for
silver.
37,38
The MSW has been developed using
antibiotics, so its value in antiseptic studies is a
matter for conjecture. The principles are never-
theless intriguing and further research is neces-
sary. Mutant selection window (ie, 2 concentra-
tions of antimicrobials, usually antibiotics), at the
lower level, blocks the majority of susceptible
bacteria growth. The upper limit of the window is
the concentration of antimicrobials that blocks the
growth of the least susceptible bacteria. Resis-
tance is rarely expected to develop when drug
concentrations are kept above the upper bound-
ary of the MSW. This expectation led to the upper
boundary being designated as the MPC.
The results of such studies would be highly
desirable before making assertions on the likeli-
hood of selection for resistance through the use of
dressings delivering different amounts of silver
in everyday clinical practice.
39
While claims have been made that a rapid kill
rate is essential in order to avoid resistance and
biofilm formation,
40
there is no supporting MSW
data. It is known that silver has the capacity to
disrupt the biofilm matrix at a low dose (50
ppb).
41
It could, therefore, be argued that such
claims are made more for commercial advantage
than for the advancement of clinical intervention.
Silver ions at low ppb concentrations are effec-
tive antibacterial agents against most planktonic
bacteria.
26
This level (50 ppb) has also been found
effective in destabilizing biofilms of Staphylococ-
cus epidermidis in vitro.
41
In an in-vivo study using
a biofilm-forming Staphylococcus epidermidis,
Illingworth et al
42
showed that a silver-coated
heart valve cuff exerted bactericidal activity. This
implies that the (probable) biofilm formation on
the cuff does not protect from silver ions. Thus, it
is reasonable to conclude that in the case of silver
ions, oligodynamic equates to bactericidal activi-
t
y at nanomolar (ppb) concentrations.
Dressing Association with the
Wound Bed
Sibbald
4
3
highlighted the important relation-
ship of effective wound bed preparation and the
management of wound infection through use of
antimicrobial agents. He stated that the selection
of any product should account for microbial sen-
sitivity, low allergenicity, and low cellular toxici-
ty and should not be a systemic agent. These
important considerations should not be disputed.
Irrespective of the type of antimicrobial silver
used in any medical device (eg, salts or metallic),
the form of silver delivered to the wound should
remain consistent (ie, Ag+) and not change irre-
spective of the carrier dressing. However, it is
generally recognized that silver efficacy is influ-
enced by the amount of silver and its availability,
which are dependent on the chosen product.
However, Parsons et al
44
stated that efficacy is
unrelated to the total amount of silver in the
dressing. One additional factor that impinges on
antiseptic efficacy and is not related to the form
of silver used or the dosage but should not be
overlooked is the ability of the carrier dressing to
conform to the wound bed. High conformability
helps ensure that areas of noncontact between the
dressing and the wound bed are minimized thus
reducing the formation of voids (dead space)
where bacteria may flourish. Dead space has been
identified as an impediment to successful wound
healing and efforts should be made to avoid their
occurrence.
45
A dressing that gels in contact with
wound fluid by internally binding water is more
likely to achieve high conformability with the
wound bed than one that does not conform and is
relatively inflexible. Fibrous dressings maintain
an excellent absorptive capacity yet can be
removed from the wound atraumatically while
remaining intact and retaining the additional ben-
efit of avoiding dead space formation in the
wound.
46,47
Additionally, the ability of a dressing
to maintain a high tensile strength while binding
water would seem to be advantageous.
The value of fibrous dressings in wound man-
agement has been enhanced by the silver ion
310 WOUNDS: A Compendium of Clinical Research and Practice
WHITE AND CUTTING
incorporation, resulting in an absorptive, antimi-
c
robial dressing.
48
S
uch dressings are known to
achieve and maintain intimate contact with the
wound bed—this is deemed advantageous in
wound healing because these dressings avoid cre-
ating dead space. Avoiding dead space creation
at the wound bed/dressing interface can be
demonstrated through
in-vitro methods.
49
Howev-
er, the clinical benefit obtained through the
appropriate use of such dressings is not in the
absolute bactericidal impact (ie, achieving sterili-
ty) but in the reduction of bacterial bioburden to
a level where the host immune response can
respond and regain control.
Topical antimicrobials have an important role
to play in managing wound bioburden,
50
and
product selection should take into account not
just those issues related to antimicrobial activity,
such as sensitivity, allergenicity, and cellular toxi-
city, but should consider the physical relationship
of the carrier vehicle (dressing) to the wound bed.
High conformability will help ensure the effec-
tiveness of the antimicrobial component at the
dressing/wound bed interface.
49
Not only may
the delivery of silver ions to the wound bed be
enhanced through the close proximity of the
dressing but wound bed bioburden may also be
reduced through bacterial sequestration. Walker
et al
51
demonstrated the value of sequestration in
managing bacterial pathogens using scanning
electron microscopy. Their investigations showed
that as the fibrous dressing became hydrated and
formed a cohesive gel, bacteria absorbed into the
dressing matrix were immobilized and retained
within the gel structure. This dressing property
immobilizes the bacteria and compliments the
bactericidal activity of the silver ions by reducing
the wound bed bioburden through the mecha-
nism of sequestration.
An issue related to silver and antimicrobial
efficacy that has acquired a degree of attention is
time to kill. Diametrically opposite views may be
found in the literature regarding the relevance of
time to kill in the control of wound pathogens.
40,44
A recent publication listed dressing products
with their comparative silver content
52
and
should not be interpreted as though a higher
level of silver leads to a shorter kill time or that
silver efficacy is primarily time/dose related. In a
review of silver biocides in dressings, Silver et al
53
s
tated that conclusions as to one product being
more effective than another during in-vitro tests
have little bearing on the efficacy of these prod-
ucts in human medicine. Choice of an apposite
antibacterial dressing should be based on the clin-
ical results (impact) and not on any single labora-
tory limitation.
44,53
Although the comparative tab-
ular approach is helpful (it provides a hierarchy
of silver content by product), the problem arises
that much supporting evidence is usually gener-
ated following in-vitro testing, and the clinical rel-
evance of such data requires exploration. It also
should be put into context of resistance selection
and the MSW. Some authors have published data
related to a single dressing type extolling the
apparent benefits of rapid time to kill. So this is
not viewed as an aspect of dressing performance
where products are differentiated for marketing
purposes, it must be established whether or not
time to kill due to topically applied antimicro-
bials is clinically relevant. The latter may be
applicable where such studies use type cultures
and not clinical isolates. Of equal or perhaps
greater importance is that the test model must
represent clinical use (eg, saline, serum, exudate,
dead cells).
Furthermore, the balance between antimicro-
bial dressings and systemic antibiotics also needs
to be established—when is a topical antimicrobial
dressing adequate and when should topical treat-
ment be supplemented with systemic antibiotics?
Conclusion
The appropriate use of topical silver in wound
care is not as clear-cut as some publications tend
to imply. A number of key areas still need to be
resolved. The clinical result is the ultimate test of
a silver dressing (ie, does it work in practice?). It
is likely that most silver dressings are being used
on chronic wounds as opposed to acute wounds,
such as burns. It remains to be established if data
from these 2 wound types can be reliably trans-
posed. The evidence is now clear that resistance
exists in a number of organisms.
53
The argument
over levels of silver and risks of resistance result-
ing from inadequate dosing is unresolved. It is
apparent that marketing and commercial inter-
Vol. 18, No. 11 November 2006 311
WHITE AND CUTTING
ests are clouding scientific debate. This requires
t
hat clinicians be collectively diligent in the clini-
cal use of silver dressings. There is no compelling
evidence regarding the extrapolation of in-vitro
data on bacterial activity to the in-vivo clinical sit-
uation. No data exists to support dressings
according to their silver “dosage.” Silver dress-
ings when used responsibly are of great clinical
value.
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314 WOUNDS: A Compendium of Clinical Research and Practice
WHITE AND CUTTING
... There are many studies introducing new types of silver dressings. [4,21,22] In our study, we compared sustainedrelease silver dressings with SSD dressings. ...
Article
Full-text available
Introduction: In recent times, there has been an increased use of dressings containing silver. Although there are many studies showing the impact of sustained-release silver foam dressings on microbial assay, there is a scarcity of studies on clinical and economical parameters. This study highlights the comparison between sustained-release silver dressings and 1% silver sulfadiazine (SSD) with respect to patient comfort, its impact on wound healing, and cost estimation in patients with burns.
... [12][13][14] However, concerns regarding potential cytotoxicity of silver in humans, including argyria, argyrosis, and absorption in soft tissues (brain, liver, kidney, and spleen), still exist, highlighting the importance of responsible use of silver in wound dressings. 15,16 In the work presented herein, we hypothesized that the amount of silver present in the ROCF-ciNPT skin interfacial layer is sufficient to hinder microbial growth within the dressing and it does not have significant mobility to have a localized effect on microbial colonies adjacent to or in proximal contact with the dressing. First, we investigated the ability of silver to hinder the microbial growth within the dressing over a 7-day period. ...
Article
Objective: In recent years, reticulated open-cell foam-based closed-incision negative pressure therapy (ROCF-ciNPT) has shown effectiveness in management of various postoperative incisions. These dressings consist of a skin interface layer that absorbs fluid from the skin surface and reduces the potential for microbial colonization within the dressing by means of ionic silver. This study examines the ability of silver to reduce the bioburden within the dressing as well as the localized effect due to potential silver mobility. Approach: Ability of silver to reduce bioburden within the ROCF-ciNPT dressing was assessed using Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp. Furthermore, silver mobility was assessed using an in vitro skin model to study the zone of inhibition along with released silver quantification. Using a porcine model, diffusion of silver into blood and tissue was studied using emission spectrometry and histology. Results: Microbial growth in the ROCF-ciNPT dressing was significantly reduced (∼2.7-4.9 log reduction) compared to a silver-free negative control. No zone of inhibition was observed for microbial colonies for up to 7 days with minimal localized silver release (<5.5 ppm release). In vivo studies demonstrated no measurable concentration (<0.2 μg/g) of silver in the blood, urine, feces, kidney, and liver tissue biopsy. Innovation: This study provides an important insight into silver concentration and mobility within the ROCF-ciNPT dressing, given emerging concerns associated with potential silver cytotoxicity. Conclusion: These results indicate the concentration of silver (0.019% silver by weight) in the ROCF-ciNPT dressings has been adequate to reduce bioburden within the skin interface layer, while severely limiting the amount of silver leaching out.
... There are many studies introducing new types of silver dressings. [4], [21], [22] In our study, we compared sustained-release silver dressings with SSD dressings. ...
Article
After an injury, the wounds need to be covered with a dressing. Lack of absorptive potential and sticking of dressing with the wound causes pain and slows the healing process. The aim of this study was to develop wound dressings having more absorptive potential and less sticking with the wound. The hemicelluloses from Lallemantia royleana seeds possess desirable properties for a wound dressing. The hemicellulose was blended with chitosan/chitin and glutaraldehyde to enhance the absorptive properties of the hemicellulose through cross-linking. Two types of formulations incorporating silver nanoparticles and ciprofloxacin were prepared. The composites were characterized by elemental analysis, Fourier-transform infrared spectroscopy and scanning electron microscopy, and evaluated for their antibacterial activity against E. coli (Gram-negative) and S. aureus (Gram-positive). The dressings were subjected to in vivo studies on Albino rats. The dressings were found to be porous and the silver nanoparticles and drug particles were found to be uniformly distributed in the polymeric matrix. The composite containing ciprofloxacin released the drug in a sustained manner for 14 to 16 days. From extrapolation of the data, it was discovered that the formulation would release around 80% of ciprofloxacin in about two weeks. Silver- ciprofloxacin nano-composites exhibited comparable activity (zone of inhibition 19-30 mm) against E. coli to that of ciprofloxacin (standard, 21-35mm) and relatively lower activity in case of S. aureus (zone of inhabitation 11-17 mm). The dressings did not stick to the wound site and the site remained wet during the healing process. Thus the use of hemicellulose from Lallemantia royleana seeds proved to be beneficial for preparing wound dressings with improved properties because of having high swelling index, porosity and spongy texture.
Article
Introduction: Silver ion has strong antimicrobial properties and is used in a number of wound dressings. In burn models, silver-nylon dressings produce elevated silver levels in the wound along with minimal systemic effect. We evaluated systemic toxicity in a non-burn wound model to see if a similar pattern of silver ion distribution would occur. Methods: Eight deep partial-thickness wounds each were created on the dorsum of 40 Gottingen minipigs using a Er-YAG Laser. Half were treated with a 21-day course of silver-nylon dressings (Silverlon®) and half were treated with moist gauze dressings. Wound, blood, liver and kidney silver levels, along with blood chemistry and hematology data were obtained at appropriate intervals. Results: All wounds healed well with healing enhanced by silver-nylon dressings. Silver ion was demonstrable in all wounds treated with silver-nylon at day 21 and after 14 days of no further treatment. Silver ion was not detected in blood, liver or kidney of any animal treated with silver-nylon or control dressings. Liver and kidney function remained normal in all animals. Conclusion: A 21-day application of silver-nylon dressings to a non-burn dermal wound produces no systemic or local toxicity in Gottingen minipigs.
Article
A green method using Juglans regia bark extract was employed to synthesize silver nanoparticles at room temperature with monitoring by absorption spectroscopy. The size and shape of the synthesized nanoparticles were characterized by infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, high resolution transmission electron microscopy, and small-angle X-ray scattering. The average particle size was from 10 to 30 nm. Gas chromatography - mass spectrometry (GC-MS) was employed for the separation, identification, and quantification of the components of the plant extracts. A possible mechanism for the synthesis of nanoparticles was elucidated based on the GC-MS results. The synthesized silver nanoparticles showed effective inhibition against Streptococcus mutans, which is the main causative agent for dental caries. The nanoparticles also showed promising anti-biofilm activity by inhibiting the glucosyltransferase enzyme.
Article
Unlabelled: Purpose. Silver wound dressings are widely used in the treatment of burns. Dressings differ in material characteristics, various antimicrobial activities, and ease of use. The purpose of this study was to evaluate both dressing performance and amount of pain during the dressing changes of 2 silver dressings Urgotul SSD® (Laboratoires Urgo, Chenove, France), and Contreet Ag® (Coloplast, Minneapolis, MN) in children. Methods: A retrospective cohort study was performed with 2 groups of 20 burns treated with Urgotul SSD and Contreet Ag until the wounds were healed or grafted. Seventy dressing changes in the Contreet Ag group and 67 dressing changes in the Urgotul group were evaluated. Every dressing change was assessed regarding the dressing performance (exudate, adherence, bleeding, and dressing application/removal), and pain. Results: Pain was "absent or slight" in 61 (92%) dressing changes with Urgotul SSD, and in 60 (85%) of the dressing changes with Contreet Ag. Dressing application in the Urgotul group was more often "very easy" (n = 33; 49%) or "easy" (n = 32; 48%) than in the Contreet Ag group, "very easy" (n = 25; 35%), and "easy" (n = 42; 60%). Contreet Ag had a greater ability to absorb exudate ("very good" n = 60; 85%, and "good" n = 11; 15%) than Urgotul SSD ("very good" n = 34; 51%, and "good" n = 13; 19%). Conclusion: Urgotul SSD and Contreet Ag are comparable regarding pain during dressing change. The dressings differ in their ability to absorb exudate and ease of application. Both dressings provided nearly painless wound management, and therefore were highly accepted by the nurses and especially the children being treated.
Article
Full-text available
The chronic wounds represent a public health problem health which the prevalence increases with age, patient health and sedentary lifestyle. Indeed, in the occidental countries, 1.69% of the elderly person aged over 65 years is suffering from leg ulcers . Moreover, the chronic wounds appearance increases for the diabetic patients who suffering neuropathy (diabetic type I and II together) with 2.2%/years of probability to developp a leg ulcer. The infection of the chronic wounds increases with wound healing delay, thus, cares need to be repeated to prevent or fight wound infection until their complete healing. In the case of infected wound, the critical colonization or localized infection can result without adapted treatment to surgery operation in order to prevent systemic infection or death. Nevertheless, the chronic wound represents a favourable site for the rapid developpment of the pathogen agents. The bacterial proliferation can lead to the biofilm formation which increases the bacterial protection against the body\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s natural defences and antimicrobial agents. So, the aim of this work is elaborate a medical device as wound dressing for extended broad spectrum antibacterial drug release. The textile device used in this project is a non-woven textile based on polyethylene terephtalate (PET) functionalized with Pad-Dry-Cure method with chitosan (CHT). In the present work, two crosslinking agents are evaluated, genipin (Gpn) and citric acid (CTR), which allows obtaining a CHT network coated at the surface of the textile fibers. Thus, there are ionic functions at the surface of the PET; positive charges when the crosslink agent is Gpn, positive or negative charges in function of the amount of the CTR used in the solution.The ionic charges from the PET functionalized by CHT crosslinked by Gpn (PET-Gpn/CHT), are used to build a multilayer system layer-by layer self-assembly. The polyelectrolytes (PE) used to build this multilayer system by dip-coating are: the CHT, as cationic PE, and cyclodextrin (CD) polymer, as anionic PE (it was developed and studied by the team in previously work). The ability of the CD to form inclusion complex, from the CD polymer included in the multilayer coating, is used in the case of PET-Gpn/CHT to load one antiseptic with broad spectrum, the chlorhexidine (Chx). This Chx loaded multilayer system is optimized and evaluated physic-chemically, biologically and microbiologically. The study is also realized on the functionalized PET-CTR/CHT. This system, anionic or cationic, in function of the quantity of the crosslinking agent used, is loaded respectively by silver (Ag+) or iodide (I3-). A physico-chemical and microbiological evaluation are realized to evaluate their antibacterial efficiency. Finally, the multilayer system is built-up on the anionic PET-CTR/CHT loaded by silver to reduce its release out of the multilayer system. Chemical completed by microbiology tests are realized to verify the influence on the antibacterial activity and the kinetic of the release of the multilayer system
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Fungal infections can attack epithelial tissues and, according to the immunological state of the patient, some of them invade deeper organs, becoming seriously life compromising. Besides, bloodstream and local infections associated with intravascular devices constitute a significant problem associated with increased mortality. Topical therapy is desirable since, in addition to targeting the site of infection, it reduces the risk of systemic side effects and increases patient compliance. In this review we describe the pros and cons of using nano-objects that being toxic in nature could be used to cover surfaces of medical devices, or can act as carriers for targeted delivery of antifungals to skin. Non-toxic nano-objects were also included because they improve the ocular delivery of antifungals, classically suffering from ineffective topical administration, difficult access for systemic medication or local invasive administration. The new preclinical developments of nanoparticulate agents against cutaneous and ocular mycosis are grouped in three main sections: (1) In vitro antifungal activity of metallic nanoparticles, (2) In vitro and in vivo antifungal activity of non metallic nanoparticles (3) Ocular delivery of non metallic nanoparticles.
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Recently, a hydrofiber dressing (Aquacel®, Convatec, a Bristol-Myers Squibb Co., Deeside, United Kingdom) has been used successfully for the treatment of partial-thickness burns. The hydrofiber dressings were not changed daily but left on the wounds for prolonged periods. After the new epidermis was closed, the dressings could be easily removed. To obtain more insight in the behavior of inflammatory cells in these wounds treated with the hydrofiber dressing, the authors prepared partial-thickness wounds in rats. The effects of the hydrofiber dressing were compared to that of a paraffin-impregnated gauze dressing (Jelonet™, Smith & Nephew, United Kingdom). The hydrofiber dressing adhered to the wounds by fibrin and fibronectin, leaving no dead space between the dressing and the wound bed. On the paraffin-impregnated gauze-covered wounds a crust was formed and sometimes the gauze became incorporated, leading to further damage upon dressing removal. A remarkable feature of the hydrofiber dressing was its capability to absorb and capture cells into the dressing. The uptake took place the first three days after wounding, and the cells were mainly neutrophils. This resulted in significantly lower numbers of these cells in the wound bed when compared to the paraffin-impregnated gauze-covered wounds. Reepithelization was significantly faster in wounds covered with the hydrofiber dressing. Presumably, the lower numbers of neutrophils in the wound bed contribute to a better environment for the outgrowth of keratinocytes. However, the authors' results indicate that the demands on the secondary dressing used to cover the hydrofiber dressing are more critical compared to paraffin-impregnated gauze. The secondary dressing must be nonocclusive to allow normal differentiation of the keratinocytes.
Article
Full-text available
Silver-containing dressings are widely used to assist with management of infected wounds and those at risk of infection. However, such dressings have varied responses in clinical use due to technological differences in the nature of their silver content and release and in properties of the dressings themselves. This study examines the relationship between silver content, rate of silver release, and antibacterial activity in a simulated wound fluid model against Staphylococcus aureus and Pseudomonas aeruginosa. The study also looks at other important measures for the clinical performance of dressings including fluid handling properties and dressing pH. Seven proprietary silver-containing dressings AQUACEL® Ag [Hydrofiber®; "nonwoven A"], Acticoat Absorbent [alginate; "nonwoven B"], SILVERCEL'" [alginate-carboxymethylcellulose nylon blended fibers; "nonwoven C”], Contreet' Foam [nonadhesive; "foam A"], PolyMem ® Silver ["foam B"], Urgotul® S.Ag ["gauze"] and SilvaSorb® ["hydrogel"]) were assessed. No direct correlation between silver content, silver release, and antibacterial activity was found. Dressings with the highest silver content were nonwoven B and nonwoven C, while the lowest levels were found in nonwoven A and hydrogel. Nonwoven A, gauze, and nonwoven B were most effective against S. aureus and P.aeruginosa; however, their silver release rates differed widely. Free fluid absorption was greatest for the 2 foam dressings and least for gauze. However, nonwoven A and nonwoven B showed the best fluid retention under conditions of compression, while nonwoven A demonstrated the lowest level of capillary wicking. Dressing choice is a vital part of the successful management of infected wounds and those wounds at risk for infection. This study suggests that dressing selection should be based on the overall properties of the dressing clinically relevant to the wound type and condition.
Article
Silver sulfadiazine cream (SSD) has been used successfully in the management of burn wound sepsis. Silver deposition has been found in the skin, gingiva, cornea, liver, and kidney of patients treated with this cream, causing argyria, ocular injury, leukopenia, and toxicity in kidney, liver, and neurologic tissues. Monitoring concentrations of silver in blood and urine of patients receiving this treatment has become necessary, but sensitive and suitable methods adaptable to a clinical laboratory are still needed. We have developed a flameless thermal atomic absorption spectrophotometric method to measure silver concentrations in blood, urine, and other tissues. The detection limit is 0.4 microgram/L; the within-run precisions (CV) are 5.16%, 3.83%, and 2.79% for concentrations of 5, 13.5, and 42 micrograms/L, respectively; and the between-run precisions are 4.3% and 3.2% for concentrations of 13.5 and 42 micrograms/L. The concentrations of silver in blood, urine, liver, and kidney of subjects without industrial or medicinal exposure are less than 2.3 micrograms/L, 2 micrograms/day, 0.05 microgram/g wet tissue, and 0.05 microgram/g wet tissue, respectively. In SSD cream-treated burn patients, plasma concentrations may be as great as 50 micrograms/L within 6 h of treatment and can reach a maximum of 310 micrograms/L. Silver in urine is detectable after one day of treatment and may reach a maximum of 400 micrograms/day. After absorption, silver was found to be deposited in various tissues. Tissue silver concentrations in one burn patient who died of renal failure after eight days of treatment were 970, 14, and 0.2 micrograms/g wet tissue in cornea, liver, and kidney, respectively.
Article
The spread of antibiotic-resistant strains of micro-organisms such as methicillin-resistant Staphylococcus aureus (MRSA) represents an ever-increasing threat to the health of vulnerable people throughout the world who are obliged to spend extended periods in healthcare facilities. The organism is also responsible for increasing the financial burden placed on such centres and the wider community at large, with the result that precious financial resources are diverted from other areas of need to deal with the consequences of infection. There is general agreement that the problem of resistance has been exacerbated by the overuse or misuse of antibiotics so, wherever possible, alternative methods are now required to manage topical infections caused by antibiotic-resistant organisms. Open wounds act as an important focus for cross-infection, necessitating the application of appropriate measures to eliminate or prevent the spread of bacteria from such lesions. Some topical products that can be used in the treatment of wound infections are described, with particular emphasis on the potential value of silver-containing dressings.
Article
The ability of a dressing to conform to the contours of a wound is important to reduce areas of noncontact where bacteria may proliferate. For antimicrobial dressings, such as those containing silver or iodine, a high degree of conformability to uneven wound surfaces may be particularly important to ensure effectiveness of the antimicrobial dressing at the wound-dressing interface. These in-vitro studies investigated conformability of 2 silver-containing wound dressings, a nanocrystalline silver-containing (NSC) dressing (Acticoat™, Smith & Nephew, London, UK) and a silver-containing Hydrofiber® (SCH) dressing (AQUACEL® Ag, ConvaTec, Skillman, NJ, USA), to human wound tissue and dried dermal membrane (simulated dry eschar) and also to the surface of indented agar plates inoculated with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. The SCH dressing provided excellent conformability to dermal tissue and is likely to expose all aspects of the uneven surface to the antimicrobial action of ionic silver provided in the dressing. Conformability of the NSC dressing was less evident; small areas of noncontact were clearly visible. Conformability assays on agar plates demonstrated that the SCH dressing was more effective than the NSC dressing at killing bacteria on an indented surface. Image analysis showed that for water-moistened dressings on plates inoculated with MRSA, 94.86% of the area under the SCH dressing was clear of bacterial growth at study conclusion, compared to only 6.25% of the area under the NSC dressing (control: 0%). Similar results were seen for P. aeruginosa, regardless of whether dressings were hydrated with saline or water. These findings may have clinical implications, especially for the care of wounds with uneven contours.
Article
Biofilms consist of bacteria and other organisms that live within a matrix of extracellular polysaccharide (EPS) and have been implicated in bacterial diseases, such as otitis media, dental plaque, and chronic infections in cystic fibrosis. The purpose of this study was to examine wounds for the formation of bacterial biofilms. Partial-thickness wounds were made on three pigs with a dermatome. Wounds were challenged with Pseudomonas aeruginosa and covered with either a polyurethane dressing or plastic cover slip. At 72 hours, each wound was vigorously flushed three times with sterile saline to dislodge any non-adherent bacteria. The flushed wounds were then cultured with a surfactant solution using a scrub technique. Both the flushed and scrubbed samples were plated on Pseudomonas isolation agar for quantitation. Cover slips were removed from the wounds at 72 hours, and wound curettage was obtained. Congo red staining procedure, which detects EPS, was used to stain both cultures. A thick, dark red to yellow-orange amorphous EPS matrix was seen surrounding bacteria, indicating a biofilm. Wounds cultured with saline or surfactant demonstrated that there were two distinct populations of bacteria living in the wound area. The non-adherent population displayed a quantitative variation from wound to wound, whereas the adherent population had a narrower range suggesting a critical mass for those bacteria that were adherent to the wound. This preliminary work has demonstrated that bacterial biofilms do form in wounds. This in-vivo assay system will provide a means to examine therapeutic modalities for bacteria living in a protective biofilm.
Article
Disinfection due to copper or silver ions may result from action at the cell or capsid protein surface or on the nucleic acid of cells or viruses. Metals may alter enzyme structure and function or facilitate hydrolysis or nucleophilic displacement. The means by which cells may reduce the toxic effect of metal ions include: biomethylation, complexation with metallothionen, development of efflux pumps, the binding of metal ions to cell surfaces, and the removal of metal ions by precipitation. The phenomenon of “multiplicity of reactivation” may reduce the effect of a disinfectant on a virus by allowing a clump of partially inactivated viruses to produce a productive infection in a susceptible cell. Conditions which may affect metal ion‐biomolecule interaction include: pH, ionic strength, temperature, dissolved oxygen, presence of interfering substances or light, the chemical form and valency of the metal ion, and the condition of the microorganisms.
Article
IntroductionProlonged topical application of silver sulfadiazine cream can induce argyria and adverse effects of sulphonamides. We report a case of a woman with acute renal failure following repeated applications of topical silver sulfadiazine on pyoderma gangrenosum wounds.Case reportA 61 year-old woman suffering from rheumatoid arthritis, Sjogren's syndrome and scleroderma was treated with corticosteroids (1 mg/kg/day) and topical application of silver sulfadiazine cream (200 g/day) for extensive pyoderma gangrenosum wounds on the legs. Three weeks later, the patient was transferred to intensive care because of pulmonary edema, oligoanuria and disrupted consciousness. Laboratory data revealed leukopenia (1100/mm3) with neutropenia and renal failure (serum creatinine 316 μmol/l). Proteinuria was moderate and ultrasonography of the kidneys was normal. Silver concentration in blood was 1818 nmol/l (N < 92 nmol/l) and 1381 nmol/l (N < 9 nmol/l) in urine. Sulfadiazine concentration in blood was undetectable. All the signs regressed after withdrawal of silver sulfadiazine and after several sessions of hemodialysis.DiscussionVarious causes of renal failure are discussed in our patient. However, direct silver-induced renal toxicity is the most likely and is confirmed by the high concentration of silver in blood and urine and the improvement on withdrawal of the topical cream, without modification in the oral treatment. The absence of red corpuscles and crystals in the urine and undetectable concentrations of sulfadiazine in blood are not in favor of sulphonamide renal toxicity. Furthermore, the autoimmune diseases of our patient were well-controlled. Leukopenia could be secondary to silver sulfadiazine medullar toxicity. This observation confirms that this topical cream should not be used for long periods on extensive wounds.
Article
The attachment of Ag110-labeled sulfadiazine silver (AgSU) to the burn wound of humans and full and partial thickness scald burns of rats was studied over time. The duration of Ag adherence to burned skin and the absorption and organ distribution of ingested AgSU was studied. Peak attachment to human burns was 1% of the administered dose in 24 hours. Rat wounds showed greater attachment. Dissections of the wounds showed 81% to 98.7% of this attachment to be in the most superficial layers of cells and no silver was observed in organs of surface-treated animals. Duration of attachment after one application was until wound slough with percent attachment dropping from 5% to 1.7% over that time. Oral ingestion resulted in substantial silver deposition, particularly in liver and lungs. Clearance occurs in three weeks. The basic function of AgSU may be through the slow release of silver into the superficial wound environment.