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Silver
in
medicine:
A
brief
history
BC
335
to
present
§
David
J.
Barillo
a,
*,
David
E.
Marx
b
a
Disaster
Response/Critical
Care
Consultants,
LLC,
Mount
Pleasant,
SC,
USA
b
Department
of
Chemistry,
University
of
Scranton,
Scranton,
PA,
USA
1.
Introduction
Silver
is
a
naturally
occurring
element
that
has
been
used
for
millennia
for
currency
and
jewelry;
for
food
serving;
for
water
purification;
and,
more
recently,
for
electrical
and
industrial
applications.
Ionized
silver
(Ag
+1
)
has
known
antimicrobial
properties
and
has
been
employed
in
burn
wound
care
for
over
200
years.
More
recently,
the
health-promoting
properties
of
silver
have
been
touted
in
a
number
of
consumer
products,
including
silver-containing
clothing,
refrigerators,
and
wash-
ing
machines
that
claim
to
deodorize
or
sanitize
by
‘killing
germs’.
Several
new
wound
dressings
and
gels
containing
silver
ion
or
silver
compounds
are
currently
being
marketed.
The
rediscovery
of
silver
for
medicinal
uses
has
prompted
exaggerated
claims
by
both
proponents
and
detractors
of
silver
therapy.
The
Internet,
which
was
not
available
during
the
last
wave
of
silver
popularity
in
the
1960s,
has
only
added
to
the
confusion.
Oral
colloidal
silver
solutions,
although
outlawed
by
the
US
Food
and
Drug
Administration,
are
still
advocated,
advertised
and
available
over
the
Internet.
Claims
are
made
that
the
consumption
of
colloidal
silver
can
treat
or
cure
650
different
diseases
or
disease
organisms
including
HIV,
cancer,
tuberculosis,
malaria,
lupus,
syphilis,
typhus,
tetanus,
bubonic
plague,
cholera,
warts,
Menieres
Disease,
hemorrhoids,
ringworm,
prostatism,
acne,
sinusitis,
appendi-
citis,
anthrax,
Hanta,
Ebola,
and
flesh-eating
bacteria
[1–4].
The
lack
of
data
supporting
these
claims
is
matched
by
equally
unscientific
concerns
raised
by
detractors
of
silver
therapy.
The
widespread
adoption
of
new
silver
dressings,
in
their
view,
will
cause
skin
to
turn
blue,
result
in
universal
cross-
species
resistance
of
bacteria
to
all
known
antibiotics,
and
irrevocably
destroy
ecosystems.
The
truth
obviously
belongs
somewhere
in
between
these
two
extremes,
and
common
sense
has
been
sorely
lacking.
Silver
is
not
a
new
product
or
laboratory-manufactured
b
u
r
n
s
4
0
s
(
2
0
1
4
)
s
3
–
s
8
a
r
t
i
c
l
e
i
n
f
o
Keywords:
Silver
Antimicrobial
Burn
Wound
healing
Acute
wound
Chronic
wound
a
b
s
t
r
a
c
t
Silver
is
a
naturally
occurring
element.
Similar
to
other
metals,
the
ionized
form
of
silver
(Ag
+1
)
has
known
antimicrobial
properties.
A
number
of
wound
dressings
incorporating
silver
ion
or
silver
compounds
have
recently
been
developed
and
marketed.
In
addition,
the
antimicrobial
effects
of
silver
are
currently
being
promoted
in
consumer
products
such
as
clothing
and
household
appliances.
The
present
use
of
silver
in
medical
and
consumer
products
has
prompted
concerns
for
potential
toxicity
and
ecological
effects,
including
induction
of
microbial
resistance
to
antibiotics.
These
concerns
ignore
the
fact
that
silver
has
been
used
for
medicinal
purposes
for
several
thousand
years.
A
historical
review
of
the
uses
of
silver
in
medicine
is
presented.
#
2014
Elsevier
Ltd
and
ISBI.
All
rights
reserved.
§
Presented
at
a
symposium
on
‘‘Silver
in
Medicine:
Customs
and
Controversies’’
held
in
Association
with
the
24th
Annual
Southern
Region
Burn
Conference,
Winston-Salem,
NC,
December
2,
2011.
*
Corresponding
author
at:
Disaster
Response/Critical
Care
Consultants,
LLC,
PO
Box
683,
Mount
Pleasant,
SC
29465,
USA.
E-mail
address:
dbarillo@gmail.com
(D.J.
Barillo).
Available
online
at
www.sciencedirect.com
ScienceDirect
journal
homepage:
www.elsevier.com/locate/burns
http://dx.doi.org/10.1016/j.burns.2014.09.009
0305-4179/#
2014
Elsevier
Ltd
and
ISBI.
All
rights
reserved.
superdisinfectant.
People
have
used
silver
in
various
forms
for
at
least
5000
years,
including
jewelry
and
body
piercing.
There
is
evidence
that
humans
learned
to
separate
silver
from
other
metals
as
early
as
3000
BC
[5].
The
use
of
silver
for
currency
and
food
handling
(drinking
cups)
is
mentioned
in
the
first
book
of
the
Old
Testament
(Genesis
Chapters
13:2,
20:16,
23:15,
24:35,
24:53,
33:19,
37:28,
42:25,
42:27,
and
44:2)
[5,6].
While
manufacturers
of
silver
dressings
claim
the
medical
applica-
tions
of
silver
as
a
new
idea,
in
truth,
silver
has
been
used
for
medicinal
purposes
for
thousands
of
years.
In
this
article,
the
history
of
the
medicinal
uses
of
silver
is
reviewed.
2.
Review
From
the
authors
standpoint,
the
history
of
silver
in
medicine
may
be
conveniently
divided
into
the
eras
of
ancient
history;
the
1800s
and
Germ
Theory
of
disease;
the
silver
renaissance
of
the
1960s;
the
second
generation
of
silver
dressings
in
the
late
20th
century;
and
current
uses.
Prior
to
the
establishment
of
the
Germ
Theory
of
disease,
the
use
of
silver
for
medicinal
purposes
was
based
on
folklore
or
tradition.
Probably
the
earliest
medical
use
of
silver
was
for
water
disinfection
and
storage
[7].
Alexander
the
Great
(335
BC)
stored
and
drank
water
in
silver
vessels
when
going
on
campaigns
[7–10].
The
Greeks
and
Romans
also
stored
water
in
silver
vessels
to
keep
it
fresh.
Ancient
Mediterranean
and
Asiatic
cultures
used
silver
flasks
and
storage
containers
to
prevent
spoilage
of
liquids,
and
placed
silver
foil
into
wounds
to
prevent
infection
[11].
The
Romans
included
silver
in
their
official
book
of
medicines
and
were
known
to
have
used
silver
nitrate
[8].
Ambrose
Pare
(1510–1590)
was
a
pioneer
of
battlefield
surgery
and
served
as
royal
surgeon
to
Kings
Henry
II,
Francis
II,
Charles
IX
and
Henry
III.
Among
other
innova-
tions,
he
championed
the
use
of
silver
clips
for
facial
reconstruction
[12].
The
Germ
Theory
of
disease
postulated
that
microorgan-
isms
were
responsible
for
certain
diseases.
Evidence
to
support
this
theory
came
from
Semmelweis
in
1847
(hand
washing),
John
Snow
in
1854
(epidemiology
of
a
cholera
outbreak),
Davaine
in
1865
(identification
of
anthrax
bacteria
in
blood),
Louis
Pasteur
in
1880
(isolation
and
culture
of
chicken
cholera
bacteria),
Robert
Koch
in
1876
(isolation
of
Bacillus
anthracis
and
Koch’s
Postulates;
and
others
[13].
The
idea
that
microbes
could
cause
disease
and
the
fact
that
silver
ion
had
strong
antimicrobial
properties
provided
a
rational
basis
for
the
medicinal
uses
of
silver
that
were
already
in
place.
On
the
other
side
of
the
ocean,
silver
was
finding
niche
medical
applications.
Americans
traveling
west
during
the
1880s
placed
silver
coins
in
water
barrels
because
this
practice
was
known
to
retard
the
growth
of
bacteria
and
algae
[14,15].
Perhaps
the
most
unique
application,
however,
was
the
use
of
a
silver
plate
for
a
cranioplasty
performed
by
Dr
Georgia
Arbuckle
Fix
[16].
Dr.
Fix
was
the
only
women
in
the
founding
class
of
eight
students
at
the
College
of
Medicine
of
Omaha
in
1881
[17].
Following
graduation,
she
started
a
practice
in
western
Nebraska
in
1886,
where
she
was
the
only
physician
for
a
75-mile
radius
[17].
In
1890,
she
was
called
to
attend
on
a
man
with
an
open
skull
injury
resulting
from
a
farming
accident
[16].
She
successfully
closed
the
skull
defect
with
a
plate
created
from
a
silver
coin,
which,
according
to
legend,
she
hammered
into
a
thin
sheet
using
a
fencing
hammer
and
piece
of
rail
iron.
In
the
1880s,
the
German
obstetrician
Karl
Crede
found
that
dilute
solutions
of
silver
nitrate
reduced
the
incidence
of
neonatal
eye
infections
from
10.8%
to
under
2%
[12].
The
application
of
silver
nitrate
solution
to
the
eyes
of
newborns
to
prevent
ophthalmia
neonatorium
became
mandatory
by
state
law
in
most
United
States
jurisdictions
by
the
early
1900s.
In
the
late
1970s
both
the
US
Centers
for
Disease
Control
(CDC)
and
the
American
Academy
of
Pediatrics
still
advocated
silver
nitrate
as
one
of
three
antibiotic
choices
(erythromycin,
tetracycline
or
silver
nitrate)
for
this
indication.
Erythromycin
0.5%
ointment
is
now
the
only
regimen
recommended
by
CDC,
as
the
other
two
eye
preparations
are
no
longer
available
[18].
William
Halstead,
MD
became
the
first
Chief
of
Surgery
at
the
Johns
Hopkins
Hospital
in
1889.
In
this
capacity,
he
established
the
first
surgical
residency
program
in
the
United
States.
Halstead
advanced
the
field
of
wound
healing,
and
was
an
advocate
of
careful
hemostasis,
aseptic
technique,
meticu-
lous
anatomic
dissection
and
tension-free
closure.
Among
his
other
surgical
innovations,
Halstead
employed
silver
wire
suture
for
hernia
repair
and
found
silver
foil
an
effective
means
of
controlling
postoperative
wound
infections
[12,19].
Silver
in
its
numerous
forms
has
been
used
for
over
200
years
in
the
treatment
of
burn
injury
[15,20]
and
silver
nitrate
solutions
in
5%
and
10%
concentrations
were
used
as
caustics
or
escharotics
in
the
early
20th
century
[21].
The
true
renaissance
of
silver
in
medicine,
however,
occurred
in
the
1960s,
when
silver
compounds
revolutionized
burn
wound
care
and
then
found
application
in
manned
space
flight.
In
1964,
the
value
of
mafenide
acetate
(Sulfamylon
1
)
as
a
topical
burn
treatment
was
established
in
human
clinical
trials
[21].
In
the
following
year
Moyer
et
al.
pioneered
the
use
of
0.5%
silver
nitrate
solution
as
a
topical
therapy
for
burn
patients
[21,22].
His
work
was
influenced
by
the
experiences
of
one
of
his
co-authors,
who
had
been
using
topical
silver
nitrate
solutions
as
an
adjunct
for
the
management
of
necrotizing
fasciitis
since
1941
[21,22].
The
original
article
described
a
dressing
methodology,
and
included
a
recommendation
that
burn
units
be
constructed
of
black
floors
and
walls
because
of
the
dark
staining
that
the
use
of
silver
nitrate
produced
[21,22].
In
the
initial
7
months
of
use,
there
was
no
new
emergence
of
bacterial
resistance
noted
in
over
1300
wound
cultures
[21,22].
With
the
successes
of
sulfamylon
and
silver
nitrate
demonstrated,
the
next
logical
step
was
a
combination
of
the
two
drug
classes.
Dr.
Charles
Fox,
working
at
Columbia
University
in
New
York
had
previously
studied
soluble
sulfonamides
for
burn
wound
care.
He
mixed
silver
nitrate
with
a
weakly
acidic
sulfadiazine
to
create
silver-sulfadiazene
[21].
His
initial
report
on
silver
sulfadiazine,
published
in
1968
described
success
in
a
mouse
model
followed
by
ongoing
human
studies
[23].
The
mouse
model
utilized
a
scald
burn
seeded
with
Pseudomonas
aeruginosa
and
had
an
expected
mortality
of
over
80%.
The
once-daily
application
of
silver
sulfadiazine
decreased
mortality
to
‘between
5%
and
20%
in
8
days
or
longer
in
numerous
experiments
involving
approxi-
mately
1280
mice’
[23].
Silver-sulfadiazene
was
also
applied
to
b
u
r
n
s
4
0
s
(
2
0
1
4
)
s
3
–
s
8S4
16
human
patients
with
burns
between
20%
and
85%
body
surface
area
as
part
of
an
ongoing
study
[23],
however,
detailed
results
were
not
reported.
A
second
paper
by
describing
use
of
silver
sulfadiazine
on
24
burn
patients
treated
in
New
York
City
and
33
patients
treated
at
the
Can
Tho
Provincial
Hospital,
Republic
of
Vietnam
was
published
in
1969
[24].
Fox
and
Modak
further
investigated
the
mechanism
of
action
of
silver-
sulfadiazene
and
found
that
silver,
but
not
sulfadiazine
was
bound
by
bacteria
[25].
They
postulated
that
the
combination
of
both
drugs,
in
the
presence
of
serum
and
sodium
containing
body
fluids,
allowed
slow
and
sustained
release
of
silver
ion
[25].
Silver
sulfadiazine
is
sparingly
soluble
in
water
but
readily
ionizes
in
body
fluids
to
release
ionic
silver.
In
addition
to
silver,
rare-earth
elements
are
also
known
to
have
antimicrobial
activity
in
vitro
[26].
In
1977,
Fox
and
colleagues
evaluated
the
combination
of
cerium
salts
added
to
silver
sulfadiazine
and
found
better
suppression
of
wound
bacterial
growth
[26].
This
was
later
developed
commercially
as
Flammacerium
1
,
a
combination
of
1%
silver
sulfadiazene
and
2.2%
cerium
nitrate.
In
addition
to
antimicrobial
effect,
the
cerium
ion
is
claimed
to
reduce
inflammatory
changes
and
reduce
mortality
[12,27].
Flammacerium
1
is
widely
used
in
Europe
but
is
not
approved
by
the
U.S
Food
and
Drug
Administration
for
use
in
the
United
States.
Despite
the
availability
of
newer
topical
antimicrobials,
both
0.5%
silver
nitrate
solution
and
1%
silver
sulfadiazine
cream
continue
to
be
used
in
contemporary
burn
care
[21].
Silver
nitrate
at
0.5%
is
highly
effective
against
P.
aeruginosa
and
may
to
be
superior
to
chlorhedixine
against
more
resistant
strains
of
Streptococcus
pyogenes
and
Staphylococcus
aureus
[12].
At
the
same
time
that
silver
nitrate
and
silver
sulfadiazine
were
being
developed
for
burn
care,
the
National
Aeronautics
and
Space
Administration
was
studying
the
use
of
silver
for
extra-terrestrial
applications
[28,29].
In
the
midst
of
the
Cold
War,
the
launch
of
the
Soviet
satellite
Sputnik
in
October,
1957
started
a
race
between
the
Soviet
Union
and
the
United
States
to
land
humans
on
the
moon.
The
technologic
challenges
involved
included
life-support
systems
for
astronauts
living
for
extended
periods
in
space.
Water
is
the
most
critical
life-
support
element
aboard
spacecraft
[30].
Birmele
et
al.
note
that
the
per-capita
water
requirements
(4.5
L/day
as
either
liquid
or
water
in
food)
represents
twice
the
mass
required
for
food
and
oxygen
combined
[30].
Bacterial
contamination
of
drinking
water
would
pose
a
serious
health
risk,
and
one
can
imagine
the
problems
of
gastroenteritis,
diarrhea
and
vomiting
in
a
zero-gravity
environment.
The
original
United
States
space
program
consisted
of
Mercury,
Gemini
and
Apollo
missions.
Mercury
missions
(1959–1963)
were
a
series
of
six
manned
flights
of
15
min–34
h
duration,
each
carrying
one
astronaut.
The
water
supply
consisted
of
one
bladder
filled
with
tap
water
before
launch.
The
purity
of
the
water
depended
on
the
chlorine
added
to
the
public
water
system
in
Cocoa
Beach,
Florida,
where
the
flights
originated
[31].
The
Gemini
program
(1965–1966)
had
10
manned
flights,
each
carrying
two
astronauts
in
low
earth
orbit
for
durations
of
5
h
to
14
days.
Gemini
spacecraft
carried
7.3
liter
water
bladders,
with
chlorine
added
prior
to
launch
[31].
The
Apollo
program
(1966–1972)
consisted
of
11
manned
missions
that
included
six
moon
landings.
Because
Apollo
spacecraft
were
designed
to
carry
three
astronauts
for
long
missions,
water
requirements
were
higher.
A
NASA-funded
study
in
the
mid
1960s
investigated
the
use
of
silver
for
control
of
microbial
contamination
in
water
supply
subsystems
and
concluded
that
a
silver-ion
concentration
of
50
parts-per-
billion
was
sufficient
for
water
disinfection
[28].
A
simple
electrode
device
was
designed
to
pass
a
weak
direct
current
thru
a
silver
anode
to
add
ionic
silver
to
water
[28],
followed
by
development
of
a
self-contained
flight-rated
water
steriliza-
tion
cell
measuring
2.5
4
inches
and
weighing
0.6
pounds,
including
the
battery
[29].
The
final
Apollo
spacecraft
design
consisted
of
three
separate
modules
(service,
command
and
lunar-landing)
and
used
combinations
of
chlorine,
iodine
and
ionic
silver
to
purify
water
in
different
subsystems
[7,31].
Soviet
spacecraft
also
utilized
silver
for
water
purification.
The
Vostok,
Voskhod
and
Soyuz
series
of
spacecraft
added
a
silver
preparation
to
the
(boiled)
drinking
water
supply
before
launch
[31].
The
Salyut
and
Mir
spacecraft
used
ionic
silver
at
0.2
mg/L
to
purify
water
[31].
Ionic
silver
was
also
used
for
purifying
and
storing
water
on
the
US
Space
Shuttle
fleet,
and
is
currently
used
on
the
International
Space
Station
[31].
NASA
has
licensed
their
water
purification
metal
ion
technology
for
commercial
development,
and
water
filters
based
on
silver-ion,
copper-ion
or
combined
technologies
are
now
used
to
disinfect
water
in
swimming
pools,
spas,
decorative
fountains,
and
animal
habitats
for
dolphins,
sea
lions
and
sea
turtles.
Copper/silver
filters
are
also
used
in
hospital
water
supplies
to
prevent
Legionella
infection
[12,32].
The
last
two
decades
of
the
20th
century
saw
the
development
of
silver-based
textiles
for
burn
and
wound
dressings.
A
number
of
centers
investigated
the
antimicrobial
properties
of
silver-coated
nylon,
a
fabric
which
was
originally
developed
as
a
flexible
electrical
shield
or
radar
reflector
[33,34].
Deitch
et
al.
examined
the
antimicrobial
properties
of
silver-nylon
in
vitro
and
showed
effectiveness
against
P.
aeruginosa,
S.
aureus
and
Candida
albicans
[33].
Spadaro
et
al.
demonstrated
that
weak
electric
current
delivered
thru
silver
electrodes
was
‘extremely
bacteriostatic’
against
agar
plate
bacterial
cultures
of
S.
aureus,
Escherichia
coli,
Proteus
vulgaris
and
P.
Aeruginosa
[35].
The
US
Army
Institute
of
Surgical
Research
(US
Army
Burn
Center)
extensively
researched
the
combined
effects
of
silver-nylon
fabric
and
weak
electric
(direct)
current
on
wound
healing
and
published
at
least
13
studies
between
1988
and
2005
[34,36–47].
A
variety
of
animal
models
of
partial
and
full-thickness
burns,
infected
burn
wounds,
excised
burn
wounds,
donor
sites,
and
skin
flaps
evaluated
the
utility
of
silver-nylon
with
and
without
direct
current
on
wound
healing,
microcirculation,
wound
edema,
plasma
protein
extravasation,
and
wound
closure
using
split
thickness
skin
grafts,
autograft/allograft
composite
grafts,
and
dermal
replacement/meshed
autograft
techniques
[34,36–47].
Two
human
trials
were
carried
out,
including
one
study
of
donor
site
healing
[47].
Independently,
Huckfeld
et
al.
demon-
strated
that
weak
direct
current
applied
to
silver-nylon
dressings
could
accelerate
wound
closure
after
split
thickness
skin
grafting
in
humans
[48].
In
the
21st
century,
the
medicinal
use
of
silver
extends
beyond
burn
care
or
wound
dressings.
Nosocomial
infection,
particularly
urinary
tract
infections
and
catheter-associated
bloodstream
infections
are
common
in
hospitalized
patients,
b
u
r
n
s
4
0
s
(
2
0
1
4
)
s
3
–
s
8
S5
and
increase
patient
morbidity,
mortality,
hospital
length
of
stay
and
healthcare
costs
[49].
Central
venous
lines
and
foley
catheters
are
prone
to
the
development
of
biofilms,
which
are
densely
adherent
polysaccharide
structures
that
shelter
bacteria
[50].
Biofilms
change
bacteria
from
a
free
swimming
state
to
a
sessile
state,
where
they
are
sheltered
from
antimicrobial
drugs
[50].
Biofilm
production
and
microorgan-
ism
adhesion
can
be
reduced
by
coating
catheters
with
antiseptics
or
antimicrobial
agents
[49].
Central
venous
and
indwelling
bladder
catheters
treated
with
silver
metal,
silver
oxide,
silver
sulfadiazine,
platinum,
chlorhexidine,
rifampin
and
tetracyclines
have
been
evaluated
in
vitro
and
in
vivo
in
animal
and
human
studies
[12,49].
In
general,
in
vitro
results
are
superior
to
those
seen
in
animal
and
human
models
[12,51,52],
however,
chlorhexidine
(CHG)
and
silver
sulfadia-
zine
(SSD)
have
synergistic
antibacterial
action,
and
central
venous
catheters
coated
with
chlorhexidine/silver
sulfadia-
zine
have
proven
effective
in
clinical
trials
[49,53].
Maki
et
al.
[53]
prospectively
studied
158
patients
(403
catheters)
ran-
domized
to
receive
either
a
standard
CVP
catheter
or
an
antibiotic
coated
(CHG/SSD)
catheter
at
the
University
of
Wisconsin
Hospital.
Antibiotic
catheters
had
a
fivefold
decrease
in
bloodstream
infection
rates
(
p
=
0.03)
and
were
significantly
less
likely
to
be
colonized
at
the
time
of
removal
(
p
=
0.005)
[53].
Borschel
et
al.
evaluated
central
venous
catheters
coated
with
CHG/SSD
in
a
pretest–posttest
cohort
study
at
the
University
of
Michigan
[54].
A
35%
relative
risk
reduction
in
the
catheter-related
bloodstream
infection
rate
was
seen
after
introduction
of
the
coated
catheters,
with
an
associated
cost
reduction
of
$100,000
annually
[54].
Antibiotic-
coated
central
venous
catheter
use
was
also
associated
with
a
22%
reduction
in
the
use
of
vancomycin,
presumably
prescribed
for
Gram
positive
bloodstream
infections
[54].
Silver-coated
endotracheal
tubes
designed
to
lower
the
risk
of
ventilator-associated
pneumonia
have
shown
efficacy
in
both
animal
and
human
studies
[55,56].
The
NASCENT
Randomized
Trial
prospectively
evaluated
2003
patients
requir-
ing
endotracheal
intubation
as
a
multicenter
study
involving
54
centers.
Patients
were
randomized
to
receive
either
silver-
coated
or
conventional
endotracheal
tubes.
Patients
receiving
a
silver-coated
endotracheal
tube
had
a
statistically
significant
reduction
in
the
incidence
of
ventilator
associated
pneumonia
(VAP)
compared
to
those
intubated
with
conventional
tubes
[55].
Silver-coatedendotracheal
tubesalso
delayedtime
toonset
of
VAP
compared
to
uncoated
controls
[55].
Urinary
tract
infections
are
the
most
common
hospital
acquired
infections,
comprising
approximately
40%
of
all
nosocomial
infections
[50].
Up
to
25%
of
hospitalized
patients
have
urinary
catheters
placed
during
their
hospital
stay
[50],
and
more
than
80%
of
hospital
urinary
tract
infections
are
associated
with
the
use
of
a
urinary
catheter
[50].
A
urinary
tract
infection
in
a
patient
with
an
indwelling
catheter
is
termed
a
catheter-associated
urinary
tract
infection
(CAUTI),
which,
by
definition,
becomes
a
complex
UTI.
Biofilm
forma-
tion
commonly
occurs
on
urinary
catheters,
making
treatment
difficult.
In
addition
to
patient
discomfort
and
morbidity,
catheter-associated
urinary
tract
infections
are
a
financial
concern
for
hospitals,
in
that
the
US
Centers
for
Medicare
and
Medicaid
Services
(CMS)
refuses
to
pay
additional
reimburse-
ment
for
this
condition.
Silver-coated
urinary
catheters
have
been
commercially
available
for
over
20
years
[57].
Multiple
publications
suggest
that
silver-alloy
coated
catheters
are
effective
in
reducing
CAUTI
rates
by
up
to
45%
[50,57].
Silver-oxide
coated
catheters
do
not
work
as
well
as
silver-alloy
catheters
[50,57].
Parker
et
al.
in
a
evidence-based
literature
review,
recommend
the
use
of
silver-alloy
coated
catheters
in
patients
requiring
short-
term
(up
to
2
weeks)
bladder
catheterization
as
a
method
to
reduce
bacteria
and
the
risk
of
CAUTI
[50].
While
not
strictly
a
medical
application,
the
antimicrobial
effects
of
silver
ion
are
now
finding
application
in
home
appliances.
Samsung
Electronics
produces
refrigerators
using
silver
trays,
and
washing
machines
containing
nanosilver
particles
that
generate
silver
ions.
The
claimed
benefit
is
to
deodorize
and
sanitize
clothes
against
germs
as
well
as
to
keep
the
internal
parts
of
the
machine
germ-free
[7].
LG
Electronics
markets
refrigerators
using
a
nanosilver
compound
for
antimicrobial
properties
[7].
Hitachi
markets
a
silver-contain-
ing
dishwasher
[8].
Finally,
the
original
use
of
silver
in
medicine
(water
storage
and
purification)
continues
to
find
utility.
In
2009,
Shrestha
et
al.
[58]
published
a
study
examining
the
ability
of
common
household
metal
pots
constructed
of
silver,
copper
or
brass
to
kill
enteric
pathogens
isolated
from
drinking
water
in
Nepal.
Isolates
of
E.
coli,
multidrug
resistant
E.
coli,
Salmonella
paratyphi,
Shigella
species,
and
Vibrio
cholerae
were
placed
in
metal
pots
and
assayed
at
4
h
intervals.
Salmonella
and
E.
coli
were
completely
inhibited
by
24
h
in
all
pots
tested
and
Shigella
were
completely
inhibited
at
24
h
by
copper
and
48
h
by
brass
and
silver
vessels
[58].
Multidrug
resistant
E.
coli
wascompletely
inhibitedby
silver
and
brass
at
24
h
and
by
copper
at
48
h
[58].
The
use
of
silver
to
purify
water
has
thus
traveled
over
23
centuries
from
Macedon
to
Nepal,
traversing
the
moon
along
the
way.
3.
Discussion
The
medicinal
use
of
silver
is
not
a
new
idea.
Silver
ion
has
been
employed
as
an
antimicrobial
for
several
millennia,
the
discovery
of
this
indication
preceding
the
discovery
of
microbes
or
the
Germ
Theory
of
Disease
by
several
centuries.
True
allergy
is
rare,
and
resistance
has
never
become
clinically
significant.
Silver
is
not
an
eye
or
skin
irritant
or
skin
sensitizer,
human
carcinogen
or
mutagen
[4,59].
Adverse
effects
such
as
argyria
are
almost
always
related
to
inappro-
priate
use,
usually
from
oral
ingestion
of
colloidal
silver
solutions.
There
is
no
accepted
medical
indication
for
the
use
of
oral
colloidal
silver.
Ionic
silver,
on
the
other
hand,
is
routinely
added
to
drinking
water
for
disinfectant
purposes
without
any
harm
to
health.
When
the
safety
of
silver
is
debated,
common
sense
must
prevail.
There
are
few,
if
any
compounds
in
contemporary
medical
practice
with
as
lengthy
a
history
as
silver.
Conflict
of
interest
statement
The
authors
have
received
research
support
or
consulting
fees
from
Argentum
Medical,
LLC
and
are
members
of
the
Argentum
Medical
Advisory
Board.
b
u
r
n
s
4
0
s
(
2
0
1
4
)
s
3
–
s
8S6
r
e
f
e
r
e
n
c
e
s
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