The use of iodine as an
antiseptic agent
A review of the discovery, uses and evolution of iodine and its compounds
as antiseptics and the development of povidone-iodine
odine is one of the longest estab­
I
lished antiseptics; a tincture was used
by a French surgeon in 1837, and the
use of iodine during the American Civil
War was widespread1. For many years
various preparations containing iodine
have been available for wound care,
including tinctures, solutions in potas­
sium iodide, and the compound called
iodoform23. All had disadvantages, caus­
ing local pain and tissue irritation,
effects which probably precluded a more
widespread use of iodine in the past.
Povidone-iodine, 'the tamed iodine',
was devised and introduced about 40
years ago, and has proved an easier-to-use
and safer form of iodine4. Its clinical appli­
cations are ubiquitous, ranging from dis­
infection of inanimate objects and intact
skin to therapy for all types of wounds, as
well as treatment of infections of the oral,
peritoneal and vaginal cavities.
This review outlines the nature and
sources of iodine, briefly com m enting
on its general uses and its antibacterial
activity and safety, and considers the use
and efficacy of povidone-iodine in
wound care.
Nature, sources and uses of iodine
Elemental iodine (from the Greek
ioeides, violet coloured) was isolated in
1811. It Is a violet-black non-m etallic
crystalline solid (Fig 1), atom ic weight
126.904, which readily sublimes to form
a pungent irritating violet vapour (Fig
2). Iodine, fluorine, chlorine, bromine,
together with the artificial element asta­
tine, comprise a group of elements
called the halogens (from the Greek: salt
formers). Iodine salts are widely dis­
tributed; small concentrations (up to
0.001 mg/mL) are found in sea water but
higher concentrations are found in fish,
oysters and certain seaweeds. Commer-
JOURNAL OF W O U N D CARE SEPTEMBER, VOL 7, NO 8, 1998
J.C. Lawrence, BSc, PhD, C B iol, FIBiol, Senior
Research Fellow, W o u n d Healing Research U nit,
U nive rsity o f W ales C ollege o f M edicine, C ardiff, U K
Iodine; lodophore; Povidone-iodine
dally, iodine used to be obtained by
burning seaweed (kelp), but it now
comes mostly from Chile saltpetre,
which contains small quantities of
sodium iodate.
Iodine is an essential nutrient required
for synthesis of thyroid hormones. The
thyroid gland contains about 95% of total
body iodine (5000-8000pg); the plasma
concentration ranges from 0.5-1,5(jg/L.
The body requires 100-200pg iodine per
day; an intake of less than 50pg may
lead to deficiency diseases. Fish is the
best source of iodine and prolific fish
eaters may ingest several milligrams of
iodine a day.
Iodine compounds have diverse uses:
potassium iodate and sodium iodide are
used to treat iodine deficiency diseases,
other iodine salts are used in expecto­
rants and as diuretics3. Silver iodide is
used in photography and organic iodine
in X-ray contrast media3.
Povidone-iodine (polyvinyl-pyrrolidone-
iodine complex) is an iodophor, a loose
com bination of iodine with a non-ionic
surfactant in which some of the iodine
may be available. The antibacterial activ­
ity of such iodine is identical to that of
iodine dissolved in ethanol or solubilised
in potassium iodide. Iodophors provide a
stable solution of iodine whereas alterna­
tives can lose strength by volatilisation,
and may precipitate on dilution. Povi­
done-iodine is a brown, amorphous,
water-soluble powder containing 9-12%
available iodine (Fig 3).
The iodine in povidone-iodine has vir­
tually no vapour pressure hence no
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iodine loss occurs and there is no signifi­
cant odour4. It is also non-staining - the
brown colour imparted to skin, fabrics
and so on during its use can be readily
removed4. Loss of the brown colour from
povidone-iodine is always associated
with loss of antibacterial properties5.
Some 30 years after the synthesis of
povidone-iodine a paradox in the
behaviour of 10% solutions was reported:
its antibacterial action increased with
degree of dilution6. This effect, which is
maximal between 1:10 and 1:100 dilu­
tions, has been fully described, together
with observations on povidone-iodine's
mechanism of action7. The behaviour of
povidone-iodine in aqueous media has
recently been considered together with
other aspects of this iodophor8.
Around 15 years ago, another iodine
complex material, cadexomer iodine,
became available. This is a polysaccha­
ride, a three-dimensional starch lattice
containing 0.9% iodine. Cadexomer
iodine has a high absorptive capacity (lg
can absorb up to 7mL fluid)9. When fluid
is absorbed, iodine is slowly released; it is
suggested that this permits maintenance
of iodine levels in the wound bed
whereas other forms of iodine are rapidly
broken down9. However, there seems to
be no information concerning either the
rate of release of iodine from cadexomer
iodine or the extent to which this iodine
permeates beyond its carrier. Cadexomer
iodine is a purpose-designed wound
dressing; being insoluble, it is unlikely to
have other applications. It is not consid­
ered further here and readers are referred
to recent reviews911.
There is an enormous literature con­
cerning iodine and wound care. Despite
the long-standing availability and use of
iodine some aspects remain controver­
sial, particularly its value in the care of
421

Fig 1. Solid iodine
bacterially colonised wounds. For exam­
ple, a recent authoritative review12 states:
'The use of povidone-iodine is not
recommended for open wound treat­
ment. It has been shown to be toxic to
skin cells in vitro and to have a limited
antimicrobial effect in vivo'; however,
another authority13 comments: 'There
appears to be no evidence that any of the
povidone-iodine preparations reviewed,
other than detergent-containing prepara­
tions, are detrimental to overall wound
healing.' The merits of both of these
statements are considered in this review.
Antibacterial properties
Iodine is a highly reactive element with
a particular affinity for double bonds, a
m ajor factor in its excellent germicidal
efficacy which includes bacteria, bacte­
rial spores, fungi, protozoa and viruses.
Povidone-iodine solutions contain com ­
plex iodine, I3, in much the same way as
do solutions of iodine in potassium
iodide. The carrier, polyvinylpyrroli­
done, originally used as a plasma vol­
ume expander, is a hydrophilic polymer
lacking any intrinsic antibacterial activ­
ity; it has an affinity to cell membranes
and thus can deliver diatomic iodine, I2,
to bacterial cell surfaces14.
Iodine has two important outstanding
characteristics: it is non-selective in action
and all bacteria are killed by similar con­
centrations; also it is bactericidal and not
bacteriostatic15. Povidone-iodine's anti­
bacterial action was thoroughly explored
many years ago16. Iodine, including povi­
done-iodine, is an effective sporicide17 but
it has long been recognised that disinfec­
tion times vary widely depending on
whether the contaminated surface is wet
or dry15. Times can vary from a few min­
utes to several hours.
There are discrepancies in reported
minimal lethal concentrations of iodine
I to vegetative bacteria and in killing times.
422
DISCUSSION
Fig 2. Iodine vapour
Sykes15 suggests that these differences are
due to variations in methodology
together with the fact that the presence
of organic matter has a marked depres­
sant effect on minimum lethal concentra­
tions of iodine. The more recent careful
work by Lacey and Catto5 not only con­
firms Sykes' comments but also shows
that, in the absence of inhibitors, disin­
fection is rapid (probably less than 10 sec­
onds) and that as little as 1 x 1 0 16g iodine
will destroy one bacterial cell.
Methicillin-resistant Staphylococcus aureus
Although it has been claimed that iodine
may be ineffective against some strains
of methicillin-resistant Staphylococcus
aureus (MRSA)18, such findings may be
attributable to methodology5. Other
reports claim that povidone-iodine is
highly active against various strains of
MRSA5'15'21 and the value of povidone-
iodine in helping control MRSA out­
breaks is generally recognised22,23.
Although other antiseptics are usually
cidal to MRSA they frequently take
longer to be effective; povidone-iodine
kills bacteria rapidly, including species
resistant to other antiseptics5,21,24,25.
Development of bacterial resistance to
povidone-iodine is most unlikely because
resistance to this, or any other anti­
bacterial agent, needs to be associated
with some biochemical and/or structural
change within the bacterial cell involv­
ing formation of novel proteins. The
formation o f proteins capable of resist­
ing the destructive capacity of iodine
would be surprising. This non-develop­
m ent of resistance to povidone-iodine
has recently been re-examined26.
Safety
In com m on with most, if not all, thera­
peutic materials, iodine and its com ­
pounds are not hazard free. However, in
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Fig 3. Povidone-iodine powder
normal controlled use povidone-iodine
is a safe substance. A variety of toxic
effects can be associated with iodine,
including mental depression, nervous­
ness, insomnia, myxoedema, hyper­
sensitivity and skin reactions3. The
likelihood of encountering adverse
effects depends to some extent on the
concentration and the particular use of
povidone-iodine. Thus, although iodine
can be absorbed through the normal
skin of children, oral mucosa, vaginal
mucosa, burns and other skin wounds20,
absorption is likely to be greatest
through damaged tissue. Absorption can
cause elevated iodine blood levels, ele­
vated protein-bound iodine and thyroid
abnormalities; however, clinical mani­
festations such as hypothyroidism are
unusual but children, especially neonates,
may be at greater risk27.
Povidone-iodine may have a positive
benefit/risk ratio in the treatm ent of
burns28 but iodine absorption can cause
metabolic and toxic complications29,30; it
is therefore suggested that iodine should
not be used on burns exceeding 20%
body surface area30,31. However, absorbed
iodine is quickly excreted, provided
renal function is unimpaired32. Most
absorbed iodine becomes rapidly
attached to tyrosine residues in serum
albumen, though small amounts may
attach to the globulins33. The pharmaco­
dynamics and toxicity of povidone-
iodine have been reviewed14,34.
The incidence of allergy and contact
dermatitis following application of povi­
done-iodine to normal intact skin or
mucosa is low (two allergic reactions
from 5 ,000 applications), but 10 times
higher in patients with known aller­
gies14. A case of anaphylaxis from povi­
done-iodine has recently been reported,
the authors suggesting that this antisep­
tic should be stringently avoided if there
is a suspected allergy to it or iodine35.
RE SEPTEMBER, on December
VOL 7, N29, O 2016.
8, 1998

It is generally agreed that povidone-
iodine has some degree of toxicity to
cells but considerable controversy exists
concerning the extent and significance
of such toxicity as far as the use of povi­
done-iodine in relatively small wounds
is concerned1213. The situation is exacer­
bated when, on one occasion, a recognised
authority reports that povidone-iodine
solution is not deleterious36 yet eight
years later the same author states that
iodine is a 'poison'37.
Most of the toxicological evidence has
been derived in vitro and its relevance to
clinical practice is often unclear. More­
over, there is confusion concerning the
nature of povidone-iodine solutions
which may be a simple solution or may
also contain detergent; such factors,
together with concentration, are rele­
vant to both safety and efficacy38.
Numerous references are listed in recent
reviews12'13'38.
Disinfection
The reliable broad-spectrum disinfecting
power of iodine made it the choice of
NASA for disinfecting space modules39.
Aqueous povidone-iodine is applied to
dry surfaces which are free of visible
organic material and allowed to remain
for 10 minutes prior to removal with a
moistened wipe followed by drying40.
Sometimes iodine's reactivity renders it
unsuitable for use on some materials;
practical guidance on suitable antisep­
tics for specific purposes is available41.
The efficacy and value of povidone-
iodine as a skin or hand disinfectant is
rarely disputed. Numerous papers testify to
its efficacy42"16. Either aqueous or alcoholic
solutions can be used, the latter being
preferable if the iodine is to be allowed to
remain in situ. Treated areas of the skin
stain brown (readily removed with water)
and areas that have been missed are there­
fore usually immediately apparent. Partic­
ular care is needed with hands since
important areas can be readily missed47. If
sporicidal action is required, aqueous povi­
done-iodine must be applied and kept
moist for 20 minutes48.
Povidone-iodine in wound care
Burns
There are many reports concerned with
topical povidone-iodine therapy for
burns (Fig 4). A study of 24 patients
showed povidone-iodine ointm ent to be
as effective as topical silver nitrate49, a
widely accepted treatm ent. Others have
reported povidone-iodine ointm ent to
JOURNAL OF W O UN D CA RE SEPTEMBER. VOL 7, NO 8. 1998
DISCUSSION
be bacteriologically effective50 and of
similar value to well-established burn
therapies such as silver sulphadiazine or
sulfamylon51. A comparative study of
povidone-iodine ointm ent with silver
sulphadiazine cream showed that bacte­
rial counts on the wound surface were
lower with the ointm ent52.
A South African study used povidone-
iodine ointm ent or cream alone or with
a proprietary proteolytic agent; the pro­
teolytic agent did not influence results
and the best results were obtained with
the cream53. A separate study showed that
5% povidone-iodine cream was both safe
and effective54. However, possible toxic
complications considered earlier may pre­
clude use of povidone-iodine on burns
exceeding 20% body surface area30-31.
Topical antimicrobial therapy in burns
is normally a prophylactic measure to
reduce the incidence of acquisition of
potentially pathogenic bacteria55 56. The
Birmingham Burns Unit reported that
povidone-iodine cream exerted signifi­
cant antibacterial prophylaxis in burns
but some alternatives appeared better57,
notably compounds containing silver.
Variation in treatment regimens between
different centres could account for at
least some contradictory reports. It has
been suggested that, because serous exu­
date inactivates iodine, eight hourly
dressing changes are recommended58.
Interestingly, aqueous povidone-
iodine appears to be an excellent topical
antibacterial prophylactic for burned
sites that cannot be dressed con ­
veniently57; detailed inform ation on
burn care is given in standard texts5960.
Acute wounds
An extensive surgical evaluation of povi­
done-iodine was made over 30 years ago
on prospective operation sites and
patients with infected wounds61. A consid­
erable decrease in bacterial numbers was
detected in infected wounds after 24
hours of treatment; the povidone-iodine
was usually applied every six hours. In the
case of burns, this was associated with a
high take of skin grafts. Unfortunately, no
comparative data with any alternative
antibacterial therapy was presented. A
more recent report makes similar claims62,
again without any comparator except for
the take of skin grafts where it was found
that povidone-iodine dressings were
superior to non-medicated dressings.
Reports concerning the prophylactic
value of povidone-iodine in surgery are
controversial. A study of the sepsis rate in
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Fig 4. Soon after burning, wounds often
show gross oedema
192 wounds randomly allocated to either
topical cephaloridine or povidone-iodine
spray found cephaloridine to be a superior
prophylactic, but a significant difference
was found only with potentially contami­
nated wounds63. By contrast, a prospective
randomised prophylactic study of 210
patients about to undergo acute abdomi­
nal surgery compared topical povidone-
iodine with systemic tobramycin plus
lincomycin or no antibacterial prophy­
laxis; both antibacterial therapies signifi­
cantly decreased wound sepsis compared
with no prophylaxis64.
Chronic wounds
There is a paucity of published informa­
tion concerning treatm ent of chronic
wounds with povidone-iodine. In 1965
it was reported that application of povi­
done-iodine to a series of 25 patients
with chronic and previously unrespon­
sive leg ulcers resulted in 15 being
healed within four weeks to six m onths
(the maximum period of the study) and
three further cases improved; little
bacteriological change was observed
after six weeks of treatm ent, except in
ulcers that healed within this tim e65.
Topical antiseptics have been shown to
be effective in experimental wounds66
but others question their clinical value
as far as the therapy of chronic skin
ulcers is concerned67'68.
In recent years some clinicians have
used a mixture of sugar and povidone-
iodine to treat refractory cutaneous
ulcers and other wounds69 71. However,
none of these is a comparative study and
none contains significant bacteriological
■423

information, but all claim good results.
In one study, about a fifth of the patients
had previously been unsuccessfully
treated with povidone-iodine71. Contact
dermatitis has been reported following
povidone-iodine plus sugar therapy72.
Discussion
There is little doubt that iodine is one of
the most powerful antiseptics available.
The advent of povidone-iodine over­
came the problems of irritancy associ­
ated with other iodine preparations
when used on raw surfaces. Few, if any,
alternative antiseptics have such ubi­
quitous clinical applications, many are
toxic, and most have other disadvan­
tages, such as having selective action.
Iodine is the only antiseptic which will
eradicate spores.
The value and efficacy of iodine as a
skin disinfectant has long been recog­
nised and rarely questioned. Povidone-
iodine is widely used for pre-operative
disinfection of surgeon's hands and
prospective operation sites. Because
povidone-iodine solutions are brown,
missed areas are easily seen but the
colour can be washed away with water.
Topical povidone-iodine almost cer­
tainly provides effective antibacterial
prophylaxis in wound care, especially in
burns49-51'57. However, its therapeutic
value in wounds is less clear. Numerous
studies describe its use but few compare
and contrast it with other antibacterial
therapies or give detailed bacteriological
inform ation. Nevertheless, povidone-
iodine is widely recommended as part of
standard wound care therapies41'73'74.
Current fashion denigrates the use of
antiseptics, including povidone-iodine,
on wounds. It is not disputed that iodine
can be absorbed by the body, particu­
larly through extensive wounds or intra-
peritoneal irrigation, and it must
therefore be used with caution in
patients who have pre-existing thyroid
or renal disorders.
The concern is with relatively small
wounds, following laboratory studies of
capillary blood flow in a rabbit ear
cham ber75, and on fibroblasts in tissue
culture76. The authors never suggested
banning antiseptics, only that they
should be used with caution77. As one
povidone-iodine manufacturer points
out, there is little evidence that it inter­
feres with wound healing78. In vitro toxi­
city studies of iodine and other
antiseptics date from 1 9 1679. Compared
with many other antiseptics, iodine is
424
DISCUSSION
relatively non-toxic to adult skin slices
maintained in vitro, with a low toxicity
compared with substances such as cop­
per sulphate or mercuric chloride80.
There is a paucity of bacteriological
studies concerning possible therapeutic
effects of iodine in colonised chronic
wounds. In 1919, Fleming thought that
antiseptics would not disinfect a wound
which he demonstrated with a model81.
Others took an opposite view, believing
antiseptics to be useful in wound care;
however, the irritancy of contemporary
iodine solutions led Dakin to use a
hypochlorite although he recognised
iodine to be a particularly efficacious
antiseptic82.
Experiments suggest that a single
application of povidone-iodine solution
to colonised burns reduces bacterial
numbers at the surface but with little
apparent effect on bacterial numbers in
deeper layers83. The effect of repeated
applications of iodine on the bacterial
content of colonised tissues is, at pre­
sent, unknown.
A laboratory model of an exuding
wound used to investigate the possible
practical antibacterial efficacy of proto­
type dressings medicated with povidone-
iodine has yielded encouraging results84
but properly designed clinical studies are
needed. Disappointingly, the sole clinical
study of a proprietary povidone-iodine-
medicated dressing contains limited bac­
teriological information85.
It may be that topical povidone-iodine
will not disinfect a bacterially colonised
wound because proteins, especially albu­
min present in serum, rapidly inactivate
iodine. Calculation suggests that the
double bonds present in the protein
contained within a square centimetre of
exudate-soaked tissue 0.5cm thick would
neutralise about 0.004g iodine. However,
the three proprietary iodine-medicated
dressings contain less than 0.004g iodine
per cm 2 of dressing surface; a single
application is thus unlikely to disinfect
much more than the tissue surface.
The situation is further complicated
because wounds continuously ooze and
this exudate replenishes the iodine­
inactivating proteins. Meanwhile wound
bacteria multiply and tend to replace
those that have been killed. Exudate
passing through the medicated dressing
into any overlying secondary dressing
will elute some iodine away from the
wound surface. Whether prompt replace­
ment of exhausted dressings confers
bacteriological benefit is unknown.
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Some clinicians may have over-expec­
tations of antiseptic efficacy. The pro­
phylactic power of povidone-iodine is
unlikely to match that of antibiotics in
all circumstances but the ethics of using
prophylactic antibiotics are often dubi­
ous. Antibiotics tend to be more expen­
sive and their use, particularly topical
use, can give rise to resistant strains. Bac­
terial resistance to povidone-iodine is
unknown hence its value in coping with
MRSA. Treating wounds showing clear
clinical evidence of sepsis with antisep­
tics is unlikely to result in cure; it has
long been widely recognised that the
treatment of choice is a course of appro­
priate systemic antibiotics.
However, topical use of povidone-
iodine will prevent many wounds
becoming colonised with potentially
pathogenic bacteria and thus prevent
some, at least, from becoming infected.
Moreover, such use of povidone-iodine
helps contain; wound bacteria, thus
minimising their spread to the general
environm ent and enhancing infection
control; these aspects are particularly
important in patient treatment areas. ■
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