The Proven Power and Safety of Iodine
Introduction
For more than 150 years, iodine has been used for the prevention of infection and for the treatment of wounds. Use of its beneficial impact had even existed much earlier without any actual awareness of the active substance. Already in the Greek Age (4th century BC), Theophrastus, Aristotle’s pupil and first expert in medical plants, described the use of seaweeds and other plants in refreshing and relieving pain after sun burn wounds. During Napoleon’s Egyptian campaign (1798-1801), wounded soldiers were treated with extracts from seaweeds and other plants enriched with iodine at high concentrations
from sea water (1). Also during the American Civil War (1863), the use of iodine for disinfections
was widespread (2).
Even if iodine-containing plants were well used before, the natural element iodine was only discovered in 1811 by the Dijon chemist Bernard Courtois. It was given its name from the Greek ioeides meaning “violet coloured”, because of the intensely violet colour of its vapours (1). Iodine’s bacteria killing (bactericidal) action was first described scientifically by DAVAINE (3) in 1880 and it was only between the 19th and 20th century that surgeons started to use iodine as a preoperative disinfectant.
It was the development of the iodophors (substances that can carry Iodium) which made the large-scale use of this highly effective microbiocidal possible.
With a history spanning almost two centuries, the antibacterial activity of iodine is superior compared to other products and, in contrast with antibiotics and other antiseptics, it seems to have no resistance problem. Organically bound iodine has all the characteristics to become the first choice antiseptic, as will be discussed.
Elemental iodine is a violet-black non-metallic crystalline solid, with an atomic weight of 126.904, which
readily sublimes to form a pungent irritating violet vapour. Its solubility in water is only 1:3000.
Iodine, fluorine, chlorine, bromine comprise a group of elements called the halogens (from the Greek : salt formers). Iodine salts are widely distributed (sea water, fish, oysters and certain seaweeds). Commercially, iodine used to be obtained by burning seaweed (kelp), but it now comes mostly from Chile saltpetre, which contains small quantities of sodium iodate (6).
Iodine is an essential nutrient required for synthesis of thyroid hormones and the body requires 100-200µg iodine per day (6). Iodine compounds have diverse uses : potassium
iodate and sodium iodide are used to treat iodine deficiency diseases, other iodine salts are used in expectorants and as diuretics (7). Iodine has traditionally been available in Solution
2%, Tincture 2%, Strong Solution 5% and Strong Tincture 7%. It has been demonstrated that, with these old formulations and in a normal solution at least seven iodine forms are present in a complex equilibrium with molecular iodine (I2), which is primarly responsible for the antimicrobial efficacy (8).
The Role of Iodine in Antisepsis
The development of new formulations, such as iodophors, has resulted in a major break-through
in the use of iodine containing agents : toxicity has been eliminated, the formulations are more stable and despite a lesser concentration of iodine, the same high level of clinical efficacy is maintained (13, 20).
2. Antiseptics properties
As a general rule, less is known about the mode of action of antiseptic agents compared to antibiotics. Antiseptic agents usually have a broader spectrum of activity than antibiotics and, while the latter group tends to have specific intracellular targets, the former group may have
multiple targets (7).
Although the precise mechanism of iodine has not been completely determined, it has been suggested that the lethal effect of iodine on microorganisms can be explained as follows: iodine rapidly penetrates the cell wall and proceeds to dislocate protein synthesis, it disrupts the function of respiratory chain enzymes and interferes with lipid membrane and nucleic acid function through several diverse mechanisms of action (7, 21).
Less is known about the antiviral action of iodine, but it has been demonstrated that nonlipid viruses and parvoviruses are less sensitive than lipid enveloped viruses (22). Similarly to bacteria, it is likely that iodine attacks the surface proteins of enveloped viruses, but they may also destabilize membrane fatty acids by reacting with unsatured carbon bonds (23).
Antimicrobial activity of antiseptics can be influenced by many factors such as formulation effects, presence of an organic load, synergy, temperature, dilution, and test method (24, 25). More than 100 articles have been written specifically about iodine and its antiseptic activity, comparing it to
other antiseptics and antibiotics.
The whole literature, a mixture of laboratory, animals and human studies, using a considerable number of different preparations at different concentrations, is stating without doubt the superiority of iodine, in topical antisepsis, compared to other substances. Iodine has been shown to be the only agent that is
simultaneously active against gram+, gram-, spores, amoebic cysts, fungi, protozoa and yeasts (26, 27), and MRSA, while other antiseptic agents, as chlorhexidine, never achieved a total kill against all the strains tested (both in clinical and laboratory conditions) (28-30).
3. Effect on the wound healing process
It is a common belief that, the stronger the bactericide effect of an antiseptic agent, the more deleterious is its effect on living tissue. Probably because of this belief, many surgeons and
general practicioners have long been convinced that iodine preparations, because of their extreme bactericidal effect, did not really promote good wound healing.
Indeed, older studies and preparations have shown impaired wound healing and reduced wound strength
with the use of iodine (33, 34). However, newer literature has demonstrated that
many of those older studies confused different study conditions: animal versus human research, in vivo versus in vitro conditions and differences in preparations of iodine at different concentrations.
The recent literature has demonstrated that the conclusions of those older studies are not always reliable
and comparable (35). Very recent articles seem to go even a step further, demonstrating not only the absence of a deleterious effect on the wound healing process, but also indicating the presence of a beneficial effect, based on a molucular explanation. Nowadays, new formulations seem to have reached a great improvement (not jeopardizing proliferation of fibroblasts and epithelial cells, neither collagen production) in wound healing, if compared to the old iodine containing agents (13).
Data from MOORE (36) proposed a mechanism additional to iodine anti-bacterial activity in wound healing. He demonstrated that the delivery of iodine to nonactived macrophages within the chronic wound may induce TNFa as a primary event. As a consequence, iodine induces a fresh influx of macrophages and T helper cells, which are considered to play a positive role in modulating wound healing (36).
BENNET, in 2001, proved that PVP-I significantly enhanced angiogenesis (37). Very recently, FUMAL showed how PVP-I increased significantly the healing rate and reduced the healing time by 2-9 weeks ; histologically, PVP-I applications did not alter the microvessels and did not significantly
reduce the density in dendrocytes and fibroblasts (while other two agents tested, silver sulfadiazine and chlorhexidine digluconate, appeared to alter the superficial microvasculature inclunding the dendrocyte population) (38). SCHMIDT reported a possible additional mechanism :
cadexomer iodine formulations may modulate the redox environment of wounds and hence contribute beneficially to wound healing (39). Finally, GILCHRIST in ’97 wrote an important report of
a consensus meeting on the use of iodine in wound care : the overall impression was that the product (especially cadexomer iodine) does have a role in enhancing healing in chronic wounds (35).
In conclusion, the literature seems to have moved away from earlier criticism of iodine with reports of
deleterious effect of iodine on the wound healing process, towards a much more positive attitude with an
even beneficial stimulating effect on wound healing.
The Role of Iodine in Antisepsis
Table II shows the descending order of resistance of different pathogenic species to antiseptics and disinfectants (31).
Table II
Descending order of resistance to antiseptics and disinfectants
Prions
Coccidia
Spores
Mycobacteria
Cysts
Small non-enveloped virus (polio-virus)
Trophozoites
Gram-negative bacteria (non sporulating) (Pseudomonas)
Fungi
Large non-enveloped viruses
Gram positive bacteria (S. Aureus)
Lipid enveloped virus (HIV, HBV, MOLLUSCUM)
Given that iodine containing antiseptic agents have been in extensive clinical use in hospital for over 150
years without development of resistance, it is tempting to hypothesize that it is the actual mechanism of action of iodine, which stops the evolution of resistance: these various iodine-directed mechanisms of action occur with such speed at different and dispersed target sites that even with the genetic versatility of S. aureus they prove indefensible and rapidly lethal.
5. Contraindications
Adverse effects of povidone-iodine have been rarely published in the literature and only in sporadic case
reports.
Irritative contact dermatitis (53) and acute allergic reactions (54) caused by PVP-I have been reported.
Epicutaneous testing revealed hypersensitivity against PVP-I in less than 1% of 6000 tested patients (55), while other authors never noted allergy towards povidoneiodine during many years of use (56).
It should be stressed that all publications on adverse effects or possible contraindications for povidone-iodine are sporadic case reports often with a questionable clinical relevance.
Conclusion
For more than 2000 years, iodine-containing plants (first) and iodine extracts and preparations (later) have been used for the prevention of infection and the treatment of wounds.
A large amount of published evidence is available in support of the use and safety of iodine.
1. As to the bactericidal activity, few, if any, alternative antiseptics have such ubiquitous clinical applications as iodine-derivated products. There seems to be an almost universal agreement in the literature that the antibacterial activity of PVP-I is superior compared to other products. In most of the studies, it proved to be superior to chlorhexidine and to other antiseptics in assessments of
disinfection performance against MRSA, fungi and viruses, being the only one able to eradicate spores (26, 31).
2. In contrast with antibiotics and other antiseptics, povidone-iodine seems to have no real resistance problem. However, several authors concluded that the problem of growing resistance against other antiseptics and antibiotics (21) and the existence of cross-resistance among these (24, 25, 40), with the exception of PVP-I, should turn us to use more and more iodine preparations (21, 31, 43).
3. After reviewing the literature, it seems that PVP-I has all the characteristics to become the first choice antiseptic.
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The above has been excerpted from the scientific publication listed below.
Acta chir belg, 2003, 103, 241-247
G.Selvaggi, et al
Dept Surgery, Gent University Hospital, Belgium