ANTISEPTIC & DISINFECTANTS - types and mode of action

Antiseptics (from Greek αντί - anti, '"against" + σηπτικός - septikos, "putrefactive") are antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction. Antiseptics are generally distinguished from antibiotics by their ability to be transported through the lymphatic system to destroy bacteria within the body, and from disinfectants, which destroy microorganisms found on non-living objects. Some antiseptics are true germicides, capable of destroying microbes (bactericidal), whilst others are bacteriostatic and only prevent or inhibit their growth. Antibacterial are antiseptics that have the proven ability to act against bacteria. Microbicides which kill virus particles are called viricides or antivirals.

Usage in surgery
The widespread introduction of antiseptic surgical methods followed the publishing of the paper Antiseptic Principle of the Practice of Surgery in 1867 by Joseph Lister, inspired by Louis Pasteur's germ theory of putrefaction. In this paper he advocated the use of carbolic acid (phenol) as a method of ensuring that any germs present were killed. 

Some of this work was anticipated by:

For the growth of bacteria there must be a food supply, moisture, in most cases oxygen, and a certain minimum temperature. These conditions have been studied and applied in preserving of food and the ancient practice of embalming the dead, which is the earliest known systematic use of antiseptics.
In early inquiries, there was much emphasis on the prevention of putrefaction, and procedures were carried out to find how much of an agent must be added to a given solution in order to prevent development of undesirable bacteria. However, for various reasons, this method was inaccurate, and today an antiseptic is judged by its effect on pure cultures of defined pathogenic circular single helix microbes and their vegetative and spore forms. The standardization of antiseptics has been implemented in many instances, and a water solution of phenol of a certain fixed strength is now used as the standard to which other antiseptics are compared.

Some common antiseptics

Alcohols

Most commonly used are ethanol (60–90%), 1-propanol (60–70%) and 2-propanol/isopropanol (70–80%) or mixtures of these alcohols. They are commonly referred to as "surgical alcohol". Used to disinfect the skin before injections are given, often along with iodine (tincture of iodine) or some cationic surfactants (benzalkonium chloride 0.05–0.5%, chlorhexidine 0.2–4.0% or octenidine dihydrochloride 0.1–2.0%).

Quaternary ammonium compounds

Also known as Quats or QAC's, include the chemicals benzalkonium chloride (BAC), cetyl trimethylammonium bromide (CTMB),cetylpyridinium chloride (Cetrim, CPC) and benzethonium chloride (BZT). Benzalkonium chloride is used in some pre-operative skin disinfectants (conc. 0.05–0.5%) and antiseptic towels. The antimicrobial activity of Quats is inactivated by anionic surfactants, such as soaps. Related disinfectants include chlorhexidine and octenidine.

Boric acid

Used in suppositories to treat yeast infections of the vagina, in eye washes, and as an antiviral to shorten the duration of sore attacks. Put into creams for burns. Also common in trace amounts in eye contact solution. Though it is popularly known as an antiseptic, it is in reality only a soothing fluid, and bacteria will flourish comfortably in contact with it.

Brilliant Green

A triarylmethane dye still widely used as 1% ethanol solution in Eastern Europe and ex-USSR countries for treatment of small wounds and abscesses. Efficient against gram-positive bacteria.

Chlorhexidine Gluconate

A biguanidine derivative, used in concentrations of 0.5–4.0% alone or in lower concentrations in combination with other compounds, such as alcohols. Used as a skin antiseptic and to treat inflammation of the gums (gingivitis). The microbicidal action is somewhat slow, but remnant. It is a cationic surfactant.

Hydrogen peroxide

Used as a 6% (20 Vols) solution to clean and deodorize wounds and ulcer. More common 3% solutions of hydrogen peroxide have been used in household first aid for scrapes, etc. However, even this less potent form is no longer recommended for typical wound care as the strong oxidization causes scar formation and increases healing time. Gentle washing with mild soap and water or rinsing a scrape with sterile saline is a better practice.

Iodine

Usually used in an alcoholic solution (called tincture of iodine) or as Lugol's iodine solution as a pre- and post-operative antiseptic. No longer recommended to disinfect minor wounds because it induces scar tissue formation and increases healing time. Gentle washing with mild soap and water or rinsing a scrape with sterile saline is a better practice. Novel iodine antiseptics containing povidone-iodine(an iodophore, complex of povidone, a water-soluble polymer, with triiodide anions I₃^-, containing about 10% of active iodine) are far better tolerated, don't affect wound healing negatively and leave a deposit of active iodine, creating the so-called "remnant," or persistent, effect. The great advantage of iodine antiseptics is the widest scope of antimicrobial activity, killing all principal pathogens and given enough time even spores, which are considered to be the most difficult form of microorganisms to be inactivated by disinfectants and antiseptics. 

Mercurochrome

Not recognized as safe and effective by the U.S. Food and Drug Administration (FDA) due to concerns about its mercury content. Other obsolete organomercury antiseptics include bis-(phenylmercuric) monohydrogenborate (Famosept).

Manuka Honey

Recognized by the U.S. Food and Drug Administration (FDA) as a medical device for use in wounds and burns. Active +15 is equal to a 15% solution of phenol.

Octenidine dihydrochloride

A cationic surfactant and bis-(dihydropyridinyl)-decane derivative, used in concentrations of 0.1–2.0%. It is similar in its action to the Quats, but is of somewhat broader spectrum of activity. Octenidine is currently increasingly used in continental Europe as a QAC's and chlorhexidine (with respect to its slow action and concerns about the carcinogenic impurity 4-chloroaniline) substitute in water- or alcohol-based skin, mucosa and wound antiseptic. In aqueous formulations, it is often potentiated with addition of 2-phenoxyethanol.

Phenol (carbolic acid) compounds

Phenol is germicidal in strong solution, inhibitory in weaker ones. Used as a "scrub" for pre-operative hand cleansing. Used in the form of a powder as an antiseptic baby powder, where it is dusted onto the navel as it heals. Also used in mouth washes and throat lozenges, where it has a pain killing effect as well as an antiseptic one. Example: TCP. Other phenolic antiseptics include historically important, but today rarely used (sometimes in dental surgery) thymol, today obsolete hexachlorophene, still used triclosan and sodium 3,5-dibromo-4-hydroxybenzenesulfonate (Dibromol).

Sodium chloride

Used as a general cleanser. Also used as an antiseptic mouthwash. Only a weak antiseptic effect, due to hyper osmolality of the solution above 0.9%.

Sodium hypochlorite

Used in the past, diluted, neutralized and combined with potassium permanganate in the Daquin's solution. It is now used only as disinfectant.

Calcium hypochlorite

Used by Semmelweis, as "chlorinated lime", in his revolutionary efforts against childbed fever.

Sodium bicarbonate (NaHCO3) 

Has antiseptic and disinfectant properties.

Terpenes

Are the main type of compound found in essential oils, and some having reasonably strong antibacterial, antifungal and antiviral properties For example Terpinen-4-ol is found in Tea tree oil.
Evolved resistance
Stuart B. Levy, in a presentation to the 2000 Emerging Infectious Diseases Conference, expressed concern that the over use of antiseptic and antibacterial agents might lead to an increase in dangerous, resistant strains of bacteria. The theory states that this could cause bacteria to evolve to the point where they are no longer harmed by antiseptics.
Different antiseptics differ in how easily bacteria are able to find genetic defenses against particular compounds. It can also be dose dependent; resistance can occur at low doses but not at high; and resistance to one compound can sometimes increase resistance to others.

 

Disinfectant

Disinfectants are antimicrobial agents that are applied to non-living objects to destroy microorganisms, the process of which is known as disinfection. Disinfection is defined as: Cleaning an article of some or all of the pathogenic organisms which may cause infection Disinfectants should generally be distinguished from antibiotics that destroy microorganisms within the body, and from antiseptics, which destroy microorganisms on living tissue. Sanitizers are substances that reduce the number of microorganisms to a safe level. One official and legal definition states that a sanitizer must be capable of killing 99.999%, known as a 5 log reduction, of a specific bacterial test population, and to do so within 30 seconds. The main difference between a sanitizer and a disinfectant is that at a specified use dilution, the disinfectant must have a higher kill capability for pathogenic bacteria compared to that of a sanitizer. Very few disinfectants and sanitizers can sterilize (the complete elimination of all microorganisms), and those that can depend entirely on their mode of application. Bacterial endospores are most resistant to disinfectants; however some viruses and bacteria also possess some tolerance.

Properties

A perfect disinfectant would also offer complete and full sterilization, without harming other forms of life, be inexpensive, and non-corrosive. Unfortunately ideal disinfectants do not exist. Most disinfectants are also, by their very nature, potentially harmful (even toxic) to humans or animals. They should be treated with appropriate care. Most come with safety instructions printed on the packaging, which should be read in full before using the disinfectant. Most modern household disinfectants contain Bitrex, an exceptionally bitter substance designed to discourage ingestion, as an added safety measure. Those that are used indoors should never be mixed with other cleaning products as chemical reactions can occur. They are frequently used in hospitals, dental surgeries, kitchens and bathrooms to kill infectious organisms.
The choice of the disinfectant to be used depends on the particular situation. Some disinfectants have a wide spectrum (kill nearly all microorganisms), while others kill a smaller range of disease-causing organisms but are preferred for other properties (they may be non-corrosive, non-toxic, or inexpensive).
The disinfecting properties of ultra-violet light (a component of sunlight) are powerful. Rather than total reliance on chemicals, basic hygiene—a pillar of food safety—is important in the effort to control bacteria since they generally prefer a warm-moist-dark environment. There are arguments for creating or maintaining conditions which are not conducive to bacterial survival and multiplication, rather than attempting to kill them with chemicals. Bacteria have a very rapid multiplication rate, which enables them to evolve rapidly. Should some bacteria survive a chemical attack, they give rise to the next generation. Thus they are able to develop resistance to hostile chemicals. For this reason, some question the wisdom of impregnating cloths, cutting boards and worktops in the home with bactericidal chemicals.

Types of disinfectants

Alcohols

Alcohols, usually ethanol or isopropanol, are sometimes used as a disinfectant, but more often as an antiseptic (the distinction being that alcohol tends to be used on living tissue rather than nonliving surfaces). They are non-corrosive, but can be a fire hazard. They also have limited residual activity due to evaporation, which results in brief contact times unless the surface is submerged, and have a limited activity in the presence of organic material. Alcohols are most effective when combined with purified water to facilitate diffusion through the cell membrane; 100% alcohol typically denatures only external membrane proteins. A mixture of 70% ethanol or isopropanol diluted in water is effective against a wide spectrum of bacteria, though higher concentrations are often needed to disinfect wet surfaces. Additionally, high-concentration mixtures (such as 80% ethanol + 5% isopropanol) are required to effectively inactivate lipid-enveloped viruses (such as HIV, hepatitis B, and hepatitis C). Alcohol is, at best, only partly effective against most non-enveloped viruses (such as hepatitis A), and is not effective against fungal and bacterial spores.

Aldehyde

Aldehydes, such as glutaraldehyde, have a wide microbicidal activity and are sporicidal and fungicidal. They are partly inactivated by organic matter and have slight residual activity.

Some bacteria have developed resistance to glutaraldehyde, and it has been found that glutaraldehyde can cause asthma and other health hazards; hence ortho-phthalaldehyde is replacing glutaraldehyde.

Oxidizing agents

Oxidizing agents act by oxidizing the cell membrane of microorganisms, which results in a loss of structure and leads to cell lysis and death. A large number of disinfectants operate in this way. Chlorine and oxygen are strong oxidizers, so their compounds figure heavily here.  

Sodium hypochlorite is very commonly used. Common household bleach is a sodium hypochlorite solution and is used in the home to disinfect drains, toilets, and other surfaces. In more dilute form, it is used in swimming pools, and in still more dilute form, it is used in drinking water. When pools and drinking water are said to be chlorinated, it is actually sodium hypochlorite or a related compound—not pure chlorine—that is being used. Chlorine partly reacts with proteinaceous liquids such as blood to form non-oxidizing N-chloro compounds, and thus higher concentrations much be used if disinfecting surfaces after blood spills.

Other hypochlorites such as calcium hypochlorite are also used, especially as a swimming pool additive. Hypochlorites yield an aqueous solution of hypochlorous acid that is the true disinfectant. Hypobromite solutions are also sometimes used.
Chloramine is often used in drinking water treatment.
Chloramine-T is antibacterial even after the chlorine has been spent.
Chlorine dioxide is used as an advanced disinfectant for drinking water to reduce waterborne diseases. In certain parts of the world, it has largely replaced chlorine because it forms fewer byproducts. Sodium chlorite, sodium chlorate, and potassium chlorate are used as precursors for generating chlorine dioxide.
Hydrogen peroxide is used in hospitals to disinfect surfaces and it is used in solution alone or in combination with other chemicals as a high level disinfectant. Hydrogen peroxide vapor is used as a medical sterilant and as room disinfectant. Hydrogen peroxide has the advantage that it decomposes to form oxygen and water thus leaving no long term residues, but hydrogen peroxide as with most other strong oxidants is hazardous, and solutions are a primary irritant. The vapor is hazardous to the respiratory system and eyes and consequently the OSHA permissible exposure limit is 1 ppm (29 CFR 1910.1000 Table Z-1) calculated as an eight hour time weighted average and the NIOSH immediately dangerous to life and health limit is 75 ppm. Therefore, engineering controls, personal protective equipment, gas monitoring etc. should be employed where high concentrations of hydrogen peroxide are used in the workplace. Hydrogen peroxide is sometimes mixed with colloidal silver. It is often preferred because it causes far fewer allergic reactions than alternative disinfectants. Also used in the food packaging industry to disinfect foil containers. A 3% solution is also used as an antiseptic. However, recent studies have shown hydrogen peroxide to be toxic to growing cells as well as bacteria; its use as an antiseptic is no longer recommended.
Iodine is usually dissolved in an organic solvent or as Lugol's iodine solution. It is used in the poultry industry. It is added to the birds’ drinking water. Although no longer recommended because it increases both scar tissue formation and healing time, tincture of iodine has also been used as an antiseptic for skin cuts and scrapes.
Ozone is a gas that can be added to water for sanitation.
Acidic electrolyzed water is a strong oxidising solution made from the electrolysis of ordinary tap water in the presence of a specific amount of salt, generally sodium chloride. Anolyte has a typical pH range of 3.5 to 8.5 and an Oxidation-Reduction Potential (ORP) of +600 to +1200 mV. The most powerful anolyte disinfecting solution is that produced at a controlled 5.0 to 6.3 pH where the predominant oxchlorine species is hypochlorous acid. This environmentally-responsible disinfectant is highly efficacious against bacteria, fungus, mold, spores and other micro-organisms, in very short contact times. It may be applied as liquid, fog or ice.
Peracetic acid is a disinfectant produced by reacting hydrogen peroxide with acetic acid. It is broadly effective against microorganisms and is not deactivated by catalase and peroxidase, the enzymes that break down hydrogen peroxide. It also breaks down to food safe and environmentally friendly residues (acetic acid and hydrogen peroxide), and therefore can be used in non-rinse applications. It can be used over a wide temperature range (0-40°C), wide pH range (3.0-7.5), in clean-in-place (CIP) processes, in hard water conditions, and is not affected by protein residues.
Lactic acid is a registered disinfectant. Due to its natural and environmental profile, it has gained importance in the market.
Performic acid is the simplest and most powerful perorganic acid. Formed from the reaction of hydrogen peroxide and formic acid, it reacts more rapidly and powerfully than peracetic acid before breaking down to water and carbon dioxide. Performic acid is the ultimate environmentally friendly oxidising biocide for all disinfection applications.
Potassium permanganate (KMnO₄) is a red crystalline powder that colours everything it touches, and is used to disinfect aquariums. It is also used widely in community swimming pools to disinfect ones feet before entering the pool. Typically, a large shallow basin of KMnO₄/water solution is kept near the pool ladder. Participants are required to step in the basin and then go into the pool. Additionally, it is widely used to disinfect community water ponds and wells in tropical countries, as well as to disinfect the mouth before pulling out teeth. It can be applied to wounds in dilute solution; potassium permanganate is a very useful disinfectant.
Potassium peroxymonosulfate, the principal ingredient in Virkon, is a wide-spectrum disinfectant used in labs. Virkon kills bacteria, viruses, and fungi. It is used as a 1% solution in water, and keeps for one week once it is made up. It is expensive, but very effective; its pink colour fades as it is used up so it is possible to see at a glance if it is still fresh.

Phenolics

Phenolics are active ingredients in some household disinfectants. They are also found in some mouthwashes and in disinfectant soap and hand washes.

Phenol is probably the oldest known disinfectant as it was first used by Lister, when it was called carbolic acid. It is rather corrosive to the skin and sometimes toxic to sensitive people.
o-Phenylphenol is often used instead of Phenol, since it is somewhat less corrosive.
Chloroxyphenol is the principal ingredient in Dettol, a household disinfectant and antiseptic.
Hexachlorophene is a phenolic that was once used as a germicidal additive to some household products but was banned due to suspected harmful effects.
Thymol, derived from the herb thyme, is the active ingredient in the only 100% botanical disinfectant with an EPA registration benefit. Registered as "broad spectrum," or hospital-grade, it is also the only disinfectant with a green certification, Environmental Choice. Regardless of its Canadian "green" certification, the active ingredient is dangerous to the environment and toxic to aquatic organisms; and, may cause long term adverse effects in the aquatic environment.

Quaternary ammonium compounds

Quaternary ammonium compounds ("quats"), such as benzalkonium chloride, are a large group of related compounds. Some have been used as low level disinfectants. They are effective against bacteria, but not against some species of Pseudomonas bacteria or bacterial spores. Quats are biocides which also kill algae and are used as an additive in large-scale industrial water systems to minimize undesired biological growth. Quaternary ammonium compounds can also be effective disinfectants against enveloped viruses.

Other

The biguanide polymer polyaminopropyl biguanide is specifically bactericidal at very low concentrations (10 mg/l). It has a unique method of action: the polymer strands are incorporated into the bacterial cell wall, which disrupts the membrane and reduces its permeability, which has a lethal effect to bacteria. It is also known to bind to bacterial DNA, alter its transcription, and cause lethal DNA damage. It has very low toxicity to higher organisms such as human cells, which have more complex and protective membranes.

High-intensity shortwave ultraviolet light can be used for disinfecting smooth surfaces such as dental tools, but not porous materials that are opaque to the light such as wood or foam. Ultraviolet light fixtures are often present in microbiology labs, and are activated only when there are no occupants in a room (e.g., at night).

Common sodium bicarbonate (NaHCO3) has disinfectant properties.

Relative effectiveness of disinfectants

One way to compare disinfectants is to compare how well they do against a known disinfectant and rate them accordingly. Phenol is the standard, and the corresponding rating system is called the "Phenol coefficient". The disinfectant to be tested is compared with phenol on a standard microbe (usually Salmonella typhi or Staphylococcus aureus). Disinfectants that are more effective than phenol have a coefficient > 1. Those that are less effective have a coefficient < 1.


Home disinfectants
By far the most cost-effective home disinfectant is the commonly used chlorine bleach (a 5% solution of Sodium hypochlorite) which is effective against most common pathogens, including such difficult as organisms tuberculosis (mycobacterium tuberculosis), hepatitis B and C, fungi, and antibiotic-resistant strains of staphylococcus and enterococcus. It even has some disinfectant action against parasitic organisms.
Positives are that it kills the widest range of pathogens of any inexpensive disinfectant, is extremely powerful against viruses and bacteria at room temperature, is commonly available and inexpensive, and breaks down quickly into harmless components (primarily table salt and oxygen).

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ANTISEPTIC

SANITIZER (DISINFECTANT)

DISINFECTANT

BLEACHING AGENT