Chlorhexidine (CHX) (commonly known by the

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quanti ...

forms chlorhexidine gluconate and chlorhexidine digluconate (CHG) or chlorhexidine acetate) is a

disinfectant A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than s ...

and

antiseptic An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...

that is used for skin disinfection before surgery and to sterilize surgical instruments. It may be used both to disinfect the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

of the patient and the

hand A hand is a prehensile, multi-fingered appendage located at the end of the forearm or forelimb of primates such as humans, chimpanzees, monkeys, and lemurs. A few other vertebrates such as the koala (which has two opposable thumbs on each " ...

s of the healthcare providers. It is also used for cleaning

wounds A wound is a rapid onset of injury that involves lacerated or punctured skin (an ''open'' wound), or a contusion (a ''closed'' wound) from blunt force trauma or compression. In pathology, a ''wound'' is an acute injury that damages the epider ...

, preventing

dental plaque Dental plaque is a biofilm of microorganisms (mostly bacteria, but also fungi) that grows on surfaces within the mouth. It is a sticky colorless deposit at first, but when it forms tartar, it is often brown or pale yellow. It is commonly found be ...

, treating yeast infections of the mouth, and to keep urinary catheters from blocking. It is used as a

liquid A liquid is a nearly incompressible fluid that conforms to the shape of its container but retains a (nearly) constant volume independent of pressure. As such, it is one of the four fundamental states of matter (the others being solid, gas, an ...

or powder. Side effects may include skin irritation,

teeth A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, te ...

discoloration, and

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermat ...

, although the risk appears to be the same as other topical antiseptics. It may cause eye problems if direct contact occurs. Use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

appears to be safe. Chlorhexidine may come mixed in

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

, water, or surfactant solution. It is effective against a range of

microorganisms A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...

, but does not inactivate

spores In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, ...

. Chlorhexidine came into medical use in the 1950s. Chlorhexidine is available over the counter (OTC) in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., federal district, five ma ...

. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. In 2020, it was the 273rd most commonly prescribed medication in the United States, with more than 1million prescriptions.

Uses

Chlorhexidine is used in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eye drops, active substance in wound dressings and antiseptic mouthwashes). A 2019

Cochrane review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profes ...

concluded that based on very low certainty evidence in those who are critically ill "it is not clear whether bathing with chlorhexidine reduces hospital‐acquired infections, mortality, or length of stay in the ICU, or whether the use of chlorhexidine results in more skin reactions." In

endodontics Endodontics (from the Greek roots ''endo-'' "inside" and ''odont-'' "tooth") is the dental specialty concerned with the study and treatment of the dental pulp. Overview Endodontics encompasses the study (practice) of the basic and clinical ...

, chlorhexidine has been used for root canal irrigation and as an intracanal dressing but has been replaced by the use of sodium hypochlorite bleach in much of the developed world.

Antiseptic

CHG is active against

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bac ...

and

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

organisms, facultative anaerobes, aerobes, and yeasts. It is particularly effective against Gram-positive bacteria (in concentrations ≥ 1 μg/L). Significantly higher concentrations (10 to more than 73 μg/mL) are required for Gram-negative bacteria and fungi. Chlorhexidine is ineffective against polioviruses and adenoviruses. The effectiveness against herpes viruses has not yet been established unequivocally. There is strong evidence that chlorhexidine is more effective than

povidone-iodine Povidone-iodine (PVP-I), also known as iodopovidone, is an antiseptic used for skin disinfection before and after surgery. It may be used both to disinfect the hands of healthcare providers and the skin of the person they are caring for. It may ...

for clean surgery. Evidence shows that it is the most effective antiseptic for upper limb surgery, and there is no data to suggest that alcoholic chlorhexidine increases the risk of tourniquet-related burns, ignition fires or allergic episodes during surgery. Chlorhexidine, like other cation-active compounds, remains on the skin. It is frequently combined with alcohols (ethanol and isopropyl alcohol).

Dental use

Use of a CHG-based mouthwash in combination with normal tooth care can help reduce the build-up of plaque and improve mild gingivitis. There is not enough evidence to determine the effect in moderate to severe gingivitis. About 20 mL twice a day of concentrations of 0.1% to 0.2% is recommended for mouth-rinse solutions with a duration of at least 30 seconds. Such mouthwash also has a number of

adverse effect An adverse effect is an undesired harmful effect resulting from a Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...

s including damage to the mouth lining, tooth discoloration,

tartar Tartar may refer to: Places * Tartar (river), a river in Azerbaijan * Tartar, Switzerland, a village in the Grisons * Tərtər, capital of Tartar District, Azerbaijan * Tartar District, Azerbaijan * Tartar Island, South Shetland Islands, Ant ...

build-up, and impaired taste. Extrinsic tooth staining occurs when chlorhexidine rinse has been used for 4 weeks or longer. Mouthwashes containing chlorhexidine which stain teeth less than the classic solution have been developed, many of which contain chelated

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic t ...

. Using chlorhexidine as a supplement to everyday mechanical oral hygiene procedures for 4 to 6 weeks and 6 months leads to a moderate reduction in gingivitis compared to placebo, control or mechanical oral hygiene alone. Chlorhexidine is a cation which interacts with

anionic An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

components of

toothpaste Toothpaste is a paste or gel dentifrice used with a toothbrush to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it is an abrasive that aids in removing dental plaque and food from the teeth ...

, such as

sodium lauryl sulfate Sodium dodecyl sulfate (SDS) or sodium lauryl sulfate (SLS), sometimes written sodium laurilsulfate, is an organic compound with the formula . It is an anionic surfactant used in many cleaning and hygiene products. This compound is the sodium sal ...

and sodium monofluorophosphate, and forms salts of low solubility and antibacterial activity. Hence, to enhance the antiplaque effect of chlorhexidine, "it seems best that the interval between toothbrushing and rinsing with CHX hlorhexidinebe more than 30 minutes, cautiously close to 2 hours after brushing".

Topical

Chlorhexidine gluconate is used as a skin cleanser for surgical scrubs, as a cleanser for skin wounds, for preoperative skin preparation, and for germicidal hand rinses. Chlorhexidine

eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline an ...

s have been used as a treatment for eyes affected by ''Acanthamoeba'' keratitis. Chlorhexidine is very effective for poor countries like Nepal and its use is growing in the world for treating the umbilical cord. A 2015

has yielded high-quality evidence that within the community setting, chlorhexidine skin or cord care can reduce the incidence of omphalitis (inflammation of the

umbilical cord In placental mammals, the umbilical cord (also called the navel string, birth cord or ''funiculus umbilicalis'') is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord is physiolog ...

) by 50% and neonatal mortality by 12%.

Side effects

CHG is ototoxic; if put into an ear canal which has a ruptured eardrum, it can lead to deafness. CHG does not meet current European specifications for a hand disinfectant. Under the test conditions of the European Standard EN 1499, no significant difference in the efficacy was found between a 4% solution of chlorhexidine digluconate and soap. In the U.S., between 2007 and 2009, Hunter Holmes McGuire Veterans Administration Medical Center conducted a cluster-randomized trial and concluded that daily bathing of patients in intensive care units with washcloths saturated with chlorhexidine gluconate reduced the risk of hospital-acquired infections. Whether prolonged exposure over many years may have carcinogenic potential is still not clear. The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

recommendation is to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months. When ingested, CHG is poorly absorbed in the gastrointestinal tract and can cause stomach irritation or nausea. If aspirated into the lungs at high enough concentration, as reported in one case, it can be fatal due to the high risk of

acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin col ...

Mechanism of action

At physiologic pH, chlorhexidine salts dissociate and release the positively charged chlorhexidine

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

. The bactericidal effect is a result of the binding of this cationic molecule to negatively charged bacterial cell walls. At low concentrations of chlorhexidine, this results in a bacteriostatic effect; at high concentrations, membrane disruption results in cell death.

Chemistry

It is a cationic polybiguanide ( bisbiguanide). It is used primarily as its salts (e.g., the dihydrochloride, diacetate, and digluconate).

Deactivation

Chlorhexidine is deactivated by forming insoluble salts with

compounds, including the anionic surfactants commonly used as detergents in toothpastes and mouthwashes, anionic thickeners such as carbomer, and anionic emulsifiers such as acrylates/C10-30 alkyl acrylate crosspolymer, among many others. For this reason, chlorhexidine mouth rinses should be used at least 30 minutes after other dental products. For best effectiveness, food, drink, smoking, and mouth rinses should be avoided for at least one hour after use. Many topical skin products, cleansers, and hand sanitizers should also be avoided to prevent deactivation when chlorhexidine (as a topical by itself or as a residue from a cleanser) is meant to remain on the skin.

Synthesis

The structure is based on two molecules of

proguanil Proguanil, also known as chlorguanide and chloroguanide, is a medication used to treat and prevent malaria. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resistan ...

, linked with a hexamethylenediamine spacer. Chlorhexidine synthesis

Brands

Chlorhexidine topical is sold as Betasept, Biopatch, Calgon Vesta, ChloraPrep One-Step, Dyna-Hex, Hibiclens, Hibistat Towelette, Scrub Care Exidine, Spectrum-4 among others. Chlorhexidine gluconate mouthwash is sold as Dentohexin, Paroex, Peridex, PerioChip, Corsodyl and Periogard, among others. Hexoralettene N contains

benzocaine Benzocaine, sold under the brand name Orajel amongst others, is an ester local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as produ ...

menthol Menthol is an organic compound, more specifically a monoterpenoid, made synthetically or obtained from the oils of corn mint, peppermint, or other mints. It is a waxy, clear or white crystalline substance, which is solid at room temperature and ...

and chlorhexidine hydrochloride. It is used as oral antiseptic candies.

Veterinary medicine

In animals, chlorhexidine is used for topical disinfection of wounds, and to manage skin infections. Chlorhexidine-based disinfectant products are used in the dairy farming industry. Post-surgical respiratory problems have been associated with the use of chlorhexidine products in cats.

References

External links

* {{Portal bar, Medicine Antiseptics Biguanides Chloroarenes Disinfectants Oral hygiene Otologicals World Health Organization essential medicines Wikipedia medicine articles ready to translate