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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 quant ...
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 Skin disinfection is a process that involves the application of a disinfectant to reduce levels of microorganisms on the skin. Disinfecting both the skin of the patient and the hands of the healthcare providers are an important part of surgery. S ...
before surgery and to sterilize
surgical instruments A surgical instrument is a tool or device for performing specific actions or carrying out desired effects during a surgery or operation, such as modifying biological tissue, or to provide access for viewing it. Over time, many different kinds of ...
. 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 animal coverings, such as the arthropod exoskeleton, have different ...
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 "h ...
s of the healthcare providers. It is also used for cleaning wounds, 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 Oral candidiasis, also known as oral thrush among other names, is candidiasis that occurs in the mouth. That is, oral candidiasis is a mycosis (yeast/fungal infection) of ''Candida'' species on the mucous membranes of the mouth. ''Candida albic ...
, and to keep
urinary catheters In urinary catheterization a latex, polyurethane, or silicone tube known as a urinary catheter is inserted into the bladder through the urethra to allow urine to drain from the bladder for collection. It may also be used to inject liquids used ...
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, ...
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, ...
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 derm ...
, 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 Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foamin ...
. 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 Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
(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 Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...
. 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 professi ...
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 clinic ...
, chlorhexidine has been used for root canal irrigation and as an intracanal dressing but has been replaced by the use of
sodium hypochlorite Sodium hypochlorite (commonly known in a dilute solution as bleach) is an inorganic chemical compound with the formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may also be viewed as the sodium s ...
bleach Bleach is the generic name for any chemical product that is used industrially or domestically to remove color (whitening) from a fabric or fiber or to clean or to remove stains in a process called bleaching. It often refers specifically, to ...
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 bact ...
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 A facultative anaerobic organism is an organism that makes ATP by aerobic respiration if oxygen is present, but is capable of switching to fermentation if oxygen is absent. Some examples of facultatively anaerobic bacteria are ''Staphylococcus' ...
, 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 A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species ''Enterovirus C'', in the family of ''Picornaviridae''. There are three poliovirus serotypes: types 1, 2, and 3. Poliovirus is composed of an ...
and
adenoviruses Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...
. 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 Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pa ...
. 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 Gingivitis is a non-destructive disease that causes inflammation of the gums. The most common form of gingivitis, and the most common form of periodontal disease overall, is in response to bacterial biofilms (also called plaque) that is attac ...
. 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 medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term compl ...
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, A ...
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 Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are ...
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 periodi ...
. 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 conven ...
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 s ...
and
sodium monofluorophosphate Sodium monofluorophosphate, commonly abbreviated SMFP, is an inorganic compound with the chemical formula Na2PO3F. Typical for a salt, MFP is odourless, colourless, and water-soluble. This salt is an ingredient in some toothpastes.Klaus Schrödter ...
, 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 ...
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
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 professi ...
has yielded high-quality evidence that within the community setting, chlorhexidine skin or cord care can reduce the incidence of
omphalitis Omphalitis of newborn is the medical term for inflammation of the umbilical cord stump in the neonatal newborn period, most commonly attributed to a bacterial infection. Typically immediately after an infant is born, the umbilical cord is cut wi ...
(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 physiologi ...
) 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 Hunter Holmes McGuire Veterans Administration Medical Center, also known as Richmond VA Medical Center or McGuire VA Hospital, is located in Richmond, Virginia. History The facility is named in honor of Hunter Holmes McGuire, M.D. (1835–19 ...
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 colo ...
.


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 conven ...
. 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 A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfect ...
effect; at high concentrations, membrane disruption results in cell death.


Chemistry

It is a cationic polybiguanide (
bisbiguanide Bisbiguanides are a class of chemically related compounds known for their bactericidal properties. Generally considered to be of the generic formula: R1 R2 N.C(:NR6)NH.C(:NH)NH.CH2 X--(CH2)3 NH.C(:NH)NH.C(:NR7)NR3 R4 V. These compounds include the ...
). It is used primarily as its salts (e.g., the dihydrochloride, diacetate, and digluconate).


Deactivation

Chlorhexidine is deactivated by forming insoluble salts 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 conven ...
compounds, including the anionic
surfactants Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming ...
commonly used as detergents in toothpastes and mouthwashes, anionic thickeners such as carbomer, and anionic
emulsifiers An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Although ...
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 resista ...
, linked with a hexamethylenediamine spacer.


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 products ...
,
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 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.


See also

* Polyaminopropyl biguanide * Polyhexanide *
Triclosan Triclosan (sometimes abbreviated as TCS) is an antibacterial and antifungal agent present in some consumer products, including toothpaste, soaps, detergents, toys, and surgical cleaning treatments. It is similar in its uses and mechanism of act ...


References


External links

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