CAS: 55-56-1
IUPAC Name: (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine
Molecular Formula: C22H30Cl2N10
Molecular Weight: 505.4
Chlorhexidine (CHX) (commonly known by the salt forms chlorhexidine gluconate and chlorhexidine digluconate (CHG) or chlorhexidine acetate) is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surgical instruments.
Chlorhexidinemay be used both to disinfect the skin of the patient and the hands of the healthcare providers.
Chlorhexidineis also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and to keep urinary catheters from blocking.
Chlorhexidineis used as a liquid or powder.
Chlorhexidine came into medical use in the 1950s.
Chlorhexidine is available over the counter (OTC) in the United States.
Chlorhexidineis on the World Health Organization's List of Essential Medicines.
In 2017, Chlorhexidine was the 286th most commonly prescribed medication in the United States, with more than one million prescriptions.
The name "chlorhexidine" breaks down as chlor(o) + hex(ane) + id(e) + (am)ine.
Uses of Chlorhexidine:
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 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In endodontics, chlorhexidine is used for root canal irrigation and as an intracanal dressing, but has been replaced by the use of sodium hypochlorite bleach in much of the developed world.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 and Gram-negative organisms, facultative anaerobes, aerobes, and yeasts.
Chlorhexidineis 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 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.
Chlorhexidineis frequently combined with alcohols (ethanol and isopropyl alcohol).
Dental uses of Chlorhexidine:
Perichlor brand 0.12% chlorhexidine gluconate solution
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 effects including damage to the mouth lining, tooth discoloration, tartar 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.
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 components of toothpaste, such as sodium lauryl sulfate 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 [chlorhexidine] be 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 drops 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 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) by 50% and neonatal mortality by 12%.
Mechanism of action:
At physiologic pH, chlorhexidine salts dissociate and release the positively charged chlorhexidine cation.
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 of Chlorhexidine:
Chlorhexidineis a cationic polybiguanide (bisbiguanide).
Chlorhexidineis used primarily as its salts (e.g., the dihydrochloride, diacetate, and digluconate).
Deactivation:
Chlorhexidine is deactivated by forming insoluble salts with anionic 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.
Chlorhexidine is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surgical instruments.
KEYWORDS:
55-56-1, Rotersept, Fimeil, Hexadol, Soretol, Chlorhexidin, Chlorhexidinum, Nolvasan, Hibistat, 16-Bis(p-chlorophenyldiguanido)hexane
Properties of Chlorhexidine:
Melting Point: 154.5 °C
Solubility: 800 mg/L (at 20 °C)
XLogP3: 0.1
Hydrogen Bond Donor Count: 6
Hydrogen Bond Acceptor Count: 2
Rotatable Bond Count: 13
Exact Mass: 504.2031964
Monoisotopic Mass: 504.2031964
Topological Polar Surface Area: 178 Ų
Heavy Atom Count: 34
Complexity: 649
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 2
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes
Chlorhexidine is an antiseptic and disinfectant.
Chlorhexidinehelps reduce the number of germs (bacteria) in your mouth or on your skin.
Chlorhexidinecan help with:
-mouth infections, mouth ulcers and gum disease
-sore throats
-denture care
-skin infections
Chlorhexidine is usually combined with other ingredients.
Some sore throat treatments have a local anaesthetic to help numb pain.
Mouth and throat treatments come as mouthwashes, lozenges, gels and sprays.
Skin treatments come as creams, ointments and lotions.
Many chlorhexidine treatments are available to buy in pharmacies, and some in shops and supermarkets.
For nose infections, there is a nasal cream that contains chlorhexidine and neomycin, an antibiotic.
This medicine is available on prescription only and is known by the brand name Naseptin.
Chlorhexidine is also used in hospitals and clinics to clean skin or surgical equipment before surgery.
Chlorhexidinecan be used in some bladder procedures, including cleaning catheters.
Key facts of Chlorhexidine:
You’ll usually use chlorhexidine treatments for up to 4 weeks.
You’re unlikely to have any side effects with the skin creams and lotions.
Common side effects with the throat spray, lozenges and dental treatments include a dry mouth and stained teeth.
When using the lozenges, spray, mouthwash or dental gel, wait at least 30 to 60 minutes before having something to eat or drink.
This gives the medicine a chance to work properly.
Do not use bleach on clothes, bedding or other fabrics that have been in contact with chlorhexidine.
Chlorhexidinewill leave yellowish-brown stains.
Who can and cannot use chlorhexidine?
Chlorhexidine throat spray, lozenges and dental treatments (including mouthwash and dental gel) can be used by adults and children aged 12 or older.
Chlorhexidine skin treatments can be used by adults and children.
To make sure chlorhexidine is safe for you, tell a pharmacist or doctor before using it if you:
have ever had an allergic reaction to chlorhexidine or any of the other ingredients
have ever had an allergic reaction to any other medicine
cannot drink or need to avoid alcohol. Some chlorhexidine sprays and mouthwashes may contain very small amounts of alcohol.
Ask a pharmacist, doctor or dentist about medicines without alcohol.
How and when to use chlorhexidine?
If you buy a chlorhexidine treatment in a pharmacy or supermarket, follow the instructions that come with it.
For prescription medicines, follow the advice from your doctor, dentist or a pharmacist.
Wash your hands before and after using chlorhexidine. Keep it away from your eyes and ears.
If chlorhexidine gets into your eyes or ears, rinse well with water.
Dosage and how to use lozenges:
The usual dose for children aged 12 and older is up to 5 lozenges a day.
Adults can have up to 10 a day.
Put a lozenge in your mouth and let it melt slowly.
Wait at least 30 to 60 minutes before having something to eat or drink.
Dosage and how to use mouthwash
The usual dose is 10 ml, twice a day.
Pour 10ml into the measuring cup. Rinse the mouthwash around your mouth for about 1 minute.
Spit out the mouthwash, do not swallow it.
Wait at least 30 to 60 minutes before having something to eat or drink.
Dosage and how to use mouth spray
The usual dose is 2 squirts at a time, up to 12 times a day.
Aim the spray onto your affected tooth, gum, ulcer or the sore part of your mouth.
Wait at least 30 to 60 minutes before having something to eat or drink.
Dosage and how to use throat spray
The usual dose is 3 to 5 squirts. You can repeat this dose up to 10 times a day.
Wait at least 30 to 60 minutes before having something to eat or drink.
How to use dental gel:
You’ll usually use the gel once or twice a day.
Put a small amount of gel onto your fingertip or a cotton bud.
Gently wipe it across the surface of your mouth ulcer, gum or the sore part of your mouth.
Wait at least 30 to 60 minutes before having something to eat or drink.
How to use sore throat treatments
Only use chlorhexidine lozenges and sore throat spray for a short time.
Do not keep using them continuously.
Contact a doctor if your symptoms do not improve after 3 to 4 days.
How to use dental treatments
Use your dental treatment at a different time of day to when you brush your teeth.
This is because toothpaste can stop chlorhexidine working properly.
If you cannot use it at a different time, then rinse your mouth thoroughly with water after brushing your teeth.
Wait at least 5 minutes before using chlorhexidine.
If your symptoms do not improve after one week, or if they get worse at any time, stop using chlorhexidine and contact your dentist or doctor.
Check with your dentist, doctor or pharmacist if you’re not sure how long to use it for.
Chlorhexidine skin treatments:
Keep chlorhexidine skin treatments away from your eyes and mouth.
Skin treatments are usually used short-term for a few weeks, but occasionally you may have to use them for longer.
You can use treatments like Dermol lotion as both a body wash (soap substitute) and moisturising skin lotion.
How to use skin cream or lotion:
Apply a thin layer of chlorhexidine cream or lotion to the affected areas of your skin. Follow the directions included in the packet.
How to use chlorhexidine as soap substitute or wash
Use your chlorhexidine treatment instead of soap or shower gel when you wash.
You use Chlorhexidine in the same way as an ordinary soap or gel.
However, Chlorhexidine may not be as foamy.
Be careful not to slip in the bath or shower, or on a tiled floor, when using the cream or lotion.
If you are going into hospital, you may be sent a chlorhexidine product to wash with before you come into hospital to reduce the chances of infection.
This should come with instructions on how to use it.
What if I forget to use my chlorhexidine treatment?
If you forget your chlorhexidine dental or sore throat treatment, use it as soon as you remember, unless it's nearly time for your next dose.
In this case, just skip the missed dose and have your next one as normal.
If you forget to use your chlorhexidine skin treatment, that’s okay.
Just start your routine again after the missed treatment and carry on as before.
If you have been prescribed chlorhexidine and forget to take it or apply it on a regular basis, it may help to set an alarm to remind you.
You could also ask your pharmacist for other ways to remember your medicine.
What if I use Chlorhexidine too much?
Chlorhexidine is usually a safe medicine if you follow the instructions that come with it.
However, do not use more than the recommended dose.
Speak to your doctor or a pharmacist now if you or your child has swallowed too much.
How to use Chlorhexidine Gluconate Mouthwash
Rinse your mouth with the solution after brushing your teeth, usually twice daily (after breakfast and at bedtime) or as directed by your doctor.
Measure 1/2 ounce (15 milliliters) of the solution using the supplied measuring cup.
Swish the solution in your mouth for 30 seconds, and then spit it out.
Do not swallow the solution or mix it with any other substance.
After using chlorhexidine, wait at least 30 minutes before rinsing your mouth with water or mouthwash, brushing your teeth, eating, or drinking.
Dosage is based on your medical condition and response to treatment.
Use this medication regularly to get the most benefit from it.
To help you remember, use it at the same times each day.
Chlorhexidinemay take up to 6 weeks to see the full benefits of using this medication.
Tell your doctor if your condition lasts or gets worse.
Chlorhexidine is an antiseptic mainly used in dental medicines like mouth rinses, sprays or toothpaste to prevent plaque and gingivitis.
Chlorhexidine is also used on plasters, in ointments or powders and as an effective preservative against bacteria and moulds in cosmetics.
Chlorhexidine is a broad-spectrum antimicrobial biguanide used as a topical antiseptic and in dental practice for the treatment of inflammatory dental conditions caused by microorganisms.
Chlorhexidineis one of the most common skin and mucous membrane antiseptic agents in use today.
The molecule itself is a cationic bis-guanide consisting of two 4-chlorophenyl rings and two biguanide groups joined by a central hexamethylene chain.
Topical chlorhexidine for disinfection, as well as oral rinses for dental use, carries activity against a broad range of pathogens including bacteria, yeasts, and viruses.
Chlorhexidine is available over-the-counter in various formulations (e.g. solution, sponge, cloth, swab) as a topical antiseptic to sanitize prior to surgeries and/or medical procedures.
Dental formulations, available by prescription only, include an oral rinse indicated for the treatment of gingivitis11 and a slow-release "chip" which is inserted into periodontal pockets and is indicated for the reduction of pocket depth in adult patients with periodontitis as an adjunct therapy to dental scaling and root planing procedures.
Chlorhexidine is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses.
Antimicrobial activity is dose-dependent - chlorhexidine is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%).
Pharmacokinetic studies of oral chlorhexidine rinses indicate that approximately 30% of the active ingredient is retained in the mouth following rinsing, which is subsequently slowly released into oral fluids.
This ability to adsorb to dentine, shared with tetracycline antibiotics such as doxycycline, is known as "substantivity" and is the result of chlorhexidine's positive charge.
Chlorhexidineis likely that this substantivity plays at least some role in chlorhexidine's antimicrobial activity, as its persistence on surfaces such as dentine prevent microbial colonization.
Dental chlorhexidine rinses may result in staining of oral surfaces, such as teeth.
This effect is not ubiquitous and appears to be more significant with extended therapy (i.e. up to 6 months) - nevertheless, patients for whom oral staining is unacceptable should use chlorhexidine rinse with caution and for the shortest effective interval.
Allergic reactions to chlorhexidine have been associated with the development of anaphylaxis.
Chlorhexidine’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes.
The positively charged chlorhexidine molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows chlorhexidine to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death.
The specific means of cell death is dependent on the concentration of chlorhexidine - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.
Chlorhexidine is the most commonly used mouthwash for chemical plaque control.
Chlorhexidineis use is becoming widespread as an adjuvant treatment of mechanical control, particularly in individuals with compromised oral hygiene.
However, several adverse effects that limit patients’ acceptance of mouth rinsing have been identified—brown staining of the teeth, an unpleasant taste, and rarely painful desquamation of the oral mucosa.
Alternative formulations of chlorhexidine and other chemical plaque controls have therefore been developed to minimize adverse effects.
Desquamation and ulceration of the oral mucosa after the use of chlorhexidine mouthwashes.
Must be very infrequence.
Histological and histochemical examination of mucosal biopsies taken after 18 months of daily exposure to chlorhexidine did not show any adverse effect on the oral mucosa.
There was increased keratinization of human gingival cells in vitro in cell cultures if the chlorhexidine concentration exceeded 25 μg/ml, and the same acceleration of keratinization of human gingival cells in gingival swabs occurred after rinsing with 0.025%, 0.05%, and 0.1% chlorhexidine solutions.
In one case there was excessive impairment of wound healing after daily rinses with a 0.1% chlorhexidine solution after oral surgery.
Staining of the teeth was the first and principal adverse effect observed with the dental use of chlorhexidine.
In a 4-month study of soldiers who used chlorhexidine mouthwashes in concentrations of 0.1% and 0.2%, 15% of the interproximal surface and 62% of the fillings, especially the old and porous ones, were discolored [35,36].
The stain intensity seems to be directly correlated to the concentration of the chlorhexidine and to the frequency and duration of use.
The type of administration (0.2% mouthwash, 0.2% spray, or 1% gel) does not seem to influence the amount of tooth-staining.
The initial discoloration is yellow-brown, but prolonged use and stronger concentrations result in a dark-brown color.
Extensive investigations have been performed to evaluate factors that influence tooth-staining and the possibility of avoiding it.
The cause of extrinsic tooth discoloration is not fully understood.
However, the available evidence suggests that browning and formation of pigmented metal sulfides are the most likely causes, while dietary factors (such as beverages or red wine) and smoking may play an aggravating role only.
A discoloration of the dorsum of the tongue occurs in up to one-third of subjects using chlorhexidine mouth rinses.
Chlorhexidinedoes not occur during the use of chlorhexidine-containing dentifrices or gels.
The effects of three oral sprays containing chlorhexidine, benzydamine hydrochloride, and chlorhexidine plus benzydamine hydrochloride on plaque and gingivitis have been compared. Chlorhexidine and chlorhexidine + benzydamine hydrochloride sprays were equally effective and the benzydamine hydrochloride spray alone was less effective.
The chlorhexidine/benzydamine hydrochloride spray caused a burning sensation.
Chlorhexidine has been used extensively for many decades as a broad-spectrum antiseptic in hospitals and elsewhere.
Chlorhexidinehas also been given as a maternal vaginal lavage, full-body newborn skin cleanser, and for umbilical cord cleansing to prevent infection in neonates.
Recent evidence has suggested that these chlorhexidine interventions may have a significant effect on the burden of neonatal infection and mortality in developing countries.
Of the 4 million annual neonatal deaths that occur globally, more than 99% occur in developing countries, and about 36% are attributed to infections.
The potential of chlorhexidine vaginal cleansing to reduce vertical transmission of HIV has been examined in developing countries; the use of a 1% chlorhexidine concentration has been recommended.
Chlorhexidine interventions have been shown to have the potential to reduce maternal and neonatal mortality and morbidity significantly in low-resource settings, although data on safety were incomplete.
A further review of the research available has shown that despite positive results the use of chlorhexidine to prevent perinatal mortality and morbidity has not been widely adopted.
In the transition from chlorhexidine research to public health implementation in developing countries, the authors suggested that high priority be given to evaluation whether further evidence is needed to demonstrate safety and effectiveness, and to determine how evidence should be obtained.
Chlorhexidine is a widely used skin antisepsis preparation and is an ingredient in toothpaste and mouthwash.
Chlorhexidineis an especially effective antiseptic when combined with alcohol.
Its antimicrobial effects persist because it is binds strongly to proteins in the skin and mucosa, making it an effective antiseptic ingredient for handwashing, skin preparation for surgery and the placement of intravascular access.
Catheters impregnated with chlorhexidine and
antimicrobial agents can reduce the incidence of catheter-related bloodstream infections. Contact dermatitis related to chlorhexidine is not common in health care workers.
The incidence of contact dermatitis to chlorhexidine in atopic patients is approximately 2.5 to 5.4%.
Acute hypersensitivity reactions to chlorhexidine are often not recognised and therefore may be underreported.
This review discusses the pharmacology, microbiology, clinical applications and adverse effects of chlorhexidine.
Chlorhexidine was developed as an antiseptic agent by Imperial Chemical Industries, (Manchester, UK) in the 1950s1.
Chlorhexidine is used widely as an antiseptic agent in medical practice and is an ingredient in personal hygiene items such as mouthwash and toothpaste.
The aims of this review are to summarise the pharmacology, clinical uses and adverse effects of chlorhexidine.
CHEMISTRY of Chlorhexidine:
Chlorhexidine (1:6-di[4-chlorophenyldiguanido]- hexane) is a bisbiguanide that consists of two chlorguanide chains linked by a hexamethylene chain.
Chlorhexidineis a strong base and is a di-cation at physiological pH.
Chlorhexidine is insoluble in water and is formulated with either gluconic or acetic acid to form water soluble digluconate or diacetate salts.
Chlorhexidine solutions are colourless, odourless and have an extremely bitter taste.
When used topically, the N-chlorinated derivative of chlorhexidine binds covalently to proteins in the skin and mucosa and results in a persisting antimicrobial effect with limited systemic absorption, even after an oral ingestion.
MECHANISM OF ACTION:
Chlorhexidine is adsorbed onto phosphatecontaining protein components in the bacterial cell wall.
At bacteriostatic concentrations, Chlorhexidine penetrates and disrupts the bacterial cytoplasmic membrane resulting in leakage of cytoplasmic components.
At higher concentrations Chlorhexidine exerts a bactericidal action by forming irreversible precipitates with intracellular adenosine triphosphate and nucleic acids after entering the cytoplasm via the damaged cytoplasmic membrane.
Chlorhexidine has bacteriostatic, bactericidal, fungicidal, fungistatic and some virus killing properties.
Minimum inhibitory concentrations are lower for Gram-positive bacteria than for Gramnegative bacteria because chlorhexidine has an increased affinity for the cell wall of Gram-positive organisms.
Prolonged exposure increases the bactericidal effect for most bacteria.
Chlorhexidine has minimal activity against acid fast bacilli or heat resistant bacterial spores.
In contrast with povidone iodine, the antimicrobial activity of chlorhexidine is not affected by the presence of body fluids such as blood.
Chlorhexidine, an antiseptic solution that has been used worldwide since the 1950s, is a safe and effective product with broad antiseptic activity.
Novel uses of chlorhexidine-containing products are being implemented to promote antisepsis and prevent bacterial colonization and infection.
We review some of the many infection control applications of chlorhexidine in the battle against HAI, such as general skin cleansing, skin decolonization, preoperative showering and bathing, vascular catheter site preparation, impregnated catheter site dressings, impregnated catheters, and oral decontamination.
As mandatory public reporting and pay for performance force infection control issues to the forefront, chlorhexidine-containing products may provide a vast armamentarium for the control and prevention of HAI.
Health care-associated infections (HAIs), the most common adverse events encountered by hospitalized patients, complicate the hospital course of up to 10% of people who are admitted to acute care hospitals.
These often serious infections result in significantly increased patient morbidity, mortality, length of stay, and utilization of health care resources.
As health care technology advances, ironically, so do rates of HAI.
Novel uses of experienced products are being implemented to combat these challenging infections.
Here, we review decades of experience with an increasingly popular antiseptic, chlorhexidine.
In this review, we focus on applications of chlorhexidine as an infection control tool to prevent HAI and present evidence for the use of chlorhexidine to decontaminate both people and devices.
In addition, we address safety concerns, such as development of drug resistance and adverse drug reactions.
Additional areas of needed research are addressed, highlighting high-risk populations that may benefit from chlorhexidine interventions but for whom data are currently lacking.
Chlorhexidine is a topical antiseptic solution that has been used worldwide since 1954.
Chlorhexidineis use in children and adults has provided an excellent record of safety and efficacy for applications as diverse as hand washing, preoperative skin preparation, vaginal antisepsis, treatment of gingivitis, and body washes to prevent neonatal sepsis.
Chlorhexidine gluconate is a water-soluble, cationic biguanide that binds to the negatively charged bacterial cell wall, altering the bacterial cell osmotic equilibrium.
Chlorhexidine is commercially available at a variety of concentrations (0.5%–4%) and formulations (with and without isopropyl alcohol or ethanol), and certain chlorhexidine-containing products are available over the counter.
Because chlorhexidine-containing products come in many formulations and concentrations, we use “chlorhexidine” in this review to encompass chlorhexidine-containing solutions.
At low concentrations, chlorhexidine affects membrane integrity, but at high concentrations, cytoplasmic contents precipitate, resulting in cell death.
Chlorhexidine (0.05% solution) has broad activity against gram-positive and gram-negative bacteria, facultative anaerobes and aerobes, yeasts, and some lipid-enveloped viruses, including HIV.
Chlorhexidine is not sporicidal.
Although decreased susceptibility to chlorhexidine has been reported, it has not been convincingly shown to be associated with repeated exposure to chlorhexidine.
Proposed mechanisms include drug inactivation, efflux, and decreased uptake.
Vancomycin-resistant enterococci (VRE) and vancomycin-susceptible enterococci, for example, have equivalent susceptibilities to chlorhexidine.
Some Pseudomonas species and other nonfermenting Gram-negative organisms have high-level resistance to chlorhexidine.
Plasmid-mediated resistance mechanisms to antiseptics are documented for staphylococci, as are increased MICs; however, the clinical significance of these increased MICs has not been determined, because they are usually far less than the commonly used chlorhexidine concentrations.
Decreased susceptibility and the potential for emergence of resistance exist.
Several laboratory studies have raised concerns that emergence of biocide nonsusceptibility may result in cross-resistance to antibiotics, but data are limited.
As antiseptics become used more broadly, surveillance of clinical isolates should be considered to identify an epidemiologically significant trend toward decreasing antiseptic and antibiotic susceptibility.
Skin Antisepsis:
Hand washing and skin antisepsis are now considered the most important interventions to prevent the spread of pathogens in hospitals.
Use of chlorhexidine-based soaps and scrubs is supported by 25 years of clinical experience.
Chlorhexidine rapidly reduces both skin flora and transient bacteria, such as Gram-negative bacteria.
In the 1970s, hand washing with chlorhexidine was shown to reduce skin flora by 86%–92%.
In addition, chlorhexidine has residual activity on the skin that helps to prevent rapid regrowth of skin organisms and enhances the duration of skin antisepsis.
When surgeons used chlorhexidine hand scrubs, not only was there a greater reduction in the numbers of bacteria on the skin, compared with use of other antiseptic agents, but the bacterial count suppression was also maintained for up to 6 hour.
The spread of methicillin-resistant Staphylococcus aureus (MRSA) and other multidrug-resistant organisms in hospitals has become a major infection prevention and control focus, especially as community-associated MRSA strains have emerged as a cause of HAI.
MRSA is known to colonize the skin and can be detected by skin culture in 8% of healthy adults and 8%–44% of patients admitted to the intensive care unit (ICU).
MRSA, like other hospital-acquired, multidrug-resistant organisms, is presumed to be transmitted from patient to patient in the ICU on the hands of health care workers.
Historically, most infection control measures have focused on asepsis of health care providers and the environment.
Increasingly, however, decolonization and decontamination of colonized patients is being evaluated.
Colonization with MRSA in adult ICU patients is known to increase the likelihood of subsequent MRSA infection.
Whether decolonization is an effective intervention to prevent subsequent infection remains to be shown, and current Centers for Disease Control and Prevention (CDC) guidelines do not recommend routine decolonization as a standard infection prevention intervention.
However, decolonization is often considered for hospitalized patients in units with high colonization pressure, a known risk factor for MRSA transmission in hospitals.
Whole-body washing with chlorhexidine can reduce skin colonization, but eradication of S. aureus colonization has been achieved only in combination with nasal mupirocin, and the addition of doxycycline and rifampin may enhance decolonization efforts in hospitalized patients.
Chlorhexidine has been used to control outbreaks of S. aureus infection.
Several investigators have used chlorhexidine and intranasal mupirocin to effectively decolonize MRSA carriers in ICUs with a high MRSA prevalence.
The combination of intranasal mupirocin and chlorhexidine baths has been shown to reduce the incidence of nosocomial MRSA infection among ICU patients.
Whether chlorhexidine baths alone can reduce MRSA infection remains unknown.
However, recent evidence suggests that decontaminating ICU patients with daily chlorhexidine baths may reduce transmission of other multidrug-resistant organisms and prevent HAI.
Daily bathing of ICU patients with chlorhexidine decreased skin and environmental contamination with VRE and reduced the incidence of VRE acquisition in a comparison of the intervention period with 2 periods of bathing involving baths that did not contain chlorhexidine.
Not only did the intervention lead to decreased colonization of VRE on the skin of patients, but also fewer health care workers' hands were contaminated with VRE.
Evidence is mounting that daily bathing of ICU patients with chlorhexidine may also reduce HAI.
A recent multicenter study evaluated daily bathing of adult ICU patients with chlorhexidine and found a 32% decrease in the acquisition of MRSA colonization (P<.05), a surrogate for health care-associated transmission of MRSA.
VRE acquisition decreased by 30% (P<.01), and the incidence of all bloodstream infections (BSIs) decreased by 21% (P<.05).
This study evaluated a before-and-after intervention, and additional studies will be needed to confirm these promising results.
Although there is growing literature evaluating the use of chlorhexidine baths for patients with recurrent MRSA abscesses and other infections with community-associated MRSA strains, further research is needed in this important area.
Preoperative bathing and surgical site preparation.
Early studies demonstrated the utility of chlorhexidine-based soaps and hand scrubs; a natural extension of use of this agent lies in the field of preoperative baths and skin preparation for surgical patients.
Postoperative surgical site infections (SSIs) are frequently caused by a patient's own skin flora, including those microorganisms that colonize body sites other than the surgical site.
Similar to hand washing with chlorhexidine, chlorhexidine whole-body bathing significantly reduces microbial burden on the skin, and repeated baths lead to a progressive reduction of organisms over time.
Preoperative bathing and scrubbing with chlorhexidine is superior to preoperative bathing and scrubbing with povidone-iodine in reducing skin colonization at the site of surgical incision.
Preoperative baths are widely encouraged in clinical practice.
Although we expect that decreasing general skin contamination in preoperative patients will decrease the number of SSIs, a clear cause-and-effect relationship has not been established to date.
A recent Cochrane systematic review identified randomized, controlled trials of full-body bathing or showering with chlorhexidine, compared with placebo or regular soap, and found no clear evidence that preoperative bathing with chlorhexidine was more effective at reducing surgical site infections.
Some of these studies entailed full-body rinsing after application of chlorhexidine, and this may have impacted chlorhexidine's antiseptic activity, so conclusions about preoperative bathing should be interpreted with caution.
Chlorhexidine- and iodine-containing compounds are frequently used to prepare the skin immediately before surgery because of both agents' utility in reducing skin microorganisms.
After a single application, chlorhexidine achieves greater reduction in skin flora and has longer residual activity than does povidone-iodine.
Chlorhexidine, unlike the iodophors, is active even in the presence of blood or serum proteins.
There is extensive data demonstrating the reduction in skin flora resulting from use of these products, but again, there is no clear comparison demonstrating superiority of either of these products in reducing SSIs.
The benefits of chlorhexidine skin preparation are more evident when used in preparation for central venous catheter (CVC) insertion.
Insertion and Maintenance of Devices
Intravascular catheters are an integral component of 21st century medical care.
The advantages of prolonged and secure venous access are counterbalanced by the added risks of infectious and noninfectious complications.
Historically, in the United States, povidone-iodine has been used to prepare the skin for CVC insertion.
Current data, however, support chlorhexidine as the preferred agent for skin preparation before CVC placement.
The exact mechanism by which chlorhexidine reduces BSIs is unknown.
For short-term catheters, skin organisms that colonize the catheter site are postulated to migrate along the catheter insertion tract and contaminate the catheter tip.
A multicenter study of neonates showed that skin preparation for peripheral intravenous catheter insertion with chlorhexidine reduced catheter colonization by 50%, compared with use of povidone-iodine.
This reduction of catheter colonization is postulated to decreased likelihood of developing a catheter-related BSI.
In 2002, a meta-analysis reviewed 8 studies (involving 4143 catheters) found a 49% rate of reduction (RR, 0.51; 95% CI, 0.27–0.97) in the risk of catheter-related BSIs among patients whose skin was prepared with chlorhexidine.
The 2002 CDC's “Guidelines for the Prevention of Intravascular Catheter-Related Infections” recognized the data supporting use of chlorhexidine for CVC placement and recommended a chlorhexidine-based preparation over tincture of iodine, an iodophor, or 70% alcohol for cutaneous antisepsis before CVC placement.
Chlorhexidine products are also used in the maintenance of indwelling catheters in attempts to prevent infectious complications.
Catheter site colonization is postulated as the main portal of entry for bacteria that travel down the insertion tract and colonize the catheter tip.
To suppress microorganisms around the catheter insertion site, chlorhexidine-impregnated sponges are available that can be placed circumferentially around the catheter.
Early studies compared these sustained-release chlorhexidine dressings with a transparent dressing in 2 university hospital ICUs.
The treatment group had a reduced risk of catheter colonization and a lower rate of catheter-associated BSIs, but these data remain unpublished.
A multicenter trial involving 6 neonatal ICUs evaluated the impact of chlorhexidine-impregnated dressings on BSI rates and catheter colonization; the study revealed that the neonates randomized to receive chlorhexidine-impregnated dressings were less likely to have colonized central catheter tips, compared with neonates whose catheter site care involved either povidone-iodine or 70% alcohol; however, both groups were equally likely to have a BSI.
A study of children who had undergone cardiac surgery revealed a significant reduction in catheter colonization among patients whose CVCs were maintained with a chlorhexidine-impregnated dressing, but again, there was no difference in the rates of BSIs.
The CDC's “Guidelines for the Prevention of Intravascular Catheter-Related Infections” from 2002 made no recommendations regarding the use of chlorhexidine-impregnated dressings to reduce incidence of infection.
Although these data consistently find decreased colonization of CVCs, few published data demonstrate decreases in catheter-associated BSIs to support widespread use of chlorhexidine-impregnated dressing use.
This is a promising area for further research.
Catheters and catheter cuffs can be impregnated or coated with antiseptics or antimicrobial agents.
Coating of catheters with chlorhexidine in combination with silver sulfadiazine has been studied as a novel method to reduce catheter-associated BSIs.
A meta-analysis from 1999 of randomized trials in which chlorhexidine- and silver sulfadiazine-impregnated CVCs were compared with nonimpregnated catheters revealed that use of catheters impregnated on the external lumen reduced the incidence of both catheter colonization and catheter-associated BSI.
A study of second-generation chlorhexidine- and silver sulfadiazine-impregnated CVCs, with coating on both the intra- and extraluminal sides, found decreased rates of catheter colonization, compared with the rates for standard catheters.
This study was not able to demonstrate a reduction in the number of catheter-associated BSIs, because it was underpowered.
Chlorhexidine- and silver sulfadiazine-impregnated catheters are significantly more expensive than standard catheters; therefore, they are currently cost-effective only for select patient populations for whom BSI rates are high despite the use of appropriate infection control practices and insertion techniques.
The cumulative evidence regarding the efficacy of antiseptic-impregnated catheters in decreasing the rate of catheter-associated BSI is promising for high-risk patients, but other infection control interventions may be more cost-effective in areas with low rates of BSI and for low-risk patients.
Decontamination of the Oropharynx
In addition to skin cleansing, chlorhexidine is increasingly being evaluated for decontamination of the oropharynx.
Chlorhexidine products effectively decontaminate the oropharynx and have been used for decades by dentists for controlling gingivitis and periodontitis.
The applications of chlorhexidine in controlling oral infections is beyond the scope of this review, but we will point out that studies that have evaluated oral chlorhexidine rinses to decrease oral flora and prevent oral complications in bone marrow transplant recipients and other patients with malignancies have yielded mixed results.
Ventilator-associated pneumonia is a major cause of morbidity and mortality in patients hospitalized in intensive care units.
Periodontal disease and poor oral hygiene have been correlated with nosocomial pneumonia.
Several investigators have studied the impact of chlorhexidine decontamination of the nasopharynx and oropharynx on prevention of HAI.
These studies have yielded mixed results: some have shown a reduction in the incidence of ventilator-associated pneumonia, and others have shown no impact on rates of ventilator-associated pneumonia.
Segers et al. specifically studied the incidence of HAI among patients undergoing elective cardiothoracic surgery.
In this population, the authors found that perioperative decontamination of the oropharynx and nasopharynx with chlorhexidine was effective at reducing the absolute risk of postoperative HAI.
Patients in the treatment group had fewer lower respiratory tract infections and deep SSIs, but there was no significant reduction noted for the overall rate of SSI.
A recent meta-analysis concluded from the available literature that, overall, chlorhexidine decontamination may reduce the incidence of ventilator-associated pneumonia by 30%.
The authors note that the benefits may be most significant for cardiac surgery patients undergoing coronary bypass grafting when the duration of postoperative intubation is shorter.
The practice of oral decontamination for perioperative patients and ICU patients undergoing ventilation is highly variable.
Questions still remain about cost-effectiveness, long-term safety, and the generalizability of the efficacy reported in the aforementioned studies.
About Chlorhexidine Helpful information:
This substance is registered under the REACH Regulation and is manufactured in and / or imported to the European Economic Area, for intermediate use only.
Chlorhexidine is used at industrial sites and in manufacturing.
Consumer Uses of Chlorhexidine:
ECHA has no public registered data indicating whether or in which chemical products Chlorhexidine might be used.
ECHA has no public registered data on the routes by which Chlorhexidine is most likely to be released to the environment.
Article service life:
ECHA has no public registered data on the routes by which Chlorhexidine is most likely to be released to the environment.
ECHA has no public registered data indicating whether or into which articles Chlorhexidine might have been processed.
Widespread uses by professional workers:
ECHA has no public registered data indicating whether or in which chemical products Chlorhexidine might be used.
ECHA has no public registered data on the types of manufacture using Chlorhexidine.
ECHA has no public registered data on the routes by which Chlorhexidine is most likely to be released to the environment.
Formulation or re-packing:
ECHA has no public registered data indicating whether or in which chemical products Chlorhexidine might be used.
ECHA has no public registered data on the routes by which Chlorhexidine is most likely to be released to the environment.
Uses at industrial sites:
Chlorhexidine is used in the following products: pharmaceuticals.
Chlorhexidine has an industrial use resulting in manufacture of another substance (use of intermediates).
Chlorhexidine is used in the following areas: health services.
Release to the environment of Chlorhexidine can occur from industrial use: as an intermediate step in further manufacturing of another substance (use of intermediates).
Manufacture of Chlorhexidine:
ECHA has no public registered data on the routes by which Chlorhexidine is most likely to be released to the environment.
Synonyms:
55-56-1
Rotersept
Fimeil
Hexadol
Soretol
Chlorhexidin
Chlorhexidinum
Nolvasan
Hibistat
1,6-Bis(p-chlorophenyldiguanido)hexane
1,6-Di(4'-chlorophenyldiguanido)hexane
UNII-R4KO0DY52L
1,6-Bis(5-(p-chlorophenyl)biguandino)hexane
Chlorohexidine
Exidine
Tubulicid
Sterilon
CHEMBL790
R4KO0DY52L
MLS001332388
CHEBI:3614
Cloresidina
Clorhexidina
56-95-1
Biguanide, 1,1'-hexamethylenebis(5-(p-chlorophenyl)-
CAS-55-56-1
NCGC00016246-03
SMR000857146
Sterido
Savlon babycare
DSSTox_CID_13314
DSSTox_RID_79062
DSSTox_GSID_33314
Chlorhexidine [INN:BAN]
Chlorhexidine dihydrochloride
Merfen-incolore
MLS001304094
CCRIS 9230
SR-01000799135
Nolvasan
1,1'-Hexamethylenebis(5-[p-chlorophenyl]biguanide)
SMR000718621
EINECS 200-238-7
Lisium (*Dihydrochloride*)
BRN 2826432
1,6-Di(N-p-chlorophenyldiguanido)hexane
Chlorhexadine
Dentisept
1,6-Bis(N5-[p-chlorophenyl]-N1-biguanido)hexane
Prestwick_53
3697-42-5
Prestwick0_000143
Prestwick1_000143
Prestwick2_000143
Prestwick3_000143
Spectrum2_000135
Spectrum3_000339
Spectrum4_000277
Spectrum5_001322
Hexamethylenebis(5-(4-chlorophenyl)biguanide)
EC 200-238-7
BSPBio_000246
BSPBio_001977
KBioGR_000774
KBioSS_000717
4-12-00-01201
MLS001332387
MLS002154209
DivK1c_000761
SPBio_000210
SPBio_002185
BPBio1_000272
DTXSID2033314
BDBM51937
BDBM64773
cid_9552079
KBio1_000761
KBio2_000717
KBio2_003285
KBio2_005853
KBio3_001197
NINDS_000761
REGID_for_CID_9552079
BDBM152706
HMS1568M08
HMS2095M08
HMS2233B16
HMS3712M08
HY-B1248
Tox21_110325
Tox21_201404
Tox21_303445
BDBM50170723
s5397
STK089248
AKOS005394319
Tox21_110325_1
CCG-220143
CS-4958
DB00878
MCULE-4644073142
QTL1_000020
NCGC00016246-01
NCGC00016246-02
NCGC00016246-04
NCGC00016246-05
NCGC00016246-06
NCGC00016246-07
NCGC00016246-09
NCGC00016246-13
NCGC00016246-21
NCGC00091025-01
NCGC00091025-02
NCGC00091025-04
NCGC00247766-01
NCGC00257242-01
NCGC00258955-01
AS-12648
SBI-0051301.P003
AB00053427
C06902
D07668
AB00053427-24
AB00053427-28
AB00053427_29
009C673
A830704
Q-200828
SR-01000799135-5
BRD-K52256627-300-03-3
BRD-K52256627-300-05-8
SR-01000799135-10
SR-01000799135-11
Regulatory process names:
Chlorhexidine
Chlorhexidine
chlorhexidine
N,N''-bis(4-Chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediamidine
CAS names:
2,4,11,13-Tetraazatetradecanediimidamide, N1,N14-bis(4-chlorophenyl)-3,12-diimino-
IUPAC names:
(1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine
1,1'-Hexamethylenebis[5-(p-chlorophenyl)biguanide]
2,2'-hexane-1,6-diylbis(1-{amino[(4-chlorophenyl)amino]methylidene}guanidine)
CHLORHEXIDINE
Chlorhexidine
chlorhexidine
Chlorhexidine-base
N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]
N,N'"-BIS(4-CHLOROPHENYL)-3,12-DIIMINO-2,4,11,13-TETRAAZOTETRADECANEDIIMIDAMIDE
N-(4-chlorophenyl)-1-{N-[6-(N-{[N'-(4-chlorophenyl)carbamimidamido]methanimidoyl}amino)hexyl]carbamimidamido}methanimidamide
Trade names:
CHD-Base
Other identifiers:
111883-36-4
111883-36-4
1520991-69-8
1520991-69-8
328933-19-3
328933-19-3
55-56-1