Chlorhexidine - Clinical Tree

General information

Chlorhexidine (1,1′-hexamethylene- bis [5-( p -chlorophenyl)biguanide]) is a widely used antibacterial agent with activity against Gram-positive bacteria, Gram-negative bacteria (less against Pseudomonas species), and yeasts. It was introduced as an antiseptic in the early 1950s. It has been primarily used for topical antisepsis, for example in preoperative skin disinfection, and for disinfection of materials, mainly in combination with cetrimide. Long-term experience has shown a low incidence of sensitization and a low irritant potential [ ].

Unwanted effects have resulted from undue reliance on the disinfecting properties of chlorhexidine. Hospital-acquired infections have been caused by infected chlorhexidine used for bladder irrigation and for storage or disinfection of catheter spigots and needles [ , ]. A microbiological analysis of chlorhexidine-cream tubes, repeatedly used by patients with indwelling urethral catheters, showed high contamination with potential pathogens in 32% of cream samples and in 35% of swabs taken from the outside of the tubes beneath the screw cap [ ].

Uses

Dentistry

Chlorhexidine has been used as an adjuvant for plaque control and in the treatment of gingival inflammation. It is generally considered to be effective in the control of plaque and can be helpful in the treatment of gingivitis. It can be applied in the form of a solution, used as a mouth rinse or with a toothbrush, in dentifrice or as a gel. The concentrations used are 0.05–2%.

It is very difficult to summarize the effect of chlorhexidine on oral hygiene, since studies differ markedly as regards the population studied, the occurrence of gingival lesions, the use of other oral hygiene regimens, previous scaling, and polishing of the teeth. The most frequently reported adverse effects of oral use are discoloration of the teeth, tongue, and buccal mucosa, taste disorders, and desquamation of the oral mucosa. A mild increase in gingival bleeding was reported after the use of chlorhexidine mouthwash compared with mechanical cleaning methods.

Neonatal skin care

The withdrawal of hexachlorophene-containing products for routine neonatal skin care stimulated investigations into the possible use of chlorhexidine in this field. Its activity range includes effectiveness of high dilutions against Gram-positive and Gram-negative bacteria, yeasts, and molds. In studies of nursery populations, chlorhexidine appears to be as effective as hexachlorophene in preventing staphylococcal colonization and infection. However, there is no evidence that chlorhexidine promotes Gram-negative colonization in neonates bathed in water-containing chlorhexidine [ ].

Data presented in three studies have provided substantial evidence that there is very low percutaneous absorption in full-term infants and also in excessively exposed newborn rhesus monkeys. However, traces of chlorhexidine were found in adipose tissue (two of five monkeys), kidneys (five of five), and liver (one of five), suggesting some absorption percutaneously or by oral ingestion, following the rigorous bathing procedure in the above study. The grooming habits of the monkeys could have played a role [ ].

Neonatal cord care

About 0.2 ml of undiluted 4% chlorhexidine solution with a detergent was included in the daily routine of rubbing the dry cord stump and the surrounding skin, which were then rinsed and dried. No chlorhexidine was detectable in the blood samples of the neonates, taken on the fifth day [ ].

Spermicides

The use of chlorhexidine in spermicides has been promoted as a strategy for protecting against sexually transmitted diseases, including HIV infection. However, both the claim of protection and the cytotoxicity of chlorhexidine, with a risk of damage to the epithelia of the vagina, cervix, and glans penis due to chronic exposure, have to be further validated [ ].

Venesection

To minimize the bacterial contamination rate in blood collected from donors a study was designed to evaluate the suitability of a single-use chlorhexidine-alcohol antiseptic for donor arm preparation at all blood collection venues in Australia [ ]. The tolerability of an antiseptic for blood donor disinfection is important to minimize any factor that might cause donors to stay away from future donation. A prospective study of bacterial load on the skin was performed in 616 blood donor arms before and after disinfection. Disinfection was achieved with a swab containing 1% chlorhexidine gluconate with 75% alcohol. Feedback from blood donors and staff was obtained using questionnaires. After disinfection, there was a marked reduction in skin bacterial counts, well under the target of the Australian Red Cross Blood Services. Sixteen donors reported skin irritation at the site of application; most of the reactions were self-limiting itchiness, with or without erythema. The majority of donors either preferred or did not object to the use of the chlorhexidine antiseptic.

Prevention of HIV transmission during labor

An estimated 600 000 children world-wide were infected with HIV type 1 in 2001. Most of these infections occurred through mother-to-child transmission of HIV during pregnancy, around the time of labor and delivery. In developing countries, where the resources to prevent and manage these infections are limited, peripartum cleansing with chlorhexidine is a potentially simple and low-cost strategy for the prevention of mother-to-child transmission. However, low concentrations of chlorhexidine have not been proved to be effective in reducing mother-to-child transmission. Before assessing the effectiveness of higher chlorhexidine concentrations on mother-to-child transmission the highest tolerated concentration needed to be established. Three concentrations of chlorhexidine (0.25%, 1%, and 2%) have been evaluated as perinatal maternal and infant washes, to identify the maximum tolerated concentration for this intervention [ ]. Women were enrolled during their third trimester at a maternity unit in Soweto, South Africa. Subjective maternal symptoms and infant examinations were used to assess tolerability of the washes. The 0.25% concentration of chlorhexidine was well tolerated by the mothers. Ten of 79 complained of mild vaginal burning or itching from the 1% chlorhexidine washes, and washes were stopped in five. Of the 75 women in the 2% chlorhexidine group, 23 had subjective complaints and the washes were stopped in 12. There were no indications of toxicity from any of the chlorhexidine washes in the infants. The authors concluded that a 1% solution of chlorhexidine is safe and well tolerated and could be considered for a trial in the prevention of mother-to-child transmission.

Five studies of the prophylactic intravaginal use of chlorhexidine vaginal suppositories before delivery and in obstetrics have been reviewed [ ]. No severe adverse reactions were reported.

Drug studies

Observational studies

Chlorhexidine has been used extensively for many decades as a broad-spectrum antiseptic in hospitals and elsewhere. It has 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.

Placebo-controlled studies

In a multicenter, double-blind, randomized, placebo-controlled study, two decontamination regimens were assessed in the prevention of acquired infections in 515 high-risk intubated patients in intensive care [ ]:

topical polymyxin + tobramycin (n = 130);
nasal mupirocin ointment with chlorhexidine body washing (n = 130);
the two regimens combined (n = 129);
matching placebo (topical placebo and/or nasal placebo + liquid soap; n = 126).

There were fewer acquired infections with the combined regimens than with either regimen alone or placebo. There were no differences between either regimen alone and placebo. There were allergic reactions in six patients who received chlorhexidine and six patients who received the liquid soap. There was no intolerance to the nasal ointment. The polymyxin + tobramycin regimen was withdrawn in 37 patients, mostly because the serum tobramycin concentration exceeded 2 mg/l. Body washing was discontinued in nine patients receiving chlorhexidine and in eight patients receiving the liquid soap.

In 60 patients who were randomized to 2% typified propolis (n = 20), 0.12% chlorhexidine (n = 20), or placebo (n = 20) and rinsed unsupervised twice a day for 28 days, propolis mouth rinse was more efficacious than chlorhexidine; 23 adverse reactions were attributed to chlorhexidine, including a burning sensation, altered taste, yellow teeth, altered breath, tongue burning, mucosal irritation, and a bitter taste, compared with seven reactions to propolis, including altered breath, a burning sensation, yellow teeth, altered taste, and a bitter taste, and nine events related to altered taste in those who used placebo [16].

Systematic reviews

A review of the literature on chlorhexidine interventions (vaginal, newborn skin, and umbilical cord cleansing) focused on neonatal outcomes and safety. In summary, tens of thousands of neonates have received these chlorhexidine-based cleansing interventions without reported adverse effects. However, the data on safety are incomplete. Although the chlorhexidine concentrations used and reported thus far appear to be safe, the upper level of chlorhexidine that can be considered safe is not known and further research is required to inform public health safety in developing countries [ ].

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