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Effects of a chlorhexidine varnish on the gingival status of adolescents.

The purpose of this blind study was to determine the effect of a two-stage chlorhexidine varnish, after three months, on the gingival status of 11- to 15-year-old children attending a school in Rio de Janeiro, Brazil. Subjects participating in the study were randomly allocated to control (C) and treatment (T) groups, n = 53 and n = 57, respectively. All subjects were matched at baseline on age, salivary levels of mutans streptococci, and caries scores. After elimination of carious lesions, a prophylaxis was given to both groups. The chlorhexidine varnish was then painted on the entire dentition of Group T subjects only. Prior to caries elimination, and again after three months, the gingival index was used to assess the gingival status of study subjects. An average of 106.6 +/- 8.9 and 107.7 +/- 6.2 gingival sites per subject (four sites per tooth) in Groups C and T, respectively, were examined by the same calibrated examiner on two occasions. For statistical purposes, data were dichotomized [(0,1) (2,3)] for the gingival index. Independent t-tests and paired t-tests were used to analyze the data. The percentage of sites per subject with scores of two or three at the baseline were balanced between study groups (3.7 +/- 7.1 for T; 1.8 +/- 3.2 for C; p = 0.08). After three months, a statistically significant decrease in the average percentage of sites with scores of two or three was demonstrated in the T group (0.7 +/- 2.4, T, p < 0.0001; 1.3 +/- 3.0, C, p < 0.25). The authors concluded that the application of a chlorhexidine varnish significantly improved the gingival health of T subjects for up to three months. A significant improvement in the gingival health could not be demonstrated in the C group.

Adolescent↗

Chlorhexidine rinsing in physically handicapped pupils in Katlehong.

Poor oral hygiene and a high prevalence of marginal gingivitis are characteristic findings in handicapped persons. The present double-blind, cross-over study was to evaluate a twice daily mouth rinse of 10ml 0.2 per cent chlorhexidine on plaque and gingivitis in physically handicapped pupils aged 6 to 21 years. The plaque index (PI) and gingival index (GI) at baselines were relatively lower than in other published studies. For PI the mean score did not exceed 1.0 at any time; for GI the same was true except for tooth 16 which was 1.1. Only mild gingival inflammation was present. The chlorhexidine rinse produced 34 per cent to 54 per cent improvement in PI values and 48 per cent to 52 per cent improvement in GI values. Highly statistically significant effects were seen for treatment and time but there was no significant learning effect. Whether the children lived at home or at the study school had no significant effect. The chlorhexidine rinse may be successfully used in physically handicapped children but the low gingival inflammation in the group suggests that simple oral hygiene improvement might produce the same effect.

Adolescent↗

[Inactivation of chlorhexidine for in vitro testing of disinfectants].

An insufficient neutralization of chlorhexidine (4%), tested in vitro against Enterococcus faecium ATCC 6057, was suspected in the quantitative suspension test although the combination Tween 80, cysteine, histidine and saponine was assessed as sufficient for neutralising chlorhexidine. Bactericidal activity of each neutralising compound and their combinations was excluded. Sufficient neutralization was observed when all dilution steps and the corresponding agar plates were supplemented with the neutralising compounds. Successful neutralization in broth is not equivalent with successful neutralization in tryptic saline. We suggest to supplement at least the agar plates of the first dilution step with neutralising compounds when testing chlorhexidine.

Anti-Infective Agents, Local↗

Histologic study of pulp capping using chlorhexidine in dogs.

This histological study was conducted to compare the pulp reactions to chlorhexidine and calcium hydroxide. Twenty permanent premolar teeth of beagle dogs were mechanically exposed under aseptic conditions. The pulp was then capped with one of the following: chlorhexidine 0.2% on the left side and calcium hydroxide (dycal) on the right side of the same dog. Maxillary second premolars were extracted from each dog three weeks after the pulp capping procedure. Maxillary third premolars and mandibular first premolars were extracted at 6 weeks and 9 weeks respectively. The mandibular second premolars were extracted three months after the pulp capping procedure. The specimens were fixed in 10% formalin and decalcified in 5% formic acid. Serial sections, 7 microns thick, were prepared and stained with hematoxylin and eosin. Teeth treated with chlorhexidine or with calcium hydroxide were well tolerated by the dental pulp at 3 and 6-week intervals. Pulps treated showed satisfactory pulp reaction and the odontoblastic layer appeared to be normal and in its configuration. Inflammatory response was not present at the 6-week time interval. At nine weeks, the inflammatory response was severe in those teeth treated with calcium hydroxide. There were no remarkable histological differences among the treatment groups at 12 and 15 weeks. These specimens showed complete loss of pulpal architecture. Regressive changes were seen and microscopic specimens revealed presence of spaces and intertwining bundles of films in the pulp.

Animals↗

Chlorhexidine, fluoride varnish, and xylitol chewing gum: underutilized preventive therapies?

The successful implementation of a preventive dentistry program depends, to a large extent, on the compliance of the patient. The scheduled program would include: recall appointments, all instructions relative to oral hygiene, use of nightly fluoride rinses, and control of diet. To ensure that high-risk patients who have cariogenic bacteria are adequately treated, chlorhexidine rinses may be required on a periodic basis. The patient's level of risk must determine all treatment decisions. For low-risk patients, the times between recall appointments can be extended when evidence of caries arrest and remineralization can be documented. High-risk patients should be recalled at least every three months, until evidence of lesion arrest and/or remineralization has been documented. For patients with extremely low saliva flow rates, the combined chlorhexidine and fluoride method may be required. If the caries risk is still judged to be high according to bacteria counts and/or evidence of further lesion development or progression, more frequent applications of chlorhexidine may be required. Because fluoride varnish is generally more effective on smooth surfaces than on fissure sites, moderate caries-risk patients should receive fluoride varnish on smooth surfaces, and sealants, when indicated, on fissure sites. As the caries risk of the patient is reduced to a low-risk level, less frequent use of fluoride-containing or fluoride releasing products is indicated, and there can be longer periods between recall examinations. Three applications of fluoride varnish, applied to a single week, appear to provide greater caries protection than two applications per year. Attempts should be made to ensure that the varnish is applied immediately after cleaning the teeth and protected as long as possible after the varnish has been applied (preferably at least 10 hours). Fluoride varnish appears to be as effective as topical fluoride gel and may be safer. Thus, a greater frequently of application is permitted without a significant risk of fluorosis. Prevention is more cost effective as the patient shifts from a high-risk level to a low-risk level. Recall appointments can subsequently be extended and more conservative prevention treatments are warranted. Over an extended treatment period, the cost for the preservative dentistry option should be comparable to and perhaps less than the cost of placing and replacing dental restorations.

Chewing Gum↗

Safety and efficacy of the antiseptic chlorhexidine gluconate.

Chlorhexidine gluconate, an antiseptic for the skin, has recently been investigated in a series of clinical studies on its safety and efficacy. By using standard methods, Hibiclens, Hibitane tinted tincture and 0.5 per cent aqueous chlorhexidine gluconate were shown to have an extremely low potential for the production of irritation, allergic contact sensitization, photoallergic contact sensitization and phototoxicity. In the glove fluid test for efficacy against resident flora of the hand, Hibiclens produced log10 reductions over the control of 1.9398, 2.5371 and 2.6885 for test days 1, 2 and 5, respectively. Corresponding reductions for Hibitane tinted tincture were 3.6903, 4.0984 and 4.1253 and for the aqueous formulation, 1.5003, 1.5721 and 1.8692. In a transient flora skin contamination study, Serratia marcescens was applied at an average level of 6.8363 log10 organisms per milliliter to persons' hands, after which a 15 second Hibiclens hand wash was performed. Following five of these contaminations and hand washes, there was an over-all log10 reduction in recoverable Serratia of 3.8500. Counts were further determined after ten, 15, 20 and 25 contaminations and hand washes, resulting in corresponding reductions of 4.2649, 4.6661, 4.8501 and 5.1725, respectively. Chlorhexidine gluconate offers an alternative to available antiseptics for the skin. It has been shown to be a fast acting, broad spectrum antimicrobial agent, with an extremely low potential for eliciting dermal reactions.

Adult↗

Fissure penetration and antibacterial effect in vitro of a glass ionomer cement containing chlorhexidine gluconate.

Chlorhexidine has been incorporated in different varnishes to provide a slow release system on the tooth surface in order to reduce mutans streptococci. To provide an alternative vehicle for chlorhexidine with better adhesion properties compared to resin-based varnishes, glass ionomer cement (GI) has been suggested. However, one disadvantage for glass ionomers is a longer setting time compared to the resin-based varnishes. The aim with this study was to compare the fissure penetration and antibacterial characteristics of a glass-ionomer cement (GI) with a GI containing chlorhexidine gluconate (GI-CHX), and GI-CHX with added tataric acid (GI-CHX-TA) to reduce its setting time. Antibacterial properties against mutans streptococci were assessed by agar diffusion. GI, GI-CHX and GI-CHX-TA were applied with a microbrush on the occlusal surfaces of 4, 4 and 6 extracted molars respectively. After setting of cements, sections were ground with 1 mm intervals and photographed. The fissure penetration and adaptation of the cements were scored excellent, acceptable or unacceptable under blind conditions according to a standard. Seventy percent scored excellent with GI-CHX-TA (n = 54) compared with 40% with GI-CHX (n = 48) and 38% with GI (n = 40), (p < 0.05). GI-CHX and GI-CHX-TA had significant better antibacterial properties compared to GI or GI with added tataric acid only.

Analysis of Variance↗

Severe anaphylaxis to a new disinfectant: polyhexanide, a chlorhexidine polymer.

We describe the cases of an 18-year-old female and a 15-year-old male who developed severe anaphylaxis following contact of surgical wounds with the disinfectant Lavasept, containing polyhexanide, a polymerised form of chlorhexidine, during orthopaedic interventions. According to the manufacturer, this product is the only polyhexanide containing medical disinfectant, has recently been commercialised and is only available in Switzerland. One of the patients denied previous contact with this compound but both patients were previously exposed to chlorhexidine. Immediate-type hypersensitivity to polyhexanide was suggested by positive skin prick tests in the two patients and by negative skin tests in control individuals. Skin tests with chlorhexidine in the patients remained negative. We conclude that contact with the new disinfectant Lavasept can trigger anaphylactic reactions, even in the absence of previous history of exposure to this compound. It remains to be established whether this new disinfectant is a frequent anaphylactogen.

Administration, Topical↗

Chlorhexidine resistance in Proteus mirabilis.

A total of 104 clinical isolates of Pr. mirabilis from three hospitals were screened for their sensitivity to chlorhexidine. The minimum inhibitory concentrations of the antiseptic for these strains ranged from 10 to 800 mug/ml. Two strains sensitive to 20 mug of chlorhexidine/ml were adapted to resistance by growth in subinhibitory concentrations of the antiseptic, their MIC values increasing to 200 and 800 mug/ml. These derived strains exhibited slightly reduced sensitivity to cetrimide and benzalkonium chloride. The chlorhexidine-resistant clinical isolates also exhibited this partially decreased sensitivity to the quaternary ammonium compounds. Both the chlorhexidine-sensitive and -resistant strains were uniformly sensitive to chloroxylenol (Dettol), glutaraldehyde, and 2-phenoxyethanol.

Benzalkonium Compounds↗

Delivery challenges for fluoride, chlorhexidine and xylitol.

The progression or reversal of dental caries is determined by the balance between pathological and protective factors. It is well established that a) fluoride inhibits demineralization and enhances remineralization, b) chlorhexidine reduces the cariogenic bacterial challenge, and c) xylitol is non-cariogenic and has antibacterial properties. The challenge that we face is how best to deliver these anti-caries entities at true therapeutic levels, over time, to favorably tip the caries balance. High caries risk people, including children with Early Childhood Caries (ECC), are a special challenge, since high cariogenic bacterial activity can override fluoride therapy. Current fluoride and chlorhexidine varnishes deliver all their activity within about 24 hours. Early studies with experimental slow release fluoride devices retained elevated levels of fluoride for months in a therapeutic range but have not been pursued. Preventive dentistry has largely ignored the benefits of reducing the bacterial challenge, partially due to primitive and inadequate delivery systems. For example, Chlorhexidine applied as a rinse partially reduces some bacteria but not others that are hiding within the biofilm. Better antibacterials and better delivery systems are needed. Xylitol delivered by gum or lozenge appears to be effective clinically in reducing cariogenic bacteria and caries levels, but novel systems that deliver therapeutic amounts when needed would be a major advance, especially for young children. Reducing the cariogenic bacterial challenge and enhancing the effect of fluoride by the use of new sustained-delivery systems would have a major effect on dealing with caries as a disease.

Journal Article↗

Disinfection of eyelid specula with chlorhexidine gluconate (Hibiclens) after examinations for retinopathy of prematurity.

BACKGROUND: The preferred method of cleaning eyelid specula between examinations for retinopathy of prematurity is unknown. A previous study showed that disinfection with 70% isopropyl alcohol swabs fails to eliminate viruses and bacteria from the specula. OBJECTIVE: To determine if alternative sterilization procedures would allow multiple use of a single speculum without risking nosocomial infection. METHODS: In phase 1, 40 autoclave-sterilized eyelid specula were randomized into either "cleaned" or "patient control" groups after being used for routine retinopathy of prematurity examinations performed in the outpatient setting. Specula in the cleaned group were cleaned with chlorhexidine gluconate (Hibiclens). Specula in the patient control group were not cleaned after use. All study specula were placed into enriched culture media from which bacterial and fungal cultures were obtained. In phase 2, 20 autoclave-sterilized eyelid specula were inoculated with a clinically relevant dilution of adenovirus serovar 5 or herpes simplex type 2. Specula were randomized into either a cleaned or a control group, and cell cultures and immunofluorescence assays were used to document and confirm, respectively, viral growth. RESULTS: In phase 1, all 20 cultures from the patient control group grew bacteria compared with 0 (0%) of 20 cultures from the cleaned group and 0 (0%) of 5 from the cleaned control group. No fungi were isolated from any group. In phase 2, all 10 cultures from specula inoculated with adenovirus serovar 5 grew virus. None of the cultures from the 5 cleaned specula inoculated with herpes simplex type 2 grew virus. In contrast, all 5 cultures in the control group were positive for growth of herpes simplex type 2. CONCLUSIONS: Autoclave sterilization is the ideal method of sterilization of eyelid specula between neonate examinations. When an alternative disinfection technique is required, washing the speculum with chlorhexidine gluconate and tap water is preferred over wiping with a 70% isopropyl alcohol swab. Arch Ophthalmol. 2000;118:786-789

Adenoviruses, Human↗

Examination of the physical state of chlorhexidine within viscoelastic, bioadhesive semisolids using raman spectroscopy.

This study examined the effects of polymeric components on the physical state of chlorhexidine within bioadhesive, semisolid formulations using Raman spectroscopy. Semisolid formulations were prepared in which chlorhexidine base (CHX, 5%w/w, particle size <63 microm) was dispersed in aqueous (phosphate-buffered saline, pH 6.8) polymer matrices consisting of one or more polymeric components, namely HEC (3%w/w), PVP (3%), and PC (PC, 3%). Raman spectra were recorded using 785-nm excitation and were typically accumulated for 360 s. The Raman spectra were dominated by the presence of CHX. The spectra of CHX in HEC and in HEC/PVP gels were indistinguishable from that for solid CHX as a result of the insolubility of CHX in these formulations. However, in systems containing PC and CHX, there was a shift in the strongest band from 1564 cm(-1) to 1608 cm(-1), which may be accredited to protonation of the basic CHX by the numerous carboxylic acidic groups on PC. Identical shifts in the band positions were observed when this protonation was modeled using ethanoic acid, supporting the view that there was a simple acid base reaction between PC and CHX. However, there were notable differences in the relative intensities of the peaks from these samples, with the spectrum of CHX in the PC matrix displaying properties intermediate between those of CHX dissolved in ethanoic acid and solid CHX diacetate. This may be accredited to the limited solubility of the CHX-PC ion pair. In matrices containing HEC and PC, no peak was observed at 1564 cm(-1), whereas the intensity of the peak at 1608 cm(-1) was increased. Therefore, in these formulations CHX was completely converted to the di-cation as a result of the synergistic effects of PC (which protonated CHX) and HEC (which solubilized the di-cation). In the absence of either HEC or PC, complete protonation was not achieved. It is suggested that this enhancement of solubility of H(2)CHX(2+) may be due to hydrogen bonding, given the hydroxylated nature of HEC. In conclusion, this study has shown the applicability of Raman spectroscopy for both the analysis of opaque, semisolid formulations and, additionally, for the examination of the state of therapeutic agents within such matrices. In particular, using Raman spectroscopy, it was uniquely possible to identify the roles of various polymeric components on both the ionization and solubilization of CHX within aqueous semisolid systems.

Chemistry, Pharmaceutical↗

Gravimetric determination of chlorhexidine using tetraphenylborate ion.

A precise and accurate gravimetric procedure was developed for the determination of chlorhexidine diacetate, digluconate, or dihydrochloride. Sodium tetraphenylborate solution was the precipitant in an acidic medium (pH 1). Tablets containing both chlorhexidine diacetate and benzocaine also were assayed.

Biguanides↗

Rapid colorimetric analysis of chlorhexidine in pharmaceutical preparations.

A colorimetric determination of chlorhexidine is described. The method is based on the formation of a yellow complex between the drug and bromcresol green. The absorption peak of this complex, extracted by chloroform, is at 410 nm, and linear response is obtained from 2.5 to 30 micrograms of chlorhexidine/ml. The accuracy and reproducibility of this rapid method make it useful for chlorhexidine determination in the manufacturing control of pharmaceutical mixtures.

Chlorhexidine↗

Mucosal injuries following intratympanic applications of chlorhexidine gluconate in the cat.

We investigated the morphological changes of the middle ear mucosa of the cat exposed to two different concentrations of the disinfectant, chlorhexidine gluconate. In the high concentration (2%) group, notable destructive changes were found on the mucosal surfaces in the tympanic cavity and were especially most severe in that area lined with few ciliated cells under normal conditions. Cilia were twisted and decreased in length in this site. At the tympanic orifice of the eustachian tube, cilia were distributed densely and showed little destructive changes on the surface. In the clinical concentration (0.05%) group, mucosal injuries generally seemed more slight when compared with those in the high concentration group. However, a decrease in the number of cilia or actual loss of cilia was one of the features in this group. Infrequent defects of the superstructures of the epithelial cells were noted on the mucosal surface, but these injuries appeared to spare the basal lamina. In both groups, there were no calcified pathologies seen and no complete obliterations by thickened mucosa or granulations. Deterioration of the ciliary system by chlorhexidine gluconate seems to produce subsequent cell destruction of the middle ear mucosa.

Animals↗

Chlorhexidine-induced degeneration of adrenergic nerves.

Possible toxic effects of chlorhexidine (CHX) on the sympathetic adrenergic ground plexus were studied in whole mounts of albino rat irides using Falck-Hillarp fluorescence histochemistry. CHX dissolved in an isotone , buffered sodium-acetate solution or in 70% alcohol was injected into the anterior chamber of eye. CHX caused a marked and dose-dependent degeneration of adrenergic nerves. Two days after the lowest dose, 0,25 micrograms (5 microliters of a 0.05% CHX solution), approximately 30% of the nerves had disappeared. Almost complete degeneration was observed after the same time with higher doses (2.5 micrograms, 5.0 micrograms, and 7.5 micrograms corresponding to 0.5, 1.0, and 1.5% CHX respectively). Two weeks after the lowest dose, the nerves had regenerated almost completely. With the highest dose used, only some 40% of the normal adrenergic nerve plexus had reformed after 51 days. Alcohol as a solvent did not have an additive effect on the neurotoxic action caused by CHX. The results demonstrate yet another aspect of chlorhexidine neurotoxicity, degeneration of peripheral adrenergic nerve terminals. This suggests that neurotoxic actions on thin unmyelinated fiber systems should be looked for also in the central nervous system (CNS).

Animals↗

Action of chlorhexidine on budding Candida albicans: scanning and transmission electron microscopic study.

Chlorhexidine is widely used as a bacterial drug whose method of action has been well described in bacteria. Its fungicidal properties have been proved. We show here the effects of a sublethal dose of a preparation of digluconate of chlorhexidine on budding Candida albicans. A fungistatic action is revealed by a decrease in the percentage of budding cells, and two main types of alterations can be observed with transmission electron microscopy (T.E.M.): a loss of cytoplasmic components and a coagulation of nucleoproteins. With scanning electron microscopy (S.E.M.), the cell walls show morphological modifications.

Candida albicans↗

Chlorhexidine: antibacterial action and bacterial resistance.

Chlorhexidine is a clinically important antiseptic, disinfectant and preservative. It is a potent membrane-active agent against bacteria and inhibits outgrowth, but not germination, of bacterial spores, although it is not sporicidal. It shows high activity against wild-type and outer membrane mutants of Escherichia coli but some gram-negative bacteria are resistant to chlorhexidine by mechanisms not yet fully understood, although they appear to involve the outer, rather than the inner, membrane.

Bacteria↗