Retention and plaque-inhibiting effect in man of chlorhexidine after multiple mouth rinses and retention and release of chlorhexidine after toothbrushing with a chlorhexidine gel.
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Adult↗
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The specificity of murine polyclonal and monoclonal antibodies to the haptenic drug chlorhexidine induced by chlorine-generated chlorhexidine-protein conjugates.
Polyclonal and monoclonal antibodies to the antibacterial agent chlorhexidine (1,1'-hexamethylene bis [5-(p-chlorophenyl)]biguanide, mol. wt = 505) were raised using a chlorine-generated N-chloro chlorhexidine-keyhole limpet haemocyanin (NCC-KLH) conjugate as the immunogen. Antibodies were detected by ELISA, using a semi-chlorhexidine derivative conjugated to human serum albumin (SC-HSA) as the antigen. Free chlorhexidine could completely inhibit both polyclonal and monoclonal antibody binding to SC-HSA. Direct binding and inhibition ELISA studies revealed that the N-chlorination of chlorhexidine does not significantly alter its specificity as an immunogen or antigen and that chlorhexidine has two identical epitopes. Each epitope consists of the p-chlorophenyl biguanide structure of which the terminal p-chlorophenyl group appears to be immunodominant. Chlorhexidine is, therefore, a symmetrical divalent hapten and this implies that it may be capable of eliciting immediate hypersensitivity reactions by divalent interaction with antibodies induced by chlorine-generated N-chloro-chlorhexidine-protein immunogens. The clinical significance of these findings is discussed.
Animals↗
Chlorhexidine for prevention of neonatal colonization with group B streptococci. V. Chlorhexidine concentrations in blood following vaginal washing during delivery.
Chlorhexidine 2 g/l was applied to the vagina of 96 women during delivery, whereas 28 served as controls. Both groups were given a shower using a chlorhexidine soap, and outer washing of the outer anogenital tract was also performed in all patients using chlorhexidine 2 g/l. Using a gas chromatographic method with a detection limit of 10 ng chlorhexidine per ml blood, 10-83 ng/ml was demonstrated in 34 (35%) of the study group patients, whereas the remaining study group patients and controls showed no detectable chlorhexidine. Performing the washing a second time after 6 hours in 14 patients and a third time in 3 patients after a further 6 hours did not result in increased serum levels. It was concluded that small amounts of chlorhexidine are absorbed through the vaginal mucosa and that chlorhexidine is not accumulated in the blood on repeated usage with 6 hour intervals during delivery.
Administration, Intravaginal↗
In vitro assessment of the effectiveness of chlorhexidine gel and calcium hydroxide paste with chlorhexidine against Enterococcus faecalis and Candida albicans.
OBJECTIVE: The purpose of this study was to compare the effectiveness of various medicaments, including Ca(OH)2/2% chlorhexidine, 2% chlorhexidine gel, and Ca(OH)2 alone, against Enterococcus faecalis and Candid albicans in vitro. STUDY DESIGN: Eighty extracted single-rooted human maxillary teeth were used. After removing the crown, each root was instrumented up to size 50 by using a conventional technique. The root canal was irrigated with ethylenediamine tetra-acetic acid (EDTA) solution to remove smear layer. Then, roots were infected with E faecalis and C albicans. Subsequently, the roots were divided into 4 treatment groups: group 1 was treated with calcium powder hydroxide in distilled water, group 2 was treated with calcium hydroxide powder in 2% chlorhexidine, group 3 was treated with 2% chlorhexidine gel, and group 4 was treated with 0.9% sterile saline serving as negative control. Microbial samples were taken after 7, 15, and 30 days. After incubation, dentine chips were obtained form each root canal and examined microbiologically. The microbiological samples were plated to count colony-forming units in per milligram of dentin. RESULTS: The results showed that the 2% chlorhexidine gel was significantly more effective than calcium hydroxide with 2% chlorhexidine, calcium hydroxide, and control saline solution (P < .05). CONCLUSION: Under the conditions of this study, 2% chlorhexidine gel is effective in the elimination of E faecalis and C albicans from the root canal system. However, to support this in vitro observation, further in vivo studies are needed.
Anti-Infective Agents, Local↗
Dissolution of pulp tissue by aqueous solution of chlorhexidine digluconate and chlorhexidine digluconate gel.
AIM: To evaluate the activity of various root canal irrigants on bovine pulp tissue. METHODOLOGY: The irrigants tested were: 0.5, 1.0 and 2.5% sodium hypochlorite; 2% aqueous solution of chlorhexidine digluconate; 2% chlorhexidine digluconate gel (Natrosol); and distilled water as control. Bovine pulp fragments were weighed and placed in contact with 20 mL of each tested substance in a centrifuge at 150 r.p.m. until total dissolution. Dissolution speed was calculated by dividing pulp weight by dissolution time. Statistical analysis was performed using the Kruskal-Wallis test. RESULTS: Distilled water and both solutions of chlorhexidine did not dissolve the pulp tissue within 6 h. Mean dissolution speeds for 0.5, 1.0 and 2.5% sodium hypochlorite solutions were 0.31, 0.43 and 0.55 mg min(-1), respectively. The solvent ability of chlorhexidine solutions was similar to that of distilled water. The results for sodium hypochlorite solutions, chlorhexidine solutions and distilled water were statistically different (P>0.01). CONCLUSIONS: Both chlorhexidine preparations and distilled water were not able to dissolve pulp tissue. All sodium hypochlorite solutions were efficient in dissolving pulp tissue; the dissolution speed varied with the concentration of the solution.
Animals↗
Effect of chlorhexidine gel treatment supplemented with chlorhexidine varnish and resin on mutans streptococci and Actinomyces on root surfaces.
The supplementary effect of chlorhexidine varnish and resin on the reappearance of mutans streptococci and Actinomyces spp. on root surfaces after chlorhexidine gel treatment was studied. In 8 subjects with many restored tooth and exposed root surfaces, highly colonized with mutans streptococci, chlorhexidine varnish and resin were applied to the teeth on one side of the mouth and resin alone to the other side. This treatment significantly prolonged the time period of reduced salivary levels of mutans streptococci when added to a preceding period of chlorhexidine gel treatment. In 3 of the 8 subjects, mutans streptococci were undetected for more than 4 weeks after treatment. There was a significant difference between the chlorhexidine varnish/resin side and the resin side for 5 weeks with regard to the mean numbers of mutans streptococci in root surface plaque, whereas for the Actinomyces spp. no significant differences were found. In 2 subjects harboring both Streptococcus mutans and S. sobrinus, the population of S. sobrinus reappeared more readily in saliva and plaque than S. mutans. The chlorhexidine treatment was less effective in suppressing the population of Actinomyces viscosus/naeslundii than the mutans streptococci.
Actinomyces↗
[Studies on resistant mechanisms in the resistant bacteria to chlorhexidine. II. Chemical components of the cell membrane and the electron microscopical observation of cell surface structure of chlorhexidine-resistant bacteria].
The mechanisms of resistance of Serratia marcescens and Pseudomonas cepacia to chlorhexidine were studied. Leakage of the cellular component such as protein was observed in a chlorhexidine sensitive strain (S1) of S. marcescens when S1 was treated with chlorhexidine at 40 micrograms/ml concentration, while this phenomenon was not observed in a resistant strain (R1). The following observations were made concerning about cell surface structure in the chlorhexidine sensitive and resistant strains of S. marcescens by chemical analyses of membrane components and electron microscopical studies of the thin sections of the cells. (1) When the S1 strains was treated with chlorhexidine, the outer membrane of the cells formed a wrinkled surface with irregular blebs, and some of which broke out to form various sizes of granules. The R1 strain did not undergo such morphological changes under the same conditions used in the sensitive strain. (2) A prominent protein with apparent molecular weight of 45 K was found exclusively in the R1 strain of S. marcescens as major outer membrane protein, while it was not found in S1 strain. (3) There were no differences in the composition of phospholipids and the amount of 3-hydroxytetradecanoic acid between S1 and R1 strains of S. marcescens. In Pseudomonas cepacia PCJ1 which is resistant to chlorhexidine, 50 K protein was also observed as a major protein of outer membrane of the cells. In contrast to the strain, a mutant of the strain, #102 which was obtained from PCJ1 strain by the treatment with methanesulfonic acid ethylester, did not possess the 50 K protein in its outer membrane. These data suggested that outer membrane components of bacteria were related importantly in resistant mechanism.
Bacterial Proteins↗
Analysis of chlorhexidine sorption in soft contact lenses by catalytic oxidation of [14C]chlorhexidine and by liquid chromatography.
Two methods are described for the analysis of chlorhexidine sorption in soft contact lenses. The first is an isocratic ion-pairing high-performance liquid chromatographic (HPLC) method with UV detection at 220 nm that allows the determination of chlorhexidine, p-chloroaniline, and other chlorhexidine degradation products in ophthalmic solutions. This procedure had a detection limit of 0.1 ng. The second involves the catalytic oxidation of the lens matrix containing [14C]chlorhexidine to [14C]carbon dioxide and water. The label is then trapped as carbon dioxide in a cocktail and is analyzed by liquid scintillation counting. These methods are sensitive, accurate, and reproducible, and can be used independently or in conjunction for the determination of chlorhexidine sorption in soft contact lenses.
Adsorption↗
Reduction of salivary S. aureus and mutans group streptococci by a preprocedural chlorhexidine rinse and maximal inhibitory dilutions of chlorhexidine and cetylpyridinium.
OBJECTIVES: Staphylococcus aureus and mutans group streptococci can cause, among many other diseases, infective endocarditis and postoperative infections. The reduction of the number of these microorganisms in the oral cavity prior to surgical procedures has been related to a decreased incidence of such occurrences. The aim of this study was to evaluate the effect of a single preprocedural rinse with 0.12% chlorhexidine solution (Periogard) on the salivary counts of S aureus and mutans group streptococci and determine maximal inhibitory dilutions (MID) of this and 0.05% cetylpyridinium chloride solution (Cepacol). METHOD AND MATERIALS: Saliva was collected from 60 patients before and after 30-second mouthrinses with chlorhexidine and cultured in appropriate media. The number of microorganisms was calculated based on the colony-forming units (CFUs). For the in vitro MID determination, 25 strains of S aureus were seeded in the media containing one of the sequential dilutions of both antiseptics. RESULTS: S aureus, Streptococcus mutans, and Streptococcus sobrinus were initially isolated from 45%, 63%, and 28% of the patients, respectively. After rinsing with chlorhexidine, the reductions in the CFUs were above 99% for all the studied microorganisms. In the MID determination, all isolates were inhibited with 1/20 and 1/80 dilutions of cetylpyridinium and chlorhexidine, respectively. Dose-response curves were obtained for both antiseptics. CONCLUSION: Single preprocedural chlorhexidine mouthrinse is effective in reducing salivary microorganisms to levels currently considered safe to perform invasive procedures, and it is still effective in a 1:80 dilution.
Adolescent↗
Prevention of excess neonatal morbidity associated with group B streptococci by vaginal chlorhexidine disinfection during labour. The Swedish Chlorhexidine Study Group.
Streptococcus agalactiae transmitted to infants from the vagina during birth is an important cause of invasive neonatal infection. We have done a prospective, randomised, double-blind, placebo-controlled, multi-centre study of chlorhexidine prophylaxis to prevent neonatal disease due to vaginal transmission of S agalactiae. On arrival in the delivery room, swabs were taken for culture from the vaginas of 4483 women who were expecting a full-term single birth. Vaginal flushing was then done with either 60 ml chlorhexidine diacetate (2 g/l) (2238 women) or saline placebo (2245) and this procedure was repeated every 6 h until delivery. The rate of admission of babies to special-care neonatal units within 48 h of delivery was the primary end point. For babies born to placebo-treated women, maternal carriage of S agalactiae was associated with a significant increase in the rate of admission compared with non-colonised mothers (5.4 vs 2.4%; RR 2.31, 95% CI 1.39-3.86; p = 0.002). Chlorhexidine reduced the admission rate for infants born of carrier mothers to 2.8% (RR 1.95, 95% CI 0.94-4.03), and for infants born to all mothers to 2.0% (RR 1.48, 95% CI 1.01-2.16; p = 0.04). Maternal S agalactiae colonisation is associated with excess early neonatal morbidity, apparently related to aspiration of the organism, that can be reduced with chlorhexidine disinfection of the vagina during labour.
Administration, Intravaginal↗
Measurement of ultrasonic-induced chlorhexidine liberation: correlation of the activity of chlorhexidine-silver-sulfadiazine-impregnated catheters to agar roll technique and broth culture.
The diagnosis of intravascular catheter-related infections continues to be a challenge to both the clinician and the microbiologist. To assess the antiseptic effects of silver-sulfadiazine-chlorhexidine-impregnated central venous catheters (SSC) on catheter culture systems, segments of fresh antiseptic- and non antiseptic-impregnated catheters as well as extracted catheters following five days of immersion in PBS were sonicated. The chlorhexidine liberated from the catheter material by ultrasonication was measured by HPLC. Fresh antiseptic-impregnated catheter segments rolled on seeded agar plates produced inhibition zones unlike catheters which had been extracted for >five days in phosphate buffered saline (PBS). Scanning electron microscopy (SEM) revealed that chlorhexidine-silversulfadiazine crystals were located in the superficial catheter matrix. Direct contact of superficially located drug particles with seeded agar plates probably caused the inhibition of bacterial growth. The study suggests that antiseptic compounds readily elute from fresh catheters during solid medium-based culturing processes and ultrasonication. The addition of inhibitors of silversulfadiazine-chlorhexidine to media may be prudent especially when culturing antimicrobial loaded catheters removed after short inwelling times.
Anti-Infective Agents, Local↗
Antiseptic-induced changes in the cell surface of a chlorhexidine-sensitive and a chlorhexidine-resistant strain of Providencia stuartii.
The effects of chlorhexidine diacetate and benzalkonium chloride on the cell surface of a chlorhexidine-sensitive (Pv 2) and a chlorhexidine-resistant (Pv 67) strain of Providencia stuartii are described. Low concentrations of chlorhexidine diacetate (10 mg/l and upwards) increased the hydrophobicity of Pv 2, whilst having little effect on Pv 67. Both strains were resistant to benzalkonium chloride but a concentration as low as 2 mg/l induced a significant increase in hydrophobicity in Pv 2, with 25-50 mg/l needed to induce a similar type of increase in Pv 67. The possible nature of the resistance is discussed.
Anti-Infective Agents, Local↗
Interaction of chlorhexidine digluconate with and adsorption of chlorhexidine on hydroxyapatite.
It is well known that chlorhexidine digluconate provides an effective microbicidal activity during oral rinsing, and therefore, it was considered worthwhile to investigate its interaction with hydroxyapatite on a fundamental level. The kinetics of uptake (or reaction) of the compound from aqueous solutions by synthetic hydroxyapatite was studied at 23 degrees C for four time periods by monitoring its concentration. There was no uptake at low concentrations for any time period. The uptake curves for higher concentrations shifted towards the lower concentrations as the period increased and became more and more vertically oriented to the concentration axis. The concentrations of calcium ions increased, phosphate ions decreased and hydrogen ions decreased a little for a given period as the concentration of the compound was increased. All of these experimental facts can be qualitatively explained on the basis of the solubility considerations of hydroxyapatite and of chlorhexidine phosphate, the reaction product that slowly precipitates out of the solution. The needle-shaped birefringent crystals of the phosphate salt are clearly visible in the apatite matrix under a microscope, and its refractive index and differential Fourier transform infrared spectra match almost exactly with those of a well-characterized, synthesized phosphate salt. To explore the nature of interaction, the uptake of chlorhexidine base was studied from p-dioxane and it is irreversible. The uptake is total below a threshold equilibrium concentration and constant above it.
Adsorption↗
Chlorhexidine for prevention of neonatal colonization with group B streptococci. I. In vitro effect of chlorhexidine on group B streptococci.
Forty-three strains of group B streptococci (GBS) of types Ia, Ib, II and III were tested for susceptibility to chlorhexidine in concentrations ranging from 256 to 0.25 mg/l using the agar and tube dilution methods. The strains showed minimum inhibitory concentration (MIC) values ranging from 0.5 to 1 mg/l. Serum added to the test medium (50%) increased the MIC values to 4-8 mg/l, while amniotic fluid (50%) had almost no effect, increasing the values to 1-2 mg/l. The minimum bactericidal concentration (MBC) ranged from 1 to 5 mg/l. The killing kinetics were related to the concentration of chlorhexidine and the length of exposure. For example, at a concentration of 63 mg/l, 7 h were required for a bactericidal effect in broth, as compared to 1 h at 500 mg/l chlorhexidine. 200 mg/l chlordexidine had no effect on the adherence of two GBS strains to vaginal epithelial cells, and no effect on the phagocytosis of GBS with mouse peritoneal macrophages.
Bacteriolysis↗
Chlorhexidine for prevention of neonatal colonization with group B streptococci. II. Chlorhexidine concentrations and recovery of group B streptococci following vaginal washing in pregnant women.
The effect of a single washing of the urogenital tract with 0.5 g/l chlorhexidine was studied in 6 women in weeks 38-40 of pregnancy, among whom 5 were carriers of group B streptococci in urethra and/or cervix. The chlorhexidine concentrations varied between 25 and 200 mg/l during the first hour after washing in 5 of the 6 women, whereas one patient showed concentrations below 25 mg/l. With the exception of one patient, all individuals showed concentrations less than 25 mg/l at 3-24 h after washing. A clear suppression of the number of colony-forming units of GBS was already apparent after 60 min and was still evident 6 h after chlorhexidine washing.
Carrier State↗
Chlorhexidine for prevention of neonatal colonization with group B streptococci. III. Effect of vaginal washing with chlorhexidine before rupture of the membranes.
A single vaginal washing with 2 g/l of chlorhexidine was performed before rupture of the membranes in 19 parturients who were urogenital carriers of group B streptococci (GBS). Two (11%) of the infants became colonized immediately after birth, in contrast to 16 of 41 (39%) infants to controls (P = 0.02). A significant reduction of GBS colonization of the ear (P = 0.02) and umbilicus (P = 0.01) was noted. Taken together, 2 of 57 (4%) cultures obtained at birth were positive in the chlorhexidine group, in contrast to 30 of 123 (24%) among the controls (P less than 0.01). These findings raise hope for the design of a simple washing procedure which might prevent serious infections in the early neonatal period with GBS but also with other chlorhexidine-sensitive organisms.
Adolescent↗
Chlorhexidine resistance in antibiotic-resistant bacteria isolated from the surfaces of dispensers of soap containing chlorhexidine.
Bacterial contamination with pan-resistant Acinetobacter and Klebsiella, multidrug-resistant Pseudomonas, and methicillin-resistant Staphylococcus aureus (MRSA) was noted on the surfaces of dispensers of hand soap with 2% chlorhexidine. Gram-negative isolates could multiply in the presence of 1% chlorhexidine. In contrast, MRSA was inhibited in vitro by chlorhexidine at concentrations as low as 0.0019%.
Bacteria↗
Chlorhexidine for prevention of neonatal colonization with group B streptococci. IV. Depressed puerperal carriage following vaginal washing with chlorhexidine during labour.
The effect of vaginal washing with chlorhexidine acetate, 2 g/l at delivery, on the colonization of the urogenital tract with group B streptococci (GBS) 4 days later was investigated. Patients who were culture-positive for GBS in urethra and/or cervix in pregnancy weeks 32 and 36 as well as at delivery were included in a prospective study. The washing procedure was performed in 31 parturients, and 10 (32%) were culture-negative at day 4 after delivery. In contrast, only 7/47 (15%) non-washed controls were negative at day 4 (p = 0.044). The results demonstrate a prolonged suppressive effect of vaginal washing with chlorhexidine on the recovery of GBS from the urogenital tract in this highly selected patient group.
Administration, Intravaginal↗