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↗
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↗
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↗
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↗
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 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↗
[Evaluation of semiannual combined-treatment with fluoride-chlorhexidine varnish and toothbrushing with chlorhexidine toothpaste for 15 days every 3 months in hypercariogenic children].
An investigation was carried out in hypercaries-producing children, who had have previously curative treatment. Twenty three children were treated with semestral applications of fluorine-chlorhexidine varnish and daily brushing for 15 days every three months, with dental creme with chlorhexidine, while 21 children were selected as control group. Four analysis of Str. mutants in saliva (Matsukubo technique) were performed to each child in both groups, during a year. It was found that children treated reduced, remarkably, the degree of infection by Str. mutans, while degree of infection did not suffer modification in those children of the control group. The final examination performed after one year showed that 15 children of the control group resulted affected by caries (71.4%) with an incidence of 27 caries (1.29 index), while in the group under treatment only a child resulted affected with a caries. Reduction found in the incidence of caries was 96.9%. Problematic of hypercaries-producing child is analyzed and it is concluded that it is necessary to control and record him, and that investment in a strict treatment, such as that successfully assayed by us, should be rentable, since it should reduce amount of extractions of teeth and to contribute in that way to a real promotion of oral health with the infantile population.
Child↗
Extrinsic tooth discoloration by metals and chlorhexidine. II. Clinical staining produced by chlorhexidine, iron and tea.
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Adult↗
Blood concentrations of chlorhexidine in neonates undergoing routine cord care with 4% chlorhexidine gluconate solution.
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Chlorhexidine↗
Chlorhexidine gluconate and acetate in patch testing.
Patch testing to chlorhexidine is usually performed with chlorhexidine gluconate aq. We report the results of 297 patients, almost all with leg ulcers, concomitantly tested with chlorhexidine acetate 1% aq. and chlorhexidine gluconate 1% aq. 39 patients had positive reactions to one of these compounds or to both. 36 positive reactions to the acetate were found, in contrast to 18 reactions to the gluconate. The reactions were considered relevant in 22 of 39 patients, since these patients had developed an eczema in an area where a chlorhexidine compound was used, and discontinuing the chlorhexidine compound resulted in improvement of the condition. In 10 of these 22 patients, the diagnosis would have been missed if the gluconate only had been used for testing, while the acetate failed to diagnose 2 patients. In 109 patients without leg ulcers, inconclusive patch test readings (i.e., irritant reactions or weak positive reactions) were found in 17% with chlorhexidine acetate 1% aq., compared to 5% with chlorhexidine gluconate 1% aq., indicating a high degree of irritant potential of the acetate 1% aq. We consider that some positive reactions are lost if chlorhexidine gluconate 1% aq. only is used for patch testing, but that chlorhexidine acetate 1% aq., on the other hand, is an unacceptably strong irritant. We therefore suggest that further testing with chlorhexidine acetate 1 and 0.5% aq. should be performed, in parallel with chlorhexidine gluconate 1% aq., in order to establish appropriate test concentrations. We find that up to 13% of the leg ulcer patients in this study may be sensitized to chlorhexidine, and we recommend that the indications for the drug in leg ulcer patients should be reconsidered.
Chlorhexidine↗
Chlorhexidine resistance in methicillin-resistant Staphylococcus aureus or just an elevated MIC? An in vitro and in vivo assessment.
Chlorhexidine (Hibiscrub; ICI) is generally accepted to be effective as an antiseptic hand wash for methicillin-susceptible Staphylococcus aureus (MSSA), but there is dispute whether the chlorhexidine MIC for methicillin-resistant S. aureus (MRSA) strains is higher than that for MSSA strains and, indeed, whether it is relevant. In addition, the link between resistance to chlorhexidine, gentamicin, and "nucleic acid-binding" compounds (NAB; which code, in particular, for propamidine isethionate and ethidium bromide) requires clarification. We performed chlorhexidine MIC and rate of kill tests on a number of MSSA and MRSA isolates. Two gentamicin-resistant MRSA isolates without NAB plasmids were more susceptible (0.25 and 0.5 microgram/ml) than four of eight MSSA that we tested (range, 0.25 to 2 microgram/ml). Chlorhexidine MICs were higher (4 to 8 micrograms/ml) for seven distinct MRSA isolates with plasmids conveying resistance to gentamicin and NAB (GNAB). Curing of the GNAB plasmid from MRSA strains resulted in a fall in the MIC (1 to 3.3 micrograms/ml), but no consistent fall in killing by chlorhexidine was observed. No effect on the chlorhexidine MIC or killing was observed when we cured strains of methicillin resistance. GNAB plasmid transfer resulted in a rise in the chlorhexidine MIC for the strains but not consistent fall in killing by chlorhexidine. Ethical approval was granted for 10 volunteers to each have a methicillin-susceptible, GNAB-resistant, derived transcipient and its GNAB-susceptible isogenic parent applied to separate sites in an in vivo skin test; no significant difference was seen in survival rates after the application of chlorhexidine. These results suggest that chlorhexidine appears to be as effective as a hand-washing agent for MRSA isolates with or with out NAB plasmids as it is for MSSA isolates.
Chlorhexidine↗
IgE antibody-mediated shock reaction caused by topical application of chlorhexidine.
A case of an anaphylactic shock following topical application of chlorhexidine preparation is reported. Specific skin-sensitizing antibodies against chlorhexidine were demonstrated in the serum from the patient by a passive transfer test. IgE antibodies against chlorhexidine were also detected by radioallergosorbent technique (RAST). Paper discs conjugated with chlorhexidine-HSA (human serum albumin) significantly bound the IgE antibodies. Furthermore, all of the sera from seven other patients with shock reactions following the topical application of chlorhexidine preparation also showed high RAST counts. Both chlorhexidine gluconate and chlorguanide which represents approximately half a molecule of chlorhexidine inhibited the reaction in a dose-dependent fashion. It is suggested that the shock reactions following topical application of chlorhexidine are mediated by IgE antibodies against chlorhexidine and that chlorhexidine and chlorguanide share the same antigenic determinant.
Administration, Topical↗
Determination of chlorhexidine in saliva and in aqueous solutions.
A new method is presented for the determination of chlorhexidine in centrifuged saliva and in aqueous solutions by means of fluorescence spectroscopy. The method relies on complex formation between chlorhexidine and eosin. The fluorescence value of the chlorhexidine-eosin system decreases with increasing chlorhexidine concentrations. In centrifuged saliva a linear relation was found between the fluorescence at 541 nm and the chlorhexidine content up to about 15 ppm; the reproducibility of the method was found to be better than 1 ppm chlorhexidine. The biological spreading for centrifuged saliva from different participants as well as the spreading due to the period of saliva collection are about 3%. In whole uncentrifuged saliva the fluorescence method has been a detection limit of about 8 ppm chlorhexidine, due to the binding of the compound to salivary constituents. Above 8 ppm chlorhexidine, the biological variation in saliva is such that chlorhexidine determinations by means of fluorescence can be done only with a reproducibility of +/- 10 ppm. Advantages and disadvantages of the ultraviolet spectroscopy method, the radioactive labelling technique, and the fluorescence method for chlorhexidine determinations are discussed.
Centrifugation↗
Effects of chlorhexidine-containing gel and varnish on abutment teeth in patients with overdentures.
Previous experiments have shown that daily use of 1% chlorhexidine gel strongly reduced caries development in the abutment teeth under overdentures. The present experiment was designed to determine whether intermittent application of chlorhexidine, either in a varnish or in a gel, might be used as an alternative preventive method, less demanding for the patient. To this end, 31 patients were distributed among four treatment groups, with the number of mutans streptococci in plaque and saliva used as a balancing criterion. The treatments consisted of a single application of 40% chlorhexidine varnish, daily application of 1% chlorhexidine gel for one week, or the corresponding placebo treatments with varnish or gel without chlorhexidine. Patients were re-called for bacteriological and clinical examination at various intervals during an eight-week period following treatment. Chlorhexidine varnish and chlorhexidine gel applications significantly suppressed mutans streptococci on the abutment teeth for four and eight weeks, respectively. In agreement with earlier findings, the numbers of Actinomyces viscosus/naeslundii in plaque were significantly increased after chlorhexidine varnish treatment. The chlorhexidine gel reduced plaque accumulation and gingival bleeding for one week but had no long-lasting effect. The results seem to justify a long-term clinical test of intermittent chlorhexidine applications as an alternative for daily use in patients with overdentures.
Analysis of Variance↗