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PubMed1999

Chlorhexidine-induced changes to human gingival fibroblast collagen and non-collagen protein production.

BACKGROUND: Chlorhexidine (CHX) has been used extensively as an adjunctive therapy in the treatment of periodontal disease. It is well known that chlorhexidine is toxic to bacteria, but recent evidence has suggested that chlorhexidine may also have deleterious effects on gingival fibroblast proliferation as well as collagen and non-collagen protein production in cell culture. The purpose of this study was to examine the effects of chlorhexidine on gingival fibroblast proliferation as well as collagen and non-collagen protein production in cell culture. METHODS: Human gingival fibroblasts were incubated in MEM containing chlorhexidine concentrations ranging from 1 microM to 1300 microM at 37 degrees C for 1, 5, or 15 minutes. Control cells received an equal volume of MEM without chlorhexidine for similar times at 37 degrees C. Following incubation, the media were removed, cells washed twice with MEM supplemented with 10% FBS, and fibroblasts in treatment and control groups were allowed to recover in the same media for 24 hours. RESULTS: In all strains, cellular proliferation was dependent on the concentration of solubilized chlorhexidine in cell culture but independent of the duration of chlorhexidine exposure. The average inhibitory concentration necessary to reduce cellular proliferation by 50% (ID50) was 222.1 microM. In regard to collagen and non-collagen protein production, fibroblasts exposed to chlorhexidine concentrations (1 microM) well below the ID50 had a 65% reduction in collagen production and a 57% reduction in noncollagen protein production. CONCLUSIONS: These results suggest that chlorhexidine will induce a dose dependent reduction in cellular proliferation and that concentrations of chlorhexidine that have little effect on cellular proliferation can significantly reduce both collagen and noncollagen protein production of human gingival fibroblasts in vitro. Hence, the introduction of commercially available concentrations (0.12%) or diluted commercial concentrations (as low as 0.00009%) of chlorhexidine to surgical sites for short periods of time prior to wound closure can conceivably have serious toxic effects on gingival fibroblasts and may negatively affect wound healing.

Anti-Infective Agents, Local↗

PubMed2003

Is there a risk of sensitization and allergy to chlorhexidine in health care workers?

BACKGROUND: In Denmark, chlorhexidine is the standard disinfectant in most hospitals and health care workers are repeatedly exposed to it. The aim of this study was to establish whether there is a risk of sensitization and allergy to chlorhexidine from this type of exposure. METHODS: Two hundred and forty-eight doctors, nurses and auxiliary staff were invited to participate in the study. One hundred and four individuals took part in the full study including skin tests and a questionnaire and a further 74 individuals filled in the questionnaire giving a total of 178 questionnaires (72%). Patch tests with chlorhexidine gluconate 1% and chlorhexidine acetate 1% were performed looking for type IV (delayed type) allergy. A prick test with chlorhexidine gluconate 0.5% and an intradermal test with chlorhexidine 0.0002% were performed looking for type I (immediate type) allergy. RESULTS: There were no positive tests in any of the 104 individuals tested (99% confidence interval 0-4.9%). There was a predominance of females in both groups and the overall median age was 42 years (28-63). No one in the group not tested reported to have a verified or suspected allergy to chlorhexidine. CONCLUSION: In this first study to examine the risk of type I and type IV allergy to chlorhexidine in health care workers with daily exposure to chlorhexidine, we did not identify allergies to chlorhexidine in any of the 104 individuals tested or in the additional 74 individuals who completed the questionnaire. We conclude that an allergy to chlorhexidine in health care workers is likely to be rare.

Adult↗

PubMed2002

Chlorhexidine vaginal flushings versus systemic ampicillin in the prevention of vertical transmission of neonatal group B streptococcus, at term.

OBJECTIVE: To investigate the efficacy of intrapartum vaginal flushings with chlorhexidine compared with ampicillin in preventing group B streptococcus transmission to neonates. METHODS: This was a randomized controlled study, including singleton pregnancies delivering vaginally. Rupture of membranes, when present, must not have occurred more than 6 h previously. Women with any gestational complication, with a newborn previously affected by group B streptococcus sepsis or whose cervical dilatation was greater than 5 cm were excluded. A total of 244 group B streptococcus-colonized mothers at term (screened at 36-38 weeks) were randomized to receive either 140 ml chlorhexidine 0.2% by vaginal flushings every 6 h or ampicillin 2 g intravenously every 6 h until delivery. Neonatal swabs were taken at birth, at three different sites (nose, ear and gastric juice). RESULTS: A total of 108 women were treated with ampicillin and 109 with chlorhexidine. Their ages and gestational weeks at delivery were similar in the two groups. Nulliparous women were equally distributed between the two groups (ampicillin, 87%; chlorhexidine, 89%). Clinical data such as birth weight (ampicillin, 3,365 +/- 390 g; chlorhexidine, 3,440 +/- 452 g), Apgar scores at 1 min (ampicillin, 8.4 +/- 0.9; chlorhexidine, 8.2 +/- 1.4) and at 5 min (ampicillin, 9.7 +/- 0.6; chlorhexidine, 9.6 +/- 1.1) were similar for the two groups, as was the rate of neonatal group B streptococcus colonization (chlorhexidine, 15.6%; ampicillin, 12%). Escherichia coli, on the other hand, was significantly more prevalent in the ampicillin (7.4%) than in the chlorhexidine group (1.8%, p < 0.05). Six neonates were transferred to the neonatal intensive care unit, including two cases of early-onset sepsis (one in each group). CONCLUSIONS: In this carefully screened target population, intrapartum vaginal flushings with chlorhexidine in colonized mothers display the same efficacy as ampicillin in preventing vertical transmission of group B streptococcus. Moreover, the rate of neonatal E. coli colonization was reduced by chlorhexidine.

Administration, Intravaginal↗

PubMed1994

Comparison of 2 chlorhexidine mouthwashes on plaque regrowth in vivo and dietary staining in vitro.

Until recently, the few available chlorhexidine mouthrinse products have been 0.2% formulations. However, concentrations of 0.12% chlorhexidine appear as effective as 0.2%, if the volume of the rinse is increased to 15 ml. Since the mere incorporation of chlorhexidine in a formulation does not guarantee availability of the antiseptic, it would seem reasonable to evaluate or compare all products. This is particularly the case when other ingredients, such as fluoride are added. The 1st study compared the effect of a 0.12% chlorhexidine rinse with a 0.12% chlorhexidine/0.022% sodium fluoride rinse for effects on plaque regrowth. The study was a 7-day, blind, randomised, 2-cell cross-over design with a baseline control run in period, in which 18 subjects participated. Both chlorhexidine products significantly reduced plaque compared to control but the chlorhexidine fluoride rinse was less effective than the chlorhexidine only rinse. The 2nd study assessed the propensity of the chlorhexidine rinses to induce dietary staining in vitro. For the chlorhexidine fluoride rinse, this was less than the other 0.12% rinse and a commonly used 0.2% product. The data in vivo and in vitro suggest reduced chlorhexidine availability from the chlorhexidine fluoride product which appears to cause some loss of efficacy.

Chlorhexidine↗

PubMed1991

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↗

PubMed2000

Stain, plaque and gingivitis reduction by combining chlorhexidine and peroxyborate.

BACKGROUND: Previous studies have shown that using an oxidising agent in addition to chlorhexidine reduces staining. AIM: The purpose of the present study was to investigate whether, compared to chlorhexidine alone, the use of an oxidising mouthrinse as an adjunct to chlorhexidine is efficacious in reducing stain, plaque and gingivitis. METHOD: This study had a single-blind, 2-group parallel design, including a 14-day experimental non-brushing period during which 1 group (n= 14) used chlorhexidine alone (CHX) (chlorhexidine mouthrinse, 0.12% Oral-B laboratories, Ireland), and the other (n= 14) used chlorhexidine in combination with an oxidising agent (sodiumperborate-monohydrate-Bocasan, Oral-B laboratories, Ireland). Patients were randomly assigned to either group. All participants received a scaling and polishing before the start of the trial. No oral hygiene instructions were given. Since, at the start of the experiment, all stain and plaque were removed, only the gingival condition was evaluated at baseline by means of bleeding on marginal probing. The examination after 14 days of rinsing included the evaluation of plaque, bleeding on marginal probing and stain (GMSI: gingival modification of the stain index). RESULTS: The results showed at day 14, a significant difference between the 2 groups for plaque (CHX: 0.18, CHX+PER: 0.08, p=0.03) and gingival bleeding (CHX: 0.38, CHX+PER: 0.21, p<0.001). The proportion of stained surfaces was less in the CHX+PER group (28%), than in the chlorhexidine group (48%) (p=0.04). CONCLUSIONS: In conclusion, the adjunctive use of an oxidising agent peroxyborate to chlorhexidine, proved to be superior to chlorhexidine alone with regard to the inhibition of plaque and development of gingivitis. In addition, the proportion of stained surfaces was significantly less when adding the oxidising mouthrinse to chlorhexidine.

Adult↗

PubMed2003

Do cancer patients with chemotherapy-induced leukopenia benefit from an antiseptic chlorhexidine-based oral rinse? A double-blind, block-randomized, controlled study.

Patients undergoing cancer chemotherapy frequently suffer from mucositis, particularly if they become leukopenic (leucocytes <1000/microL). To identify a possible benefit from antiseptic rinsing of the oral cavity, 47 patients were randomized to rinse either with a chlorhexidine-based product (chlorhexidine concentration 0.3%; N=24) or with an amine-stannous fluoride combination (control group; N=23). Patients were asked to rinse three times a day for 30s from the beginning of chemotherapy until the end of leukopenia. Before rinsing, as well as during and after leukopenia, aerobic and anaerobic bacteria in the oral cavity were counted. At the same time, the patients were assessed for mucositis. In the chlorhexidine-based group, a significant decrease of the aerobic (P=0.042) and anaerobic (P=0.008) bacterial flora was identified. In the control group, the numbers of aerobic and anaerobic bacteria remained unchanged (P>0.05). Fifteen patients in the chlorhexidine-based group had a C-reactive protein (CRP) increase >50mg/L, compared with only eight patients in the control group [odds ratio: 3.13, confidence interval (CI) 0.82-12.39]. Nine patients in the chlorhexidine-based group but only two patients in the control group developed severe mucositis. This difference was statistically significant with an odds ratio of 6.30 (CI: 1.02-49.67). As not all of the 47 patients developed severe leukopenia, a separate analysis was carried out for patients with <1000 leucocytes/microL for a minimum of three days. The results of the microbial counts were very similar, with a clear reduction in the chlorhexidine group and no major alterations in the control group. Twelve of 15 patients in the chlorhexidine-based group had a CRP >50mg/L whereas only eight of 15 patients did so in the control group, which can be regarded as a slightly elevated risk for a CRP increase in the former group. Seven of 15 patients developed severe mucositis in the chlorhexidine-based group, but only two of 15 patients in the control group. These differences were not significant, but patients treated with chlorhexidine-based product seemed to have more problems with inflammation of the oral mucous membranes, resulting in an elevated mucositis score and a CRP increase. Other parameters such as body temperature or application of antibiotics did not differ between the two groups. We conclude that treatment with the chlorhexidine-based product did not provide a clinical benefit for cancer chemotherapy patients. On the contrary, the risk of mucositis and clinical sequelae seems to be enhanced, although the counts of micro-organisms on the oral mucous membranes are significantly reduced.

Adolescent↗

PubMed2004

Cost-benefit analysis of chlorhexidine gluconate dressing in the prevention of catheter-related bloodstream infections.

OBJECTIVES: To compare the costs with the benefits of using chlorhexidine gluconate dressings on central venous catheters and to determine the effectiveness of these dressings in reducing local infections and catheter-related bloodstream infections (CRBSIs), costs, and mortality. DESIGN: Cost-benefit analysis using randomized, controlled trial data on chlorhexidine dressing prevention of local infection and CRBSI, data on cost of chlorhexidine dressing versus standard treatment, data on averted cost of treating local infection and CRBSI, and data on mortality attributable to CRBSI. Decision analysis evaluated averted CRBSI treatment cost per patient resulting from chlorhexidine dressing use. Sensitivity analyses demonstrated net benefit of chlorhexidine dressing, varying baseline rate of CRBSI, incremental cost of treating CRBSI, and number of catheters, and evaluated mortality preventable through chlorhexidine dressing use, varying baseline rate of CRBSI, number of catheters, and mortality attributable to CRBSI. PATIENTS AND SETTING: Patients of all Philadelphia area hospitals and one Philadelphia academic medical center. RESULTS: Estimated potential annual U.S. net benefits from chlorhexidine dressing use ranged from $275 million to approximately $1.97 billion. Cost-benefit findings persisted in sensitivity analyses varying baseline rate of CRBSI, incremental cost of treating CRBSI, and overall number of catheters used. Preventable mortality analyses showed potential decreases of between 329 and 3,906 U.S. deaths annually as a result of nationwide use of chlorhexidine dressing. CONCLUSIONS: Chlorhexidine dressings would reduce costs, local infections and CRBSIs, and deaths. Use of chlorhexidine dressings should be considered to prevent infections among patients with catheters.

Anti-Infective Agents, Local↗

PubMed1986

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↗

PubMed1991

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↗

PubMed1992

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↗

PubMed1998

The effect of nonoxynol-9 and chlorhexidine on HIV and sperm in vitro.

The effect of chlorhexidine and nonoxynol-9, either singly or in combination, on the replication and infectivity of HIV and the survival of both lymphocytes (MT2 cells) and human spermatozoa, was studied in vitro. Exposure of MT2 cells to 200 microg/ml nonoxynol-9 or 1 mg/ml chlorhexidine for one minute destroyed their viability. A combination of 60 microg/ml of nonoxynol-9 and chlorhexidine, however, killed MT2 cells under the same conditions. Nonoxynol-9 and chlorhexidine were both spermicidal, 268 microg/ml nonoxynol-9, or 2.063 mg/ml chlorhexidine caused complete immobilization of sperm after one minute. The same effect was achieved by a combination of 200 microg/ml nonoxynol-9 and 1.0 mg/ml chlorhexidine. The effect of chlorhexidine and nonoxynol-9 on the replication of HIV was estimated by the output of p24 (the HIV core protein) and the concentration of virus was determined by titration with MT2 cells. Separately, 300 microg/ml nonoxynol-9 alone completely inactivated HIV, while 1 mg/ml chlorhexidine was 80%-100% effective. Certain combinations of nonoxynol-9 and chlorhexidine were antagonistic in their inactivation of HIV, up to 400 microg/ml chlorhexidine partly neutralized the action of 200-500 microg/ml nonoxynol-9.

Anti-HIV Agents↗

PubMed2003

Attachment of periodontal ligament cells to chlorhexidine-loaded guided tissue regeneration membranes.

BACKGROUND: Early exposure of a guided tissue regeneration (GTR) membrane in the oral cavity results in bacterial contamination, which may lead to failure or incomplete regeneration. Incorporation of antimicrobial agents in GTR membranes may be valuable to control membrane-associated infection during GTR therapy. The purpose of this study was to evaluate whether the incorporation of chlorhexidine into various GTR membranes improves the attachment of periodontal ligament cells in the presence of Actinobacillus actinomycetemcomitans. METHODS: The possible effects of chlorhexidine on the viability of primary human periodontal ligament (PDL) cells were determined using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT), which measures cellular metabolic activity. An expanded polytetrafluoroethylene (ePTFE) membrane, glycolide fiber membrane, and collagen membrane were loaded with chlorhexidine and characterized. Attachment of PDL cells to the chlorhexidine-loaded membranes with or without A. actinomycetemcomitans was examined using scanning electron microscopy (SEM) analysis. RESULTS: Relative cellular viability of PDL cells was reduced to approximately 50% when 15 microg/ml (0.0015%) of chlorhexidine was used. Chlorhexidine released from the coated GTR membranes inhibited the growth of A. actinomycetemcomitans. At the concentration used in this study, chlorhexidine incorporated into the GTR membranes did not interfere with the attachment of PDL cells. The inhibitory effects of A. actinomycetemcomitans on cellular attachment were reduced using chlorhexidine-loaded membranes, including ePTFE, glycolide fiber, and collagen membranes. CONCLUSIONS: These results suggest that incorporation of chlorhexidine into GTR membranes is beneficial in reducing bacterial effects on cellular attachment. The future application of chlorhexidine-loaded membranes during GTR therapy may be of value.

Absorbable Implants↗

PubMed2003

Elimination kinetics of chlorhexidine in milk following intramammary infusion to stop lactation in mastitic mammary gland quarters of cows.

OBJECTIVE: To evaluate the elimination kinetics of chlorhexidine in milk when used as an intramammary infusion to stop lactation in cows. DESIGN: Prospective study. ANIMALS: 6 cows. PROCEDURE: The study was performed in 2 phases. Three cows were studied in each phase. All cows were treated with chlorhexidine suspension by infusion into a mastitic mammary gland quarter after 2 milkings 24 hours apart. Foremilk samples (100 mL) were collected from treated and untreated (controls) mammary gland quarters of each cow. Chlorhexidine was extracted from raw milk, and residue concentrations were quantified by use of high-performance liquid chromatography. Foremilk samples from days 2, 5, and 8 were analyzed in phase I, and samples from time 0 and days 3, 7, 14, 21, 28, 35, and 42 were analyzed in phase II. RESULTS: In phases I and II, there was no quantifiable transference of chlorhexidine to milk in untreated mammary gland quarters. Measurable chlorhexidine residues were found in milk from treated mammary gland quarters of 2 cows throughout the 42-day sample period in phase II. Estimated mean elimination half-life for chlorhexidine in milk was 11.5 days. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of the long elimination half-life of chlorhexidine in milk from treated mammary gland quarters, the lack of human dietary exposure data to suggest a food tolerance for chlorhexidine in food products, and the Food and Drug Administration's published zero tolerance for chlorhexidine in uncooked edible calf tissues, we do not recommend extralabel use of chlorhexidine suspension as a treatment to stop lactation in mastitic mammary gland quarters of cows.

Animals↗

PubMed2004

Increased postoperative peritoneal adhesion formation after the treatment of experimental peritonitis with chlorhexidine.

BACKGROUND AND AIMS: Chlorhexidine is known as a substance that produces adhesions. However, in an experimental model of peritoneal injury, lavage with chlorhexidine and saline solutions produced a similar number of adhesions. This study was designed to test the hypothesis that chlorhexidine gluconate 0.05% solution used for the treatment of peritonitis increases formation of postoperative peritoneal adhesions as compared to standard lavage with saline solution. MATERIAL AND METHODS: Forty Wistar rats were randomly allocated to gastric or faecal peritonitis groups. In each group rats were further randomly subdivided into saline or chlorhexidine peritoneal lavage groups. After 30 days the rats were killed and intraperitoneal adhesions were evaluated by adhesion score and grading. RESULTS: Adhesion scores were statistically significantly different between saline and chlorhexidine groups in both gastric and faecal peritonitis models. In the faecal peritonitis chlorhexidine group a 20% small bowel intussusception rate was observed, while there were no such complications in the other study groups. The conglomerate of organs formed by dense adhesions was present in 60% of cases when gastric peritonitis was lavaged by chlorhexidine and in only 10% when saline solution was used ( P<0.05). Neither chlorhexidine nor saline solutions have caused such dense adhesions in faecal peritonitis. CONCLUSION: Peritoneal lavage with chlorhexidine gluconate 0.05% solution in the treatment of experimental peritonitis results in increased adhesion formation.

Animals↗

PubMed1987

Factors influencing the immunogenicity of the haptenic drug chlorhexidine in mice--Part I. Molecular requirements for the induction of IgE and IgG anti-hapten antibodies.

The immunogenicity of a novel hapten, the anti-microbial agent, chlorhexidine (1,1'-hexamethylene bis [5-(p-chlorophenyl)biguanide]) was assessed in mice, using alum as adjuvant. The i.p. injection of electrostatically-linked chlorhexidine + keyhole limpet haemocyanin (KLH) mixtures induced low level primary IgG anti-chlorhexidine antibody synthesis. In contrast, covalently-linked chlorhexidine-KLH complexes induced both IgE and IgG anti-chlorhexidine antibody synthesis. Covalent binding was facilitated by the N-chlorination of secondary amide groups on the biguanide moeities of the chlorhexidine molecule. The immunogenicity of such complexes was related to the degree of conjugation of chlorhexidine to KLH; which, in turn, was related to the molarity of chlorine used to effect N-chlorination. Immune responses to covalently-linked complexes could be enhanced by carrier priming. The induction of low levels of IgG anti-hapten antibodies by electrostatically-linked complexes may reflect T cell-independent specific B cell activation, either by chlorhexidine itself or by a "pseudo-plurivalent" chlorhexidine + KLH antigen.

Animals↗

PubMed2001

The effect of polyvinyl pyrrolidone on the clinical activity of 0.09% and 0.2% chlorhexidine mouthrinses.

BACKGROUND: Previous studies have shown that polyvinyl pyrrolidone (PVP) added to a chlorhexidine rinse reduced extrinsic dental stain but at the expense of a reduction in plaque inhibitory activity. This effect appeared due to a reduction in the effective chlorhexidine dose to levels where dose response studies show plaque inhibition falls off rapidly. The aim of these 2 clinical studies was to determine if PVP could be added to chlorhexidine rinses to maintain efficacy and reduce staining. METHOD: Study 1 involved 42 healthy dentate volunteers and was a blind, randomised, 7 treatment, crossover design balanced for residual effects. The rinses were: 1. 0.09% chlorhexidine to which was added, 2. 1% PVP, 3. 3% PVP, 4. 5% PVP, 5. 7% PVP, 6. Placebo, 7. Essential oil product. Rinses were used 2x on day one of each period after a prophylaxis. Subjects suspended tooth cleaning for 24 h and were then scored for plaque area. Study 2 used the experimental gingivitis model, involved 24 healthy dentate subjects and was a blind, randomised, 3 treatment, crossover design balanced for residual effects. The rinses were 1. 0.2% chlorhexidine, 2. 0.2% chlorhexidine/10% PVP, 3. Placebo. At baseline and the end of each study period subjects were rendered plaque, stain and calculus free, suspended oral hygiene and rinsed 2x per day. Plaque, gingivitis and stain were scored at baseline, 1, 2, and 3 weeks. Calculus was scored at baseline and 3 weeks. RESULTS: Study 1: Buccal plaque scores were significantly lower with all rinses compared to placebo. Also all buccal plaque scores were significantly lower with chlorhexidine and chlorhexidine/PVP rinses compared to the essential oil/phenolic rinse. There were no significant differences between the chlorhexidine rinse and the chlorhexidine/PVP rinses. Analyses for buccal and lingual plaque combined produced, with one exception, the same results for rinse comparisons as for buccal plaque alone. Thus the essential oil/phenolic rinse just failed to reach significance compared to placebo. Study 2: Plaque and gingivitis scores were significantly lower with positive control and test rinses compared to placebo but with no difference between these rinses. Tooth and tongue stain was significantly higher with the positive control and test rinses compared to placebo but not significantly different between these 2 rinses. Calculus scores were not significantly different between the three study rinses. CONCLUSION: Taken with previous data, the balance of evidence does not support PVP as an inhibitor of staining associated with chlorhexidine. These data are further evidence that chlorhexidine oral hygiene products, which, do not or claim not to cause staining, are most probably lacking efficacy.

Adult↗

PubMed2001

Reduction of saltiness and bitterness after a chlorhexidine rinse.

Chronic rinsing with chlorhexidine, an oral-antiseptic, has been shown to decrease the saltiness of NaCl and the bitterness of quinine. The effect of acute chlorhexidine on taste has not been investigated. The purpose of the present study was to examine the effect of acute chlorhexidine rinses on taste intensity and quality of 11 stimuli representing sweet, salt, sour, bitter and savory. All stimuli were first matched for overall intensity so the effects of chlorhexidine would be directly comparable across compounds. As a control treatment, the bitter taste of chlorhexidine digluconate (0.12%) was matched in intensity to quinine HCl, which was found to cross-adapt the bitterness of chlorhexidine. Subjects participated in four experimental conditions: a pre-test, a quinine treatment, a chlorhexidine treatment, and a post-test condition, while rating total taste intensity and taste qualities in separate test sessions. Relative to the quinine treatment, chlorhexidine was found to decrease the salty taste of NaCl, KCl and NH4Cl, and not to significantly affect the tastes of sucrose, monosodium glutamate (MSG), citric acid, HCl and the taste of water. The bitter taste of urea, sucrose octa-acetate and quinine were suppressed after chlorhexidine rinses relative to water rinses, but were only marginally suppressed relative to quinine rinses. Potential mechanisms are discussed.

Adult↗