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Formulation and in vivo evaluation of chlorhexidine buccal tablets prepared using drug-loaded chitosan microspheres.

This investigation deals with the development of buccal formulations (tablets) based on chitosan microspheres containing chlorhexidine diacetate. The microparticles were prepared by a spray-drying technique, their morphological characteristics were studied by scanning electron microscopy and the in vitro release behaviour was investigated in pH 7.0 USP buffer. Chlorhexidine in the chitosan microspheres dissolves more quickly in vitro than does chlorhexidine powder. The anti-microbial activity of the microparticles was investigated as minimum inhibitory concentration, minimum bacterial concentration and killing time. The loading of chlorhexidine into chitosan is able to maintain or improve the anti-microbial activity of the drug. The improvement is particularly high against Candida albicans. This is important for a formulation whose potential use is against buccal infections. Drug-empty microparticles have an anti-microbial activity due to the polymer itself. Buccal tablets were prepared by direct compression of the microparticles with mannitol alone or with sodium alginate. After their in vivo administration the determination of chlorhexidine in saliva showed the capacity of these formulations to give a prolonged release of the drug in the buccal cavity.

Administration, Buccal↗

Perioperative use of 0.12% chlorhexidine gluconate for the prevention of alveolar osteitis: efficacy and risk factor analysis.

OBJECTIVES: The purposes of this study were to evaluate the use of 0.12% chlorhexidine gluconate as a prophylactic therapy for the prevention of alveolar osteitis and to further examine subject-based risk factors associated with alveolar osteitis. STUDY DESIGN: The trial was a randomized, double-blind, placebo-controlled, parallel-group study conducted among 279 subjects, each of whom required oral surgery for the removal of a minimum of one impacted mandibular third molar. Subjects were instructed to rinse twice daily with 15 ml of chlorhexidine or placebo mouthrinse for 30 seconds for 1 week before and 1 week after the surgical extractions. This regimen included a supervised presurgical rinse. Alveolar osteitis diagnosis was based on the subjective finding of increasing postoperative pain at the surgical site that was not relieved with mild analgesics, supported by clinical evidence of one or more of the following: loss of blood clot, necrosis of blood clot, and exposed alveolar bone. RESULTS: In comparison with use of the placebo mouthrinse, prophylactic use of the chlorhexidine mouthrinse resulted in statistically significant (p < 0.05) reductions in the incidence of alveolar osteitis. With chlorhexidine therapy, the subject- and extraction-based incidences of alveolar osteitis in the evaluable subset (271 subjects) were reduced, relative to placebo, by 38% and 44%, respectively. The corresponding odds ratios that describe the increased odds of experiencing alveolar osteitis in the placebo group were 1.87 and 2.05 for subject- and extraction-based analyses, respectively. In comparison with nonuse of oral contraceptives, the use of oral contraceptives in female subjects was related to a statistically significant increase in the incidence of alveolar osteitis (odds ratio = 1.92, p = 0.035). Relative to male subjects, the observed incidence of alveolar osteitis for female subjects not using oral contraceptives was not statistically significant (odds ratio = 1.18, p = 0.64). Smoking did not increase the incidence of alveolar osteitis relative to not smoking (odds ratio = 1.20, p = 0.33). CONCLUSIONS: These data confirm that the prophylactic use of 0.12% chlorhexidine gluconate mouthrinse results in a significant reduction in the incidence of alveolar osteitis after the extraction of impacted mandibular third molars. In addition, oral contraceptive use in females was confirmed to be a risk factor for the development of alveolar osteitis.

Adolescent↗

Influence of ethanol with and without chlorhexidine on the bacterial colonization of the umbilicus of newborn infants.

The effect of daily treatments with 70% ethanol and with 0.5% chlorhexidine in 70% ethanol, respectively, on navel colonization in newborns has been studied in 624 infants in two maternity wards during a four-month period. Staphylococcus aureus, group B and G streptococci, E. coli and anaerobes were significantly less often isolated from newborns whose umbilical cord was treated with chlorhexidine in ethanol than from those treated with ethanol only. Staphylococcus epidermidis and enterococci, on the other hand, were significantly more often isolated from the chlorhexidine-ethanol than from the ethanol group. More infants without colonization of the umbilicus on their fourth day of life were found in the chlorhexidine in ethanol than in the ethanol group. The infants in the ethanol group were colonized with significantly more bacterial species than the infants in the other group. Signs of dissemination of group B and group G streptococci between babies were seen more often in the group of infants treated with ethanol than in the one treated with chlorhexidine-ethanol.

Chlorhexidine↗

Efficacy of chlorhexidine against some strains of cultured and clinically isolated microorganisms.

The efficacy of chlorhexidine digluconate was determined against some strains of collected and clinically isolated bacteria and fungi. The efficacy was evaluated either by calculating a minimum inhibitory concentration (MIC) or by efficacy trials according to the guidelines of the European Committee for Standardization. The MIC values of chlorhexidine for Staphylococcus aureus, Microsporum gypseum, Microsporum canis and Trichophyton mentagrophytes were 0.625 microg/ml, 12.5 microg/ml, 50 microg/ml and 6.25 microg/ml, respectively. The in vitro efficacy of chlorhexidine was higher against ATCC strains of S. aureus and P. aeruginosa (0.5 mg/ml for 5 min and 0.5 mg/ml for 10 min, respectively) than against clinical isolates (0.5 mg/ml for 15 min and 1 mg/ml for 10 min, respectively). The antiseptic activity of aqueous solutions of chlorhexidine against spores of Bacillus subtilis, Bacillis sfericus and Clostridium perfringens required longer contact times than against the vegetative forms. Nevertheless, 5 mg/ml of chlorhexidine in water-ethanol 20:80 v/v was totally effective against the vegetative forms or spores of these microorganisms.

Anti-Infective Agents, Local↗

Anaphylactic reactions in anaesthetised patients - four cases of chlorhexidine allergy.

Chlorhexidine is widely used all over the world in many different preparations. In Denmark chlorhexidine is the standard skin disinfectant used before surgery or invasive procedures and it is widely used in the general population in mouthwash or for disinfection of minor scratches etc. The potential for developing allergy to chlorhexidine is thus great, especially in surgical patients. We have identified four patients with serious allergic reactions in connection with surgery and general anaesthesia, who on subsequent skin testing tested positive for chlorhexidine. Symptoms appeared 20-40 min into the operation and all four patients required treatment with adrenaline. All four patients had a history of minor symptoms like rashes or faints in connection with previous surgery/invasive procedures. Allergy to chlorhexidine may be more prevalent in surgical patients and cases may have been overlooked due to the nature of reactions and lack of suspicion towards this substance.

Aged↗

The effects of an immediately pre-surgical chlorhexidine oral rinse on the bacterial contaminants of bone debris collected during dental implant surgery.

Dental implant surgery produces bone debris that can be used in the "simultaneous augmentation" technique. Although this debris is contaminated with oral bacteria, a stringent aspiration protocol has been shown to reduce the levels of contamination. Chlorhexidine mouthrinse is a well-proven antibacterial rinse that has been shown to reduce infectious complications associated with dental implants. This study examined the effect of pre-operative rinsing with a 0.1% chlorhexidine digluconate mouthrinse on the bacterial contaminants present in collected bone debris bone (CBD). Twenty partially edentate patients were randomly allocated into equal groups and underwent bone collection using the Frios Bone Collector (FBC) during the insertion of two dental implants. In group T a pre-operative chlorhexidine rinse was used, whilst in group C sterile water was used. For both groups, a stringent bone collection protocol was used. Bone samples were immediately transported for microbial analysis. Colonial and microscopic morphology, gaseous requirements and identification kits were utilised for identification of the isolated microbes. Thirty-nine species were identified including a number associated with disease, in particular Actinomyces odontolyticus, Clostridium bifermentans, Prevotella intermedia, and Propionibacterium propionicum. Samples from group T (chlorhexidine mouthrinse) yielded significantly fewer organisms (P < 0.001) than in group C (sterile water mouthrinse). Gram-positive cocci dominated the isolates from both groups. It is concluded that if bone debris is to be used for the purpose of immediate simultaneous augmentation, a preoperative chlorhexidine mouthrinse should be utilised in conjunction with a stringent aspiration protocol to reduce further the bacterial contamination of CBD.

Actinomyces↗

Successful medical therapy of Acanthamoeba keratitis with topical chlorhexidine and propamidine.

INTRODUCTION: Following laboratory studies on new potential chemotherapy for Acanthamoeba keratitis, when chlorhexidine and propamidine provided an additive in vitro effect, a series of 12 patients with culture-proven Acanthamoeba keratitis from three UK centres was monitored during and after therapy. METHODS: In all cases the clinical diagnosis was confirmed by amoebal culture. In some instances identification of the protozoa by direct microscopy of corneal tissue was possible. The medication was provided topically in drop form until the keratitis had resolved. In vitro sensitivity to chlorhexidine and propamidine was performed on all isolates and compared with sensitivity to a range of other drugs used for treatment of the infection. RESULTS: In vitro drug testing confirmed that trophozoites and cysts of all 12 Acanthamoeba isolates were fully sensitive to chlorhexidine and propamidine. Therapy was satisfactory for controlling and eradicating the acanthamoebal infection in all patients. Three patients developed discrete stromal infiltration at the site of infection that resolved 1 week after commencing therapy, with or without use of steroids. Two patients developed a late inflammatory effect in the stromal scar at 6 months, which resolved with steroids. No clinical evidence of chlorhexidine toxicity was found in any patients. CONCLUSIONS: The combination of topical chlorhexidine and propamidine was very effective for treating Acanthamoeba keratitis provided the drugs were continued for a sufficient period. No drug toxicity or resistance of Acanthamoeba isolates was observed in the 12 treated patients.

Acanthamoeba↗

An in vitro evaluation of the availability of cetylpyridinium chloride and chlorhexidine in some commercially available mouthrinse products.

OBJECTIVES: To assess the comparative activity of mouthrinses containing cetylpyridinium chloride (CPC) and chlorhexidine using the propensity to cause extrinsic staining in vitro as the outcome variable. METHODS: Saliva-coated clear acrylic specimens were exposed to cyclical staining regimens of either CPC or chlorhexidine followed by tea. Water and 0.2% chlorhexidine were used as negative and positive controls respectively. Staining cycles were repeated until an optical density of > 2 was reached by one of the products. RESULTS: For CPC there was a highly significant difference in staining between the products. Two CPC products performed numerically little better than water. For the chlorhexidine products the 0.2% formulation produced the most staining although little more than the UK version of the 0.1% rinse. The French 0.1% rinse produced by the same manufacturer as the UK formulation showed markedly reduced staining potential although significantly greater than water. CONCLUSION: This study, supported by previous in vitro and in vivo studies, indicates discrepancies in the availability of CPC and chlorhexidine in some mouthrinse products. Importantly, this may have an effect on the potential of some rinses to provide the expected plaque inhibitory activity.

Adsorption↗

Bond strength following the application of chlorhexidine on etched enamel.

The purpose of this study was to determine whether the application of chlorhexidine to etched enamel affects the shear bond strength and bracket/adhesive failure modes of orthodontic brackets. Forty recently extracted third molars were cleaned divided into two groups of twenty. The first group was etched with a 37% phosphoric acid gel, and a sealant was applied containing a chlorhexidine varnish. Stainless steel orthodontic brackets were bonded using the Transbond XT bonding system (3M/Unitek). Teeth in the second group were etched and bonded using the same bonding system but without chlorhexidine. A Zwick Universal Testing Machine was used to determine shear bond strengths. There were no significant differences in bond strengths between the chlorhexidine treated teeth (= 11.8 +/- 2.1 MPa) and the controls (= 12.4 +/- 3.1 MPa) (p = 0.129). The Chi Square test evaluating the residual adhesive on the enamel surfaces showed no significant differences (P = 0.136) between the two groups evaluated. The use of a primer containing chlorhexidine does not significantly affect shear bond strength nor the fracture site (bond failure location).

Acid Etching, Dental↗

The effects of adding chlorhexidine and polyhexamethylene bisguanide to a light-cured periodontal dressing material.

The effect of adding two bisguanide antimicrobial agents (chlorhexidine and PHMB) on some physical properties of the light-cured periodontal dressing material Barricaid are reported. The physical properties tested were elastic modulus, initial and 10 min recovery strains, and tear stress. The addition of both chlorhexidine and PHMB solutions reduced the elastic modulus as did water. The addition of PHMB to Barricaid produced greater initial recovery in the strain test than either the addition of chlorhexidine or water, but there were no differences between the treatments after 10 min. Tear stress was also reduced by the addition of water and the chlorhexidine and PHMB solutions. These results suggest that as far as the physical properties of Barricaid are concerned the addition of the antimicrobial agent PHMB had no long-term advantages over chlorhexidine.

Anti-Infective Agents, Local↗

Effect of sustained-release chlorhexidine varnish on Streptococcus mutans and Actinomyces viscosus in orthodontic patients.

This study evaluated the effect of sustained-release chlorhexidine varnish on orthodontic patients. Ten children, ages 10 to 16 years, participated. Bacterial levels of Streptococcus mutans and Actinomyces viscosus and total counts were evaluated in sputum samples. These counts were evaluated at 4 stages: before orthodontic treatment, at least 2 weeks after bonding of the brackets, 1 week after application of chlorhexidine varnish, and 3 weeks after application of chlorhexidine varnish. Increases in bacterial levels of S mutans and in the total bacterial count were detected after the brackets were bonded. One week after the sustained-release chlorhexidine varnish was applied, a significant decrease of total bacterial levels and S mutans was observed. This decrease persisted for 3 weeks after the first application. No significant change in A viscosus levels occurred during that period. The results provide additional evidence that sustained-release chlorhexidine varnish decreases S mutans levels in orthodontic patients with fixed appliances and therefore might be useful in preventing caries lesions.

Actinomyces viscosus↗

Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection.

A multicenter prospective, randomized, controlled trial, with 0.5% tincture of chlorhexidene versus 10% povidone-iodine as cutaneous antisepsis for central venous catheter (CVC) insertion, was conducted for patients in intensive care units. Of 374 patients, 242 had a CVC inserted for >3 days and were used for the primary analysis. Outcomes included catheter-related bacteremia, significant catheter colonization (> or = 15 colony-forming units [cfu]), exit-site infection, serial quantitative exit-site culture (every 72 h), and molecular subtyping of all isolates. Patients in both study groups were comparable with respect to age, sex, underlying disease, length of hospitalization, reason for line insertion, and baseline APACHE II score. Documented catheter-related bacteremia rates were 4.6 cases per 1000 catheter-days in the chlorhexidine group (n=125) and 4.1 cases per 1000 catheter-days in the povidone-iodine group (n=117; not significant [NS]). Significant catheter-tip colonization occurred in 24 (27%) of 88 patients in the povidone-iodine group and in 31 (34%) of 92 patients in the chlorhexidine group (NS). A mean exit-site colony count of 5.9 x 10(5) cfu/mL per 25 cm(2) of the surface area of skin in the povidone-iodine group versus 3.1 x 10(5) cfu/mL per 25 cm(2) in the chlorhexidine group (NS) was found. There was a trend toward fewer exit-site infections in the chlorhexidine group (0 of 125 patients) versus those in the povidone-iodine group (4 of 117 patients; P=.053). Results of an intention-to-treat analysis were unchanged from the primary analysis. No difference was demonstrable between 0.5% tincture of chlorhexidine and 10% povidone-iodine when used for cutaneous antisepsis for CVC insertion in patients in the intensive care unit.

Adult↗

Chlorhexidine versus povidone iodine in preventing colonization of continuous epidural catheters in children: a randomized, controlled trial.

BACKGROUND: Chlorhexidine is better than povidone iodine for skin preparation before intravascular device insertion or blood culture collection, but it is not known whether chlorhexidine is superior in reducing colonization of continuous epidural catheters. METHODS: Children requiring an epidural catheter for postoperative analgesia longer than 24 h were randomly assigned to receive skin preparation with an alcoholic solution of 0.5% chlorhexidine or an aqueous solution of 10% povidone iodine before catheter insertion. Using surgical aseptic techniques, catheters were inserted into either the lumbar or the thoracic epidural space based on the preferences of the anesthesia team, on clinical indication, or both. Immediately before epidural catheter removal, their insertion site and hub were qualitatively cultures. After their removal, the catheter tips were quantitatively cultured. Catheters were classified as colonized when their tips yielded 1,000 or more colony-forming units/ml in cultures. RESULTS: Of 100 randomly assigned patients, 96 were evaluable. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters were kept in place for a median (range) duration of 50 (range, 21-100) h. Catheters inserted after skin preparation with chlorhexidine were one sixth as likely and less quickly to be colonized as catheters inserted after skin preparation with povidone iodine (1 of 52 catheters [0.9 per 100 catheter days] vs. 5 of 44 catheters [5.6 per 100 catheter days]; relative risk, 0.2 [95% confidence interval, 0.1-1.0]; P = 0.02). Coagulase-negative staphylococci were the only colonizing microorganisms recovered, and the skin surrounding the catheter insertion site was the origin of all the colonizing microorganisms. CONCLUSIONS: Compared with aqueous povidone iodine, the use of alcoholic chlorhexidine for cutaneous antisepsis before epidural catheter insertion reduces the risk of catheter colonization in children.

Adolescent↗

A pilot study of chlorhexidine and benzydamine oral rinses for the prevention and treatment of irradiation mucositis in patients with head and neck cancer.

This pilot study was designed to compare the efficacy of 0.2% wt/vol chlorhexidine gluconate and 0.15% wt/vol benzydamine hydrochloride oral rinses in alleviating irradiation oropharyngeal mucositis for patients with head and neck cancer. This was a prospective, randomized, and double-blinded study. Fourteen subjects were stratified based on nasopharyngeal cancer and non-nasopharyngeal head and neck cancer, and were randomly assigned to receive oral care protocol either containing with chlorhexidine (n = 7) or benzydamine (n = 7) from the first day to 2 weeks after the completion of radiotherapy. Subjects were evaluated twice weekly through days 1 to 64 using the World Health Organization mucositis scale and the 10 cm visual analogue scale for mouth pain and dysphagia. In the chlorhexidine arm, 4 subjects (57%) had grade 2, and 3 subjects (43%) had grade 3 mucositis. In the benzydamine arm, 5 subjects (71%) had grade 2, and 2 subjects (29%) had grade 3 mucositis (P > .05). The mean area-under-the-curve values of mucositis were 26.5 +/- 13.6 (median 26) and 24.1 +/- 6.1 (median 22) in the chlorhexidine group and benzydamine group, respectively (P > .05). The mean area-under-the-curve values of pain and dysphagia were 70.8 +/- 33 (median 88.5) and 71.5 +/- 39 (median 101), and 62.1 +/- 17.2 (median 72) and 66 +/- 22.3 (median 57.5) in the chlorhexidine and benzydamine groups, respectively (P > .05). A trend has emerged of a lessening of severity of mucositis, pain, and dysphagia for patients with head and neck cancer receiving benzydamine oral rinse. The beneficial effects, however, need to be confirmed in a larger trial.

Adult↗

Progressive ulcerative keratitis related to the use of topical chlorhexidine gluconate (0.02%).

PURPOSE: To report a case of progressive ulcerative keratitis related to the use of topical chlorhexidine gluconate 0.02%. METHODS: A 45-year-old woman was treated for presumed Acanthamoeba keratitis with chlorhexidine gluconate 0.02% and propamidine 0.1% eyedrops. RESULTS: After using the chlorhexidine and propamidine eyedrops for 8 weeks, the patient developed a near total loss of the corneal epithelium and a progressive ulcerative keratitis, which eventually required penetrating keratoplasty. Histopathologic examination of the corneal button showed ulceration and loss of Bowman's membrane, massive loss of keratocytes with apparent apoptosis, and loss of the endothelial cells with inflammatory cells adherent to the remaining cells. These histopathologic findings are similar to those seen in Hibiclens keratopathy. Hibiclens contains chlorhexidine 4% with a detergent. No organisms were seen in sections stained with modified Ziehl-Neelsen, gram, Grocott, or periodic acid-Schiff, and immunohistochemistry showed no significant findings. CONCLUSION: We think that the topical use of chlorhexidine gluconate 0.02% may have resulted in a progressive ulcerative keratitis in our patient.

Administration, Topical↗

In vitro assessment of the antimicrobial action and the mechanical ability of chlorhexidine gel as an endodontic irrigant.

The objective of this study was to assess the chlorhexidine gluconate gel as an endodontic irrigant. First the ability of chlorhexidine gel to disinfect root canals contaminated in vitro with Enterococcus faecalis was investigated. A scanning electron microscope was also used to evaluate its cleansing ability compared with endodontic irrigants commonly used, such as sodium hypochlorite and chlorhexidine gluconate liquid. The results indicated that the chlorhexidine gel produced a cleaner root canal surface and had an antimicrobial ability comparable with that obtained with the other solutions tested. It was concluded that chlorhexidine gluconate in gel form has potential for use as an endodontic irrigant.

Anti-Infective Agents, Local↗

In situ antimicrobial effectiveness of chlorhexidine and calcium hydroxide: gel and paste versus gutta-percha points.

The aim of this study was to determine the antibacterial effectiveness of either chlorhexidine or calcium hydroxide integrated in gutta-percha points compared with chlorhexidine or calcium hydroxide delivered as gel or paste, respectively. A total of 70 initially sterile roots with open accesses were carried for 1 week in the oral cavities of two volunteers. The roots were then removed, and samples were taken from the root canals for microbial analysis. The roots were medicated with calcium hydroxide paste, 5% chlorhexidine gel, or a chlorhexidine- or calcium hydroxide-containing gutta-percha point. The accesses were closed with bonding material, and the roots incubated for 1 week. After removal of the antimicrobial agents, roots were again checked for bacterial growth. One thioglycolate-soaked paper point was then introduced into each canal, and roots were incubated for 1 week more to observe bacterial regrowth. After 1 week of medication, the absolute bacterial count revealed significant differences compared with the controls. However, only the chlorhexidine-gel and the calcium hydroxide paste group showed no microbial colonization in a considerable number of samples after 1 and 2 weeks.

Anti-Infective Agents, Local↗

Comparison of 10% povidone-iodine and 0.5% chlorhexidine gluconate for the prevention of peripheral intravenous catheter colonization in neonates: a prospective trial.

The purpose of the study was to compare the efficacy of 10% povidone-iodine with that of 0.5% chlorhexidine gluconate in 70% isopropyl alcohol for the prevention of peripheral intravenous catheter colonization in neonates. This was a multicenter, nonrandomized prospective study in a tertiary neonatal intensive care setting in which povidone-iodine and chlorhexidine gluconate were each used as antiseptic skin preparations over sequential 6-month periods. During the first 6 months of the study when povidone-iodine was in use 9.3% (38 of 408) of catheters were colonized. During the second 6 months of the study when chlorhexidine gluconate was in use, catheter colonization occurred in 4.7% (20 of 418, P = 0.01). Catheter-related bacteremia occurred during only 0.2% (2 of 826) of all catheterizations. Heavy skin colonization before catheter insertion (relative risk, 3.6; 95% confidence interval, 1.9, 7.0), catheterization > or = 72 hours (relative risk. 2.0; 95% confidence interval, 1.01, 3.8) and gestational age < or = 32 weeks (relative risk, 1.8; 95% confidence interval, 1.02, 3.3) increased colonization risk. Ampicillin infusion (relative risk, 0.4; 95% confidence interval, 0.2, 0.7) and 0.5% chlorhexidine gluconate cutaneous antisepsis (relative risk, 0.4; 95% confidence interval, 0.2, 0.8) were factors associated with decreased colonization risk. We conclude that 0.5% chlorhexidine gluconate in 70% isopropyl alcohol appears to be more efficacious than 10% povidone-iodine for the prevention of peripheral intravenous catheter colonization in neonates.

Analysis of Variance↗