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Chlorhexidine prophylaxis for chemotherapy- and radiotherapy-induced stomatitis: a randomized double-blind trial.

Patients receiving cytotoxic antineoplastic therapy often have treatment-associated stomatitis. A 0.12% chlorhexidine digluconate mouthrinse was evaluated (15 ml, three times a day) in a prospective, double-blind randomized trial as prophylaxis against cytotoxic therapy-induced damage to oral soft tissues. Seventy subjects, forty inpatients receiving high-dose chemotherapy and thirty outpatients receiving high-dose head and neck radiation therapy, were evaluated. Chlorhexidine mouthrinse significantly reduced the incidence of oral mucositis in the chemotherapy group on day 14 (p less than 0.02) and at 1 week follow-up on day 28 (p less than 0.002). Mucositis in the patients undergoing chemotherapy who received chlorhexidine also resolved more rapidly. Mucositis severity was significantly less compared to the control chemotherapy group on day 14 (p less than 0.03), day 21 (p less than 0.04), and on 1 week follow-up (p less than 0.02). Concomitant trends in the reduction in oral streptococci and yeast were noted in the chemotherapy group receiving chlorhexidine mouthrinse. Although no differences were observed in oral mucositis between the control and chlorhexidine groups of patients undergoing high-dose radiotherapy, similar reductions of oral microflora to those seen in the chemotherapy population were also noted for patients undergoing radiation therapy who received chlorhexidine. Although generally not significant, some increase in gram-negative bacilli was noted in the chlorhexidine-treated patients in both the chemotherapy and radiotherapy groups, but there was no correlation with increased systemic infection. Prophylactic chlorhexidine mouthrinse reduces oral mucositis and microbial burden in patients with cancer undergoing intensive chemotherapy.

Adult↗

The antimicrobial activity in vitro of chlorhexidine, a mixture of isothiazolinones ('Kathon' CG) and cetyl trimethyl ammonium bromide (CTAB).

Chlorehexidine, two 4% chlorhexidine antiseptic handwashes ('Bioprep' and 'Hibiclens'), cetyl trimethyl ammonium bromide (CTAB) and isothiazolinones ('Kathon') were tested against Staphylococcus aureus, Micrococcus luteus, Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, Proteus vulgaris and Candida albicans. The activities measured were the minimum inhibitory concentration (MIC), minimum microbicidal concentration (MMC), rate of kill in water and broth, effect of organic soil, the development of microbial resistance on continuous exposure and agent bioavailability in media and formulation. 'Kathon' was the most active microbistatic agent showing maximal activity at low concentration, least inactivation by organic soil and media components and the lowest level of development of bacterial resistance. It was synergistic with chlorhexidine against S. marcescens and P. aeruginosa. Media, formulation components and organic soil affected the performance of chlorhexidine and CTAB. Chlorhexidine was more broadly active than CTAB but showed a greater reduction in activity in the presence of soil and engendered a greater level of bacterial resistance. It was more rapidly bactericidal to P. aeruginosa and S. marcescens than to S. aureus. Stable resistance to chlorhexidine and CTAB was developed by P. aeruginosa and S. marcescens, the latter showing the higher level of resistance. Chlorhexidine-resistant strains were also resistant to CTAB. The antiseptic formulations were more rapidly bactericidal than chlorhexidine alone but were otherwise of comparable activity. Mixtures of disinfectants, in particular a combination of chlorhexidine and a preservative level of 'Kathon', were more active than single disinfectants. The importance of standardization of media and test conditions and the use of chemically defined media for accurate and reproducible in-vitro testing of disinfectant activity is emphasized. Disinfection kinetics, expressed as time-kill curves, log reduction factors or decimal reduction times were shown to be valuable in differentiating microbistatic from microbicidal activity, showing the effects of dilution and soil on activity and indicating possible different mechanisms of action.

Anti-Infective Agents, Local↗

"Clinical efficacy and expression of antimicrobial resistance genes after using a novel herbal mouthwash compared to chlorhexidine: A Randomised controlled trial in generalised gingivitis patients".

OBJECTIVES: Chlorhexidine, the gold-standard mouthwash, has several disadvantages, like promotion of antimicrobial resistance. Herbal mouthwashes are emerging as alternatives to chlorhexidine. However, its impact on antimicrobial resistance remains unclear. The aim of the study was to compare the clinical efficacy and the expression of antimicrobial resistance genes of chlorhexidine with a novel herbal mouthwash. DESIGN: Sixty patients with generalised gingivitis were randomly assigned to two groups using block randomisation. After professional mechanical plaque removal patients were instructed to use either chlorhexidine or a novel herbal mouthwash (patented composition) for two weeks. Tetracycline resistance (tetM) and macrolide efflux (mefI) gene expression in subgingival plaque were analysed using real-time polymerase chain reaction. Intragroup comparisons were performed with a paired t-test and Wilcoxon signed-rank test for parametric and nonparametric data. Intergroup comparisons employed unpaired t-test, chi-square test, and Mann-Whitney test. RESULTS: A significant reduction in bleeding, plaque, pocket depth and and patient reported outcomes were noticed in both groups. But reduction in plaque was more significant in chlorhexidine group. tetM and mefI genes significantly upregulated in the chlorhexidine group, while it was downregulated with herbal mouthwash (fold change 1.79 ± 0.74 and 0.60 ± 0.43 for tetM, and 1.83 ± 0.87 and 0.51 ± 0.44 for mefI). However, patients' perception of taste, freshness, and overall satisfaction was better in the chlorhexidine group. CONCLUSIONS: The increased expression of antimicrobial resistance genes following chlorhexidine use warrants careful consideration. Herbal mouthwash is an effective, safer alternative with comparable clinical benefits and less impact on antimicrobial resistance.

Humans↗

Chlorhexidine vaginal irrigation for the prevention of peripartal infection: a placebo-controlled randomized clinical trial.

OBJECTIVE: Our purpose was to determine whether chlorhexidine vaginal irrigation prevents maternal peripartal infection. STUDY DESIGN: A double-blinded, placebo-controlled, randomized trial was performed. Single 200 ml irrigations of either 0.2% chlorhexidine solution or sterile water placebo were given in active labor or before planned cesarean delivery. The primary outcome measure was the combined rate of chorioamnionitis and endometritis (which were mutually exclusive diagnoses). RESULTS: A total of 1024 patients were enrolled: 508 in the chlorhexidine group and 516 in the placebo group. The two groups were generally well balanced on important clinical factors but differed (p < 0.05) in rates of nulliparity (chlorhexidine 42%, placebo 52%), intrauterine pressure catheter usage (chlorhexidine 65%, placebo 72%), and presence of meconium (chlorhexidine 17%, placebo 22%). There were no recognized adverse maternal or neonatal reactions to irrigation. Rates of infection (chorioamnionitis + endometritis) did not differ significantly between the groups, chlorhexidine 10% versus placebo 13% (relative risk 0.8, 95% confidence interval 0.5 to 1.1). Stratified and logistic regression analyses supported the primary univariate analysis. Neonatal outcomes, including sepsis rates of 0.4%, were equivalent for the groups. CONCLUSION: As used in this trial, chlorhexidine lacked efficacy in the prevention of maternal peripartal infection.

Adult↗

Effects of chlorhexidine on human taste perception.

Chlorhexidine, a bis-cationic biguanide antiseptic, greatly reduces the perceived intensity of the salty prototype sodium chloride and may prove to be an important probe of mechanisms that underlie the human salty taste quality. Chlorhexidine, which tastes bitter, also reduces quinine hydrochloride taste intensity, but neither sweet sucrose nor sour citric acid is affected. Perceptual intensity rating and quality identification were measured for human subjects before and for 30 min following treatment with 1.34 mM chlorhexidine gluconate. In one experiment, test stimuli were the taste-quality prototypes; in a second experiment, stimuli were series of sodium, halide and sulfate salts. Experiment 1 showed a single 3-min chlorhexidine treatment resulted in reductions in taste intensity that persisted for at least 30 min. Experiment 2 showed a single 2-min chlorhexidine treatment reduced perceptual intensities of halide and sulfate salts except those with divalent cations. Chlorhexidine impaired identification of the salty quality and produced a bitter quality in nonbitter salts and impaired identification of the bitter quality of quinine, but not bitter salts. The specific effect of chlorhexidine on the bitterness of quinine suggests it may bind to the same receptor as quinine. The ability of chlorhexidine to specifically disrupt saltiness of a wide range of salts is consistent with proposed peripheral transduction mechanisms for the salty quality that involve transepithelial ion transport.

Adolescent↗

Side-effects and patient acceptance of 0.2% versus 0.1% chlorhexidine used as post-operative prophylactic mouthwash.

In a double-blind parallel group study including 30 patients, the side-effects and patient acceptance of chlorhexidine mouthwash 0.2% and 0.1% were studied. Side-effects such as loss of taste, burning sensation of the oral mucosa, subjective dryness of the oral cavity and discoloration of teeth and tongue were encountered. There was no statistically significant difference between the chlorhexidine groups with respect to the frequency of the reported side-effects. However, the taste of chlorhexidine 0.1% was significantly better accepted than chlorhexidine 0.2%. 4 patients discontinued the use of chlorhexidine 0.2% before the end of the trial. The quality of the experienced side-effects was stated by the patients as the reason for the discontinuation of chlorhexidine 0.2%. The present work concludes with the recommendation of chlorhexidine 0.1% compared to chlorhexidine 0.2% as a prophylactic mouthwash after oral surgical interventions.

Adult↗

Vaginal disinfection with chlorhexidine during childbirth.

The purpose of this study was to determine whether chlorhexidine vaginal douching, applied by a squeeze bottle intra partum, reduced mother-to-child transmission of vaginal microorganisms including Streptococcus agalactiae (streptococcus serogroup B = GBS) and hence infectious morbidity in both mother and child. A prospective controlled study was conducted on pairs of mothers and their offspring. During the first 4 months (reference phase), the vaginal flora of women in labour was recorded and the newborns monitored. During the next 5 months (intervention phase), a trial of randomized, blinded placebo controlled douching with either 0.2% chlorhexidine or sterile saline was performed on 1130 women in vaginal labour. During childbirth, bacteria were isolated from 78% of the women. Vertical transmission of microbes occurred in 43% of the reference deliveries. In the double blind study, vaginal douching with chlorhexidine significantly reduced the vertical transmission rate from 35% (saline) to 18% (chlorhexidine), (P < 0.000 1, 95% confidence interval 0.12-0.22). The lower rate of bacteria isolated from the latter group was accompanied by a significantly reduced early infectious morbidity in the neonates (P < 0.05, 95% confidence interval 0.00-0.06). This finding was particularly pronounced in Str. agalactiae infections (P < 0.0 1). In the early postpartum period, fever in the mothers was significantly lower in the patients offered vaginal disinfection, a reduction from 7.2% in those douched using saline compared with 3.3% in those disinfected using chlorhexidine (P < 0.05, 95% confidence interval 0.01-0.06). A parallel lower occurrence of urinary tract infections was also observed, 6.2% in the saline group as compared with 3.4% in the chlorhexidine group (P < 0.01, 95% confidence p interval 0.00-0.05). This prospective controlled trial demonstrated that vaginal douching with 0.2% chlorhexidine during labour can significantly reduce both maternal and early neonatal infectious morbidity. The squeeze bottle procedure was simple, quick, and well tolerated. The beneficial effect may be ascribed both to mechanical cleansing by liquid flow and to the disinfective action of chlorhexidine.

Adult↗

Use of chlorhexidine-impregnated dressing to prevent vascular and epidural catheter colonization and infection: a meta-analysis.

OBJECTIVES: Vascular and epidural catheter-related infections cause significant morbidities and mortality in hospitalized patients. This meta-analysis assessed the effect of chlorhexidine-impregnated dressing on the risk of vascular and epidural catheter bacterial colonization and infection. METHODS: Literature search was based on MEDLINE (1966 to 1 November 2005), EMBASE and Cochrane Controlled Trials Register (2005 issue 3) databases. Only randomized controlled clinical trials comparing chlorhexidine-impregnated dressing with placebo or povidine-iodine dressing were included in this meta-analysis. Two reviewers reviewed and extracted the data independently. RESULTS: Eight studies assessing a single type of chlorhexidine-impregnated dressing were identified and subjected to meta-analysis. The chlorhexidine-impregnated dressing reduced the risk of epidural [3.6% versus 35%, odds ratio (OR) 0.07, 95% CI: 0.02-0.31, P=0.0005] and intravascular catheter or exit-site bacterial colonization (14.8% versus 26.9%, OR 0.47, 95% CI: 0.34-0.65, P<0.00001) (overall 14.3% versus 27.2%, OR 0.40, 95% CI: 0.26-0.61; P<0.0001). The use of chlorhexidine-impregnated dressing was associated with a trend towards reduction in catheter-related bloodstream or CNS infections (2.2% versus 3.8%, OR 0.58, 95% CI: 0.29-1.14, P=0.11). Local cutaneous reactions to chlorhexidine-impregnated dressing were reported in 5.6% of the patients in three studies (OR 8.17, 95% CI: 1.19-56.14, P=0.04), and 96% of these reactions occurred in neonatal patients. The number needed to prevent one episode of intravascular catheter-related bloodstream infection was 142 for an average period of catheter in situ of 10 days and a change of dressing every 5 days. The cost of preventing one vascular catheter-related bloodstream infection was estimated to be pound298 (US$532.5). CONCLUSIONS: Chlorhexidine-impregnated dressing is effective in reducing vascular and epidural catheter bacterial colonization and is also associated with a trend towards reduction in catheter-related bloodstream or CNS infections. A large randomized controlled trial is needed to confirm whether chlorhexidine-impregnated dressing is cost-effective in preventing bacterial infection related to vascular and epidural catheters.

Anti-Infective Agents, Local↗

Topical chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis.

OBJECTIVE: To assess the efficacy of topical chlorhexidine for prevention of ventilator-associated pneumonia (VAP) in a meta-analysis. DATA SOURCE: Computerized PubMed and MEDLINE search supplemented by manual searches for relevant articles. STUDY SELECTION: Randomized controlled trials evaluating efficacy of topical chlorhexidine applied to the oropharynx vs. placebo or standard care for prevention of VAP. DATA EXTRACTION: Data were extracted on patient population, inclusion and exclusion criteria, diagnostic criteria for VAP, form and concentration of topical chlorhexidine used, incidence of VAP, and overall mortality. DATA SYNTHESIS: Data on incidence of VAP and mortality were abstracted as dichotomous variables. Pooled estimates of the relative risk and 95% confidence intervals were obtained using the DerSimonian and Laird random effects model and the Mantel-Haenszel fixed effects model. Heterogeneity was assessed using the Cochran Q statistic and I. Subgroup analyses were used to explore heterogeneity. RESULTS: Seven randomized controlled trials met the inclusion criteria. Topical chlorhexidine resulted in a reduced incidence of VAP (relative risk, 0.74; 95% confidence interval, 0.56-0.96; p=.02) using a fixed effects model. Using the more conservative random effects model, the point estimate was similar (relative risk, 0.70; 95% confidence interval, 0.47-1.04; p=.07), but the results failed to achieve statistical significance. The I test showed moderate heterogeneity. Subgroup analysis showed that the benefit of chlorhexidine was most marked in cardiac surgery patients (relative risk, 0.41; 95% confidence interval, 0.17-0.98; p=.04). There was no mortality benefit with chlorhexidine although the sample size was small. CONCLUSIONS: Our analysis showed that topical chlorhexidine is beneficial in preventing VAP; the benefit is most marked in cardiac surgery patients. A large randomized trial is needed to determine the impact of topical chlorhexidine on mortality.

Administration, Topical↗

Influence of chlorhexidine rinsing on the healing of oral mucosa and osseous lesions.

The influence of chlorhexidine rinsing on wound healing was studied using standardized, open mucosal-osseous wounds in the left side of the palate in Wistar rats. In five test groups, each containing 10 rats, rinsing was performed twice daily for 30 sec with 0.1, 0.2 and 0.5% chlorhexidine solution, chlorhexidine solution vehicle, and Ringer solution. A sixth test group (control) was not rinsed at all. Seven days postoperatively, wound healing was evaluated clinically (size of the defect) and histomorphometrically (percent composition of mature connective tissue, immature connective tissue, granulation tissue, fibrin with granulocytic infiltrate). Clinically it was clear that wound healing was best in those animals that rinsed with Ringer solution, and worst in those that rinsed with 0.5% chlorhexidine solution. Increasing concentration of chlorhexidine caused a delay in wound healing, which in the following cases resulted in significant differences: rinsing with Ringer solution and vehicle versus all concentrations of chlorhexidine, no rinsing versus 0.5% chlorhexidine. Intensive rinsing with high concentrations of chlorhexidine may, after oral surgical operations, especially surgery in which bone is exposed, result in delay and disturbance of wound healing in humans.

Animals↗

The effects of a 0.2% chlorhexidine gluconate mouthrinse on plaque, toothstaining and candida in aphthous ulcer patients. A double-blind placebo-controlled cross-over study.

Despite the known effectiveness of 0.2% chlorhexidine gluconate mouthwash in preventing plaque formation, relatively few studies have assessed adjunctive benefit to normal unsupervised oral hygiene measures. Furthermore, there have been few accurate measurements of toothstaining in the presence of normal oral hygiene and little data of effects on oral candidal carriage. This study was a double-blind placebo-controlled cross-over study of a 0.2% chlorhexidine gluconate mouthwash used 3 times daily on plaque, staining and candidal carriage in a group of recurrent aphthous ulcer suffers who maintained normal oral hygiene measures. At the end of 2 6-week treatment periods, baseline plaque scores were reduced by active and placebo mouthwashes. Chlorhexidine significantly reduced plaque compared to the placebo. Staining has markedly and significantly increased during chlorhexidine rinsing. Candidal carriage was present in 22.2% of this group and there was no significant effect of chlorhexidine on the mean number of candidal colonies. The distribution of plaque and staining by tooth was plotted and observationally studied. Baseline and placebo treatment plaque distributions indicated the considerable relevance of toothbrushing behaviour for plaque distribution. The effects of toothbrushing on plaque distribution were minimised during the use of chlorhexidine. Staining associated with chlorhexidine showed a distribution again suggesting the influence of toothbrushing. In conclusion, chlorhexidine has significant adjunctive effects on plaque inhibition in the presence of normal unsupervised oral hygiene, but toothbrushing did not prevent toothstaining.

Adolescent↗

Interactions of chlorhexidine with salivary films adsorbed at solid/liquid and air/liquid interfaces.

Chlorhexidine is a cationic compound which has been shown to bind to salivary proteins and enamel through electrostatic interactions. The aims of this study were to investigate the interaction of chlorhexidine molecules with salivary films adsorbed on solid surfaces with varying physico-chemical characteristics and to investigate the effect of different concentrations of chlorhexidine on the surface tension of saliva. The interactions between 0.2% chlorhexidine digluconate with films adsorbed from whole saliva were monitored by a Rudolph Thin-film ellipsometer equipped with a He-Ne laser (632.8 nm). The films were adsorbed on hydrophilic silica surfaces which were plasma cleaned or on methylated hydrophobic surfaces. Experiments of chlorhexidine adsorption on bare surfaces were also performed. The surface tension of mixtures of whole saliva with various concentrations of (0.1%, 0.2%, 1%) chlorhexidine was monitored with a tensiometer. The results show that chlorhexidine adsorbs on both types of studied substrates. Addition of the substance followed by rinsing caused a partial desorption of the adsorbed pellicles. Furthermore, at all studied concentrations chlorhexidine reduced the interfacial tension. There are indications that the amphiphilic characteristics of the molecule play an important role in the retention of the substance in the oral cavity.

Adsorption↗

Plaque formation and gingivitis after supervised mouthrinsing with 0.2% delmopinol hydrochloride, 0.2% chlorhexidine digluconate and placebo for 6 months.

OBJECTIVES AND METHODS: A double-blind, randomized, 6-month clinical trial with parallel group design in 162 patients with gingivitis divided into three rinsing groups was conducted in order to study the efficacy and safety of a flavoured solution of delmopinol hydrochloride 2 mg ml-1 (0.2% w/v, Decapinol Mouthwash) used for supervised mouthrinsing in one rinsing group, in comparison with chlorhexidine digluconate 2 mg ml-1 (0.2% w/v, Hibitane Dental) in a second rinsing group, and placebo in the third group. The criteria of the Plaque Index (PI) were used to assess plaque formation. Bleeding on probing (BOP) to the bottom of the pocket with a standard pressure was used as the primary gingivitis assessment. The occurrence of supragingival dental calculus and extrinsic tooth staining were also assessed. In addition, patients were asked to report adverse events at each visit. RESULTS: Delmopinol and chlorhexidine exhibited lower scores of the mean PI and the BOP percentage than placebo, both at the 3-month and 6-month examinations. Furthermore, both active solutions showed a higher extent of staining of the teeth than placebo during these two observation periods. Rinsing with chlorhexidine resulted in more dental calculus than placebo after 6 months. Chlorhexidine showed lower scores for plaque formation and gingivitis development but higher scores of supragingival dental calculus (after 6 months) and tooth staining than did delmopinol. Both active solutions were reported by the patients--approximately to the same extent but more frequently than placebo--to induce taste alterations and a transient anaesthetic sensation of the oral mucosa. However, subjective staining of the teeth and tongue was reported by 16% of the delmopinol patients, but by 86% of the patients rinsing with chlorhexidine for 6 months. Furthermore, 24% of the patients in the chlorhexidine group, 9% in the delmopinol group and 4% in the placebo group wished to withdraw from treatment. CONCLUSIONS: The results from this clinical trial indicate that supervised rinsing with 0.2% delmopinol hydrochloride or with 0.2% chlorhexidine digluconate twice daily for 60 s as a supplement to normal mechanical oral hygiene procedures resulted in less plaque formation and gingivitis than rinsing with placebo. Although chlorhexidine was more effective than delmopinol regarding plaque formation and gingivitis, it was considered by the patients as less tolerable.

Adult↗

Antimicrobial activity of garlic, tea tree oil, and chlorhexidine against oral microorganisms.

OBJECTIVE: To compare the antimicrobial activity of tea tree oil, garlic, and chlorhexidine solutions against oral microorganisms. METHOD: The five-week study consisted of thirty subjects. The first week was considered baseline. All subjects used a control solution (second week), and were randomly divided into the three groups (third week): G1-0.12% chlorhexidine; G2 - 2.5% garlic (Allium sativum, L.); and G3 - 0.2% tea tree oil (Melaleuca alternifolia). Dishes containing blood agar and Mitis Salivarius Bacitracin agar (MSB) were inoculated with the subjects' saliva (collected twice a week). Total microorganisms and mutans streptococci were counted in blood agar and MSB, respectively. RESULTS: Chlorhexidine and garlic groups showed antimicrobial activity against mutans streptococci, but not against other oral microorganisms. The tea tree oil group showed antimicrobial activity against mutans streptococci and other oral microorganisms. Maintenance of reduced levels of microorganisms was observed only for garlic and tea tree oil during the two consecutive weeks (fourth and fifth). Unpleasant taste (chlorhexidine 40%, tea tree oil 30%, garlic 100%), burning sensation (chlorhexidine 40%, tea tree oil 60%, garlic 100%), bad breath (chlorhexidine 40%, tea tree oil 20%, garlic 90%), and nausea (chlorhexidine 0%, tea tree oil 10%, garlic 30%) were reported. CONCLUSION: Garlic and tea tree oil might be an alternative to chlorhexidine.

Adolescent↗

Experimental evaluation of chlorhexidine gluconate for ocular antisepsis.

Chlorhexidine gluconate is a bisguanide germicide currently available with 70% isopropanol (Hibistat, Hibitane) or a detergent (Hibiclens, Hibiscrub) for preoperative skin preparation. As these solvents are toxic to the cornea, we investigated the safety and efficacy of aqueous chlorhexidine solutions for ophthalmic use. Chlorhexidine in Tris-glycine buffer was evaluated for retardation of epithelial regeneration after experimental corneal abrasion in rabbits. Irrigant concentrations of 2.0 and 4.0% chlorhexidine significantly slowed the healing rate (0.546 and 0.076 mm/h, respectively) compared with saline controls (0.938 mm/h). Irrigant concentrations of less than or equal to 1% did not statistically delay healing (P greater than 0.4). In a separate group of animals, the right conjunctivae of pigmented rabbits were inoculated with Staphylococcus epidermidis (approximately 10(7) organisms per eye) and irrigated with 40 microliters of aqueous chlorhexidine in concentrations of 0.1, 0.5, and 1.0%; the left eyes were irrigated with saline or left untreated. Quantitative conjunctival cultures were obtained, and the total number of organisms recovered per eye was calculated. All chlorhexidine-treated eyes showed significant reduction in organisms compared with either untreated or saline-irrigated control eyes (P less than 0.001). In vitro antimicrobial susceptibility testing demonstrated chlorhexidine in concentrations of 0.1 to 4% to be highly active against a variety of gram-positive and gram-negative bacterial pathogens by disk diffusion and broth diffusion assays. Topical aqueous chlorhexidine may be an alternate agent for preoperative conjunctival antisepsis.

Animals↗

Effects of highly concentrated stannous fluoride and chlorhexidine regimes on human dental plaque flora.

The aim of this study was to determine the effect of an intensive antimicrobial treatment on the number of Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus/Actinomyces naeslundii, and the total Colony-forming Units (CFU) in plaque. The dentition of human volunteers was treated in a dental office with either chlorhexidine (5%) or stannous fluoride (8%). Following the office treatment with chlorhexidine, selected volunteers rinsed daily at home for seven or 49 days with chlorhexidine solution (0.2%), while another group flossed daily at home for seven days with dental floss impregnated with chlorhexidine. On days one, seven, 21, 35, and 49 after the local applications, we took saliva samples and plaque samples from fissures, smooth surfaces, and approximal areas. Chlorhexidine and stannous fluoride suppressed S. mutans and the Actinomyces species on all surfaces and in saliva. S. mutans on tooth surfaces was suppressed for approximately seven days and returned to the baseline level at day 21. A. viscosus/naeslundii was suppressed for more than seven days on the teeth. S. sanguis and the total CFU returned to the baseline level within seven days on all surfaces and in saliva. Rinsing or flossing with chlorhexidine suppressed S. mutans during the period of time that these supplements were used. Brushing for seven days with chlorhexidine gel (1%) without a preceding intensive chlorhexidine treatment had virtually no effect on S. mutans in approximal areas and in saliva, but suppressed S. mutans in fissures and on smooth surfaces.

Actinomyces↗

Chlorhexidine effects on membrane lipid domains of human buccal epithelial cells.

The effect of chlorhexidine gluconate on the adherence of Candida albicans to human buccal epithelial cells (BEC) and drug-induced alterations in BEC membrane-lipid packing order were examined. Treatment of BEC with attached yeasts with 0.1 and 0.2% chlorhexidine resulted in significant yeast detachment after 90 and 60 min, respectively. Following pre-treatment of BEC with greater than 0.1% chlorhexidine, yeast adherence was inhibited by greater than 80%. In parallel experiments, the fluorescence anisotropy of BEC labeled with fluorescent membrane probes--diphenylhexatriene (DPH) and trimethylammonium DPH--was assessed following exposure to chlorhexidine. The fluorescence anisotropy decreased with increasing concentrations of chlorhexidine, which indicated that the drug decreased epithelial-cell membrane-lipid packing order. Chlorhexidine concentrations that altered epithelial-cell membrane-lipid packing order, particularly in superficial regions, were similar to those drug concentrations required for detachment of adherent yeasts. Similar results were obtained with a second antifungal, nystatin A. While the effects of chlorhexidine on the buccal-cell membrane-lipid packing order were not reversed by multiple washings, the opposite situation occurred with nystatin A. The results suggest that chlorhexidine-induced alterations of BEC membrane-lipid order may be involved in the antifungal actions of the drug.

Antifungal Agents↗

Impact of umbilical cord cleansing with 4.0% chlorhexidine on time to cord separation among newborns in southern Nepal: a cluster-randomized, community-based trial.

OBJECTIVE: Within a community-based, cluster-randomized study of the effects of 4.0% chlorhexidine on omphalitis and mortality risk, we aimed to describe the distribution of times to separation and the impact of topical chlorhexidine treatment on cord-separation times. METHODS: Between November 2002 and March 2005, 15123 infants were assigned randomly within communities in southern Nepal to receive 1 of the following 3 cord-care regimens: cleansing with 4.0% chlorhexidine, cleansing with soap and water, or dry cord care. In intervention clusters, field workers cleansed the cord in the home on days 1, 2, 3, 4, 6, 8, and 10 after birth. Newborns were monitored throughout the newborn period for signs of omphalitis, and the time to cord separation was noted. Separation times were compared across treatment groups. Cord infection risk and a range of infant and household characteristics were assessed for their relationships to separation time. RESULTS: The mean separation time was shorter in dry cord care (4.24 days) and soap/water (4.25 days) clusters than in chlorhexidine clusters (5.32 days; mean difference: 1.08 days). Cords of infants who received chlorhexidine were 3.6 times more likely to separate after 7 days. Separation time was not associated with omphalitis. Home-delivered topical antiseptics, facility-based birth, and birth attendant hand-washing were associated with greater likelihoods of cord separation after 7 days of age. CONCLUSIONS: In this setting, the umbilical cord separated more rapidly than observed in hospital-based studies, and the impact of chlorhexidine cleansing on separation times was negligible. Increased cord-separation time attributable to topical chlorhexidine treatment should not be considered a factor in decision-making in settings where the baseline risk of omphalitis is high and chlorhexidine might reduce infection and mortality risks significantly.

Chlorhexidine↗