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Effect of chlorhexidine-containing detergent, non-medicated soap or isopropanol and the influence of neutralizer on bacterial pathogenicity.

In handwashing experiments with Salmonella typhimurium the effect of chlorhexidine (CHX) on the pathogenicity of surviving bacteria was assessed with and without a neutralizer in a mouse model of infection. Without neutralizer the LD50 of CHX handwash fluids was raised. Neutralizer in suspensions of untreated bacteria caused a reduction of LD50 up to 1.2 logs. Thus, in contrast to soap or alcohol, CHX without neutralizer exerted a slight 'depathogenizing' action and neutralizer a slight 'pathogenizing' effect in the experimental model used. However, in comparison to the efficiency of handwashing procedures which reduce the number of bacteria available for transfer by at least 3.0 to 4.2 logs, the size of these effects seems to be negligibly small and unpredictable. Therefore, the single most important parameter in assessing the potency of disinfectants remains the reduction of viable counts with time.

1-Propanol↗

A comparison of two bactericidal handwashing agents containing chlorhexidine.

The skin disinfectant properties of two handwashing agents containing chlorhexidine, 'Uniscrub' and 'Hibiscrub', have been compared. The two products were assessed according to their ability to remove both transient organisms and natural or resident bacteria from the skin. They were found to be equally effective as antibacterial hand disinfection agents.

Bacteria↗

A multi-centre evaluation of two chlorhexidine-containing formulations for surgical hand disinfection.

Many experimental methods have been used to assess the efficacy of products intended for surgical hand disinfection. In this study, a modification of the Peterson glove juice method was used to compare two chlorhexidine-based surgical hand disinfectants, 'Hibiscrub' and an experimental formulation, F.6115. The study was performed by four independent laboratories and data merged for analysis. There was found to be no significant difference between the two formulations. The results illustrate that this modified Peterson glove juice method has the potential to form the basis of a standard method for testing surgical hand disinfectants which is both relevant to the practical situation and reproducible in different laboratories.

Chlorhexidine↗

Surgical hand disinfection: effect of sequential use of two chlorhexidine preparations.

The antimicrobial efficacy of three 'two-phase' surgical hand disinfection procedures was compared, in a volunteer study, to 60% n-propanol, applied for 5 min, which is the reference hand-disinfection procedure used in Austria and West Germany (FRG). The procedures involved sequential use of unmedicated soap or a disinfectant-detergent containing 4% chlorhexidine gluconate (CHX; 'Hibiscrub') followed by a handrub preparation containing 70% w/w isopropanol plus 0.5% CHX ('Hibisol'). The immediate and sustained effects (3 h) of washing with unmedicated soap (3 min) followed by rubbing on 'Hibisol' (4 min) were significantly smaller (log10 reductions of 1.72 and 1.12) than with each of the other procedures. Use of 'Hibiscrub' (3 min) and 'Hibisol' (4 min) produced log10 reductions of 2.50 and 1.71, equalling those of the reference procedure with n-propanol (2.49 and 1.78). When 'Hibisol' was used for 5 min rather than 4 min, a considerable, though not significant, increase in effect was achieved (log10 reductions of 2.90 and 2.07). Replacement of unmedicated soap by 'Hibiscrub' could significantly improve the effectiveness of the hand disinfection procedure commonly used by surgeons in German-speaking countries; namely to wash hands first with soap and then disinfect them with an alcoholic preparation. It may also be of additional advantage as this adds another 'layer' of CHX when 'Hibisol' rather than alcohol alone is used.

1-Propanol↗

Non-toxic antiseptic irrigation with chlorhexidine in experimental revascularization in the rat.

The effect of different wound irrigation fluids upon femoral arteries and veins was investigated in the rat, using microsurgical techniques. Toxicity was evaluated by microscopical observation after selective staining of histological slides. Povidone-iodine, 10%, proved to be a very irritant solution, provoking an attack on the vascular endothelium and secondary thrombosis. Chlorhexidine at 0.05%, 0.02% and 0.001% was found by contrast to have a very low toxicity which was comparable to physiological saline. Experimental investigation of antiseptic solutions should not only include the determination of the antibacterial effect, but also the potential for cell toxicity, using an irrigation technique.

Animals↗

Handwashing in a neonatal intensive care nursery: product acceptability and effectiveness of chlorhexidine gluconate 4% and triclosan 1%.

The effectiveness of triclosan 1% w/v against methicillin-resistant Staphylococcus aureus (MRSA) and its effect on skin were compared with chlorhexidine gluconate 4% w/v ('Hibiclens') in a 7-week trial. Clinical information of MRSA rates obtained during the previous 10 months and results from earlier user acceptability trials were included. The average number of new cases of MRSA per week was reduced from 3.4 to 0.14 (P less than 0.0001) in the experimental ward whilst no significant changes occurred in the control ward. Staff reported less skin damage and a higher rate of acceptance with the experimental product. Based on results of the trial, a proposal to introduce triclosan for a 12-month study period has been accepted.

Aerosols↗

In-vitro evaluation of povidone-iodine and chlorhexidine against methicillin-resistant Staphylococcus aureus.

The in-vitro activity of povidone-iodine (PVP-I) and chlorhexidine (CHX) against 33 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) was evaluated by a quantitative suspension test method. Bactericidal potency was measured by the logarithmic reduction factors (LRFs) achieved with each strain, tested at dilutions 25-800 over exposure times 30-300 s using a challenge of approximately 10(7) colony forming units (cfu) ml-1. The mean LRFs achieved over all dilutions, times and strains were significantly higher for PVP-I than CHX. PVP-I exhibited a superior killing effect whether measured by rate of kill or final LRF achieved. This difference was highly significant as judged by analysis of variance (P less than 0.001). Full efficacy of an antiseptic has been defined as a safe LRF greater than five. Over the dilution range 25-200 this was achieved by CHX with only three of 33 strains. In contrast, PVP-I achieved full efficacy with all 33 strains.

Chlorhexidine↗

Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns.

Effective topical antimicrobial agents decrease infection and mortality in burn patients. Chlorhexidine phosphanilate (CHP), a new broad-spectrum antimicrobial agent, has been evaluated as a topical burn wound dressing in cream form, but preliminary clinical trials reported that it was painful upon application. This study compared various concentrations of CHP to determine if a tolerable concentration could be identified with retention of antimicrobial efficacy. Twenty-nine burn patients, each with two similar burns which could be separately treated, were given pairs of treatments at successive 12-h intervals over a 3-day period. One burn site was treated with each of four different CHP concentrations, from 0.25 per cent to 2 per cent, their vehicle, and 1 per cent silver sulphadiazine (AgSD) cream, an antimicrobial agent frequently used for topical treatment of burn wounds. The other site was always treated with AgSD cream. There was a direct relationship between CHP concentration and patients' ratings of pain on an analogue scale. The 0.25 per cent CHP cream was closest to AgSD in pain tolerance; however, none of the treatments differed statistically from AgSD or from each other. In addition, ease of application of CHP creams was less satisfactory than that of AgSD. It was concluded that formulations at or below 0.5 per cent CHP may prove acceptable for wound care, but the vehicle system needs pharmaceutical improvement to render it more tolerable and easier to use.

Administration, Topical↗

Comparison of silver sulphadiazine 1 per cent, silver sulphadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent and mafenide acetate 8.5 per cent for topical antibacterial effect in infected full skin thickness rat burn wounds.

Silver sulphadiazine 1 per cent (SS), silver sulphadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent (SS + CD 0.2 per cent) and mafenide acetate 8.5 per cent (MA) were compared to assess the antibacterial effect of once daily application on experimental rat 20 per cent full skin thickness burn wounds seeded 24 h earlier with 10(8) microorganisms originally isolated from infected wounds of burned patients. Separate series evaluated Staph. aureus, Enterococcus faecalis, Enterobacter cloacae and Ps. aeruginosa. The mean concentration of all four organisms recovered after 1 week from full thickness biopsies of eschar and from separate biopsies of subjacent muscle was less in MA and SS + CD 0.2 per cent treated animals compared with those treated with SS alone. The mean concentration in muscle and eschar following treatment with MA was less for wounds seeded with Staph. aureus and Ps. aeruginosa than with SS + CD 0.2 per cent treatment, while the mean concentration in eschar application of SS + CD 0.2 per cent was less than with MA for E. faecalis seeded wounds.

Administration, Topical↗

Uptake of 14C-chlorhexidine diacetate to Escherichia coli and Pseudomonas aeruginosa and its release by azolectin.

Uptake of 14C-labelled chlorhexidine diacetate (14C-CHA) by wild-type and envelope mutant strains of Escherichia coli and Pseudomonas aeruginosa was very rapid. Maximum uptake was observed within a contact time of 20 s with no additional binding on increased contact, and was concentration-dependent. In contrast to this rapid binding of 14C-CHA, bactericidal studies revealed that the lethal activity of low concentrations of unlabelled CHA was slow, although higher concentrations had a rapid effect. Comparison of a wild-type strain with its envelope mutants indicated that there was little difference in 14C-CHA uptake, in minimal inhibitory concentrations or in bactericidal activity. Azolectin was found to be an effective neutralising agent of biguanide action, but in in vitro agar tests and in reducing or removing the amount of 14C-CHA taken up by the cells.

Chlorhexidine↗

The effects of a 0.12% chlorhexidine gluconate mouthrinse on orthodontic patients aged 11 through 17 with established gingivitis.

The purpose of this study was to assess the effectiveness of a 0.12% chlorhexidine gluconate (CH) mouthrinse, Peridex, on orthodontic patients 11 through 17 years of age with established gingivitis. Thirty-four subjects were divided into two groups (CH and placebo) of 17 subjects each on the basis of gender, and they were evaluated at baseline, at 6 weeks, and at 12 weeks in a double-blinded manner. The gingival index (GI) of Löe and Silness, the plaque index (PI) of Silness and Löe, the Eastman Interproximal Bleeding Index, and the CWRU staining index were recorded for each subject. The subjects in the CH group, as compared with the placebo group, had statistically significant reductions, expressed as percent reductions against baseline, at the conclusion of this 3-month period: PI = 64.9%, GI = 60.0%, and gingival bleeding = 77.2%. Staining was in the moderate range, and it was concentrated on the mandibular lingual surfaces. Peridex, in combination with mechanical plaque removal, proved to be an important therapeutic agent in controlling gingival inflammation, bleeding, and plaque accumulation in orthodontic patients 11 through 17 years of age with established gingivitis.

Adolescent↗

In vivo effects of fluoride, chlorhexidine and zinc ions on acid formation by dental plaque and salivary mutans streptococcus counts in patients with irradiation-induced xerostomia.

Irradiation therapy including major salivary glands may result in xerostomia and enhanced susceptibility to dental caries. The present aim was to assess the ability of mouthrinses with F-, Zn2+, and chlorhexidine (CH), in various combinations, to reduce acidogenic potential of dental plaque and salivary mutans streptococcus counts (SMSC) in 7 patients with xerostomia secondary to irradiation. The patients rinsed twice daily for 3 weeks with the following test solutions: (1) 12 mmol/l NaF (F; control), (2) NaF + 20 mmol/l ZnCl2 (F-Zn), and (3) NaF + 1.1 mmol/l CH (F-CH). Resting periods (F) of varying lengths were incorporated. Acid formation by dental plaque was monitored as plaque pH response to a sucrose mouthrinse, at the end of each test period, 4 h after mouthrinsing with test solution. Plaque pH was measured repeatedly at 2-8 sites in each patient before, and up to 60 min after the sucrose mouthrinse using touch microelectrodes. SMSC were determined using Dentocult SM-Strip mutans. Compared with F, F-CH significantly (P < or = 0.02) reduced acid formation by plaque and SMSC, whereas F-Zn did not affect acid formation or SMSC significantly. Pilot experiments in 4 patients showed mouthrinses with NaF + 0.55 mmol/l CH + 10 mmol/l Zn2+ to be ineffective, whereas NaF + 2.2 mmol/l CH was highly effective, but no better than F-CH. Twice daily mouthrinses with 12 mmol/l NaF in combination with 1.1 mmol/l CH may be an effective regimen to prevent post-irradiation caries.

Adult↗

Chlorhexidine-releasing methacrylate dental composite materials.

Light curable antibacterial, dental composite restoration materials, consisting of 80 wt% of a strontium fluoroaluminosilicate glass dispersed in methacrylate monomers have been produced. The monomers contained 40-100 wt% of a 10 wt% chlorhexidine diacetate (CHXA) in hydroxyethylmethacrylate (HEMA) solution and 60-0 wt% of a 50/50 mix of urethane dimethacrylate (UDMA) and triethyleneglycol dimethacrylate (TEGDMA). On raising HEMA content, light cure polymerisation rates decreased. Conversely, water sorption induced swelling and rates of diffusion controlled CHXA release from the set materials increased. Experimental composites with 50 and 90 wt% of the CHXA in HEMA solution in the monomer were shown, within a constant depth film fermentor (CDFF), to have slower rates of biofilm growth on their surfaces between 1 and 7 days than the commercial dental composite Z250 or fluoride-releasing dental cements, Fuji II LC and Fuji IX. When an excavated bovine dentine cylinder re-filled with Z250 was placed for 10 weeks in the CDFF, both bacteria and polymers from the artificial saliva penetrated between the material and dentine. With the 50 wt% experimental HEMA/CHXA formulation, this bacterial microleakage was substantially reduced. Polymer leakage, however, still occurred. Both polymer and bacterial microleakage were prevented with a 90 wt% HEMA/CHXA restoration in the bovine dentine due to swelling compensation for polymerisation shrinkage in combination with antibacterial release.

Animals↗

Antibacterial effects and physical properties of glass-ionomer cements containing chlorhexidine for the ART approach.

OBJECTIVES: Since atraumatic restorative treatment (ART) involves removal of carious lesions with manual instruments, improvement of filling materials to guarantee greater success should be considered. This study aimed to evaluate antibacterial, physical, and bonding properties of glass-ionomer cements (GIC) containing chlorhexidine (CHX), and to determine optimal concentrations for incorporation of agents to obtain antibacterial GICs for use with the ART approach. METHODS: CHX diacetate combined with CHX dihydrochloride was added to control GIC powder to obtain concentration ratios of 1/0, 2/0, 3/0, 1/1, or 2/2% w/w. Antibacterial activity of each cement against Streptococcus mutans, Lactobacillus casei or Actinomyces naeslundii was examined using agar-diffusion methods, and release of CHX was analyzed by HPLC. Compressive strength, bond strength to dentin, and setting time were measured, and compared with those of control samples. RESULTS: All experimental GICs exhibited inhibition of three bacteria, but sizes of inhibition zones and concentrations of CHX released were not dependent upon CHX content. Incorporation of CHX diacetate at 2% or greater, significantly decreased compressive strength, and bond strength to dentin was adversely affected by addition of CHX diacetate at 2% or more (p<0.05, ANOVA, Fisher's PLSD test), although setting time was extended a little by addition of any concentrations of CHX. SIGNIFICANCE: The present results demonstrate that experimental GICs containing CHX are effective in inhibiting bacteria associated with caries, and incorporation of 1% CHX diacetate is optimal to give appropriate physical and bonding properties.

Actinomyces↗

Poly(ethylene-co-vinyl acetate) copolymer matrix for delivery of chlorhexidine and acyclovir drugs for use in the oral environment: effect of drug combination, copolymer composition and coating on the drug release rate.

OBJECTIVES: This study utilizes a bio-compatible ethylene vinyl acetate (EVA) copolymer to deliver drugs at therapeutic levels over extended periods of time. The release rate of an anti-fungal and an anti-microbial drug namely acyclovir (ACY) and chlorhexidine diacetate (CDA) from EVA was investigated individually and as a mixture. The effect of drug combination, the composition of the copolymer and the coating of the matrix with a different polymer on the rate of drug release are presented. METHOD: Polymer casting solutions were prepared by homogeneously dissolving EVA copolymer and the drugs in the ratio (40:1) in dichloromethane. The drugs ACY and CDA were used individually as well as in three different weight ratios maintaining the total drug concentration in the polymer at 2.5%. Different concentrations of vinyl acetate (VA) 28, 32 and 40% in the EVA matrix were used to study the release of either ACY or CDA alone while 40% VA was used for the release study of the individual drug as well as their mixtures. Thin square films of 3cmx3cm with a thickness of 0.7mm were cut from the dry sheet obtained by solvent evaporation. Coated films were prepared by dipping ACY and CDA drug-loaded EVA films (VA 40%) into EVA copolymer of VA 32% and then dried. All of the drug-loaded samples were extracted at 37 degrees C in 10ml distilled water that was replaced daily. The rate of individual drug release was measured by UV-spectrophotometer while the mixtures of drugs were measured by high performance liquid chromatography (HPLC). RESULTS: The release rate of ACY is higher than that of CDA both individually and in the ACY/CDA 50/50 mixture. In the other mixtures, the release of the drug is proportional to its concentration in the mixture. Total release of ACY is higher than CDA in most compositions. The effect of increasing the vinyl acetate content of the EVA matrix increased the drug release rate (p=0.02) while coating of films resulted in a decrease of the release rate of the drugs. SIGNIFICANCE: Measurements of the in vitro rate of drug release showed that there was a sustained release of drug at an almost constant concentration over extended period of time, thus providing a basis for oral treatment modality. We show that it is possible to alter the rate of drug release in the EVA matrix to a desired value by: (1) changing the composition of the EVA copolymer, (2) altering the mixtures of drugs and (3) coating the matrix with additional polymer. The use of mixtures of drugs that can enhance or decrease the rate of drug release may prove more effective in treating persistent oral infections in immunocompromised patients.

Acyclovir↗

Randomized, double-blind study on effectiveness of intra-alveolar chlorhexidine gel in reducing the incidence of alveolar osteitis in mandibular third molar surgery.

Chlorhexidine (CHX) mouthwash is a good prophylactic agent for postextraction alveolar osteitis (AO), a very common complication. Recently, a bio-adhesive gel to deliver the active substance, CHX, has been introduced. The intra-alveolar positioning of the bio-adhesive gel allows more direct and prolonged action of CHX, which could be useful in the prevention of AO following extraction of impacted third molars. Presented here is a double-blind, randomised and parallel-group study evaluating the efficacy of the bio-adhesive 0.2% CHX gel (n=53) applied once within the alveolus during third molar surgery, compared to placebo gel only (n=50), in reducing the incidence of impacted third-molar postextraction AO. A 63.33% reduction in the occurrence of AO (P=0.019) was observed in the experimental group. In the control group, the occurrence of AO was 30% compared to 11% in the experimental group. Bio-adhesive 0.2% CHX gel, applied only once within the alveolus site at the time of surgery, may reduce the incidence of AO following removal of impacted third molars.

Adolescent↗

Determination of chlorhexidine (CHD) and nonylphenolethoxylates (NPEOn) using LC-ESI-MS method and application to hemolyzed blood.

Rapid and reliable methods for identification of chlorhexidine (CHD) and nonylphenolethoxylates (NPEOn) in antiseptic and hemolyzed blood using electrospray ionization mass spectrometry (ESI-MS) were developed. Fragmental analysis provides accurate evidence for the presence of CHD in the samples. For the determination of CHD in hemolyzed blood, the method was also developed using LC-ESI-MS. Linearity of calibration curve was obtained over the concentration range of 0.1-11 microg/mL with residuals from -4.3 to 6.7%. We applied the methods to the case of suicidal injection of antiseptic and successfully detected CHD and NPEOn from hemolyzed blood. The CHD concentration was 352 microg/mL.

Adult↗

Double-blind comparative study on the care of the neonatal umbilical cord using 80% ethanol with or without chlorhexidine.

We conducted a double-blind comparative study on the effectiveness of 80% ethanol (EtOH), with or without chlorhexidine (CHD), in the prevention of neonatal umbilical colonization by Staphylococcus aureus, the most frequently isolated pathogen on the neonatal umbilicus in the early period. A total of 100 neonates born at the National Tokyo Medical Centre from March to May 2000 and nursed at a maternity ward were enrolled. Forty-eight were randomly allocated to the group for whom umbilical cord disinfection was performed using 80% EtOH containing 0.5% CHD (CHD group) and 52 to disinfection with 80% EtOH alone (EtOH group). The mothers of the neonates and the nursing staff were unaware as to which disinfectant was being used. Disinfection of the umbilicus and the surrounding area was done immediately after birth and twice daily thereafter, after bathing and in the evening, throughout the hospitalization period. Specimens for bacterial culture were taken from the umbilical cord and surrounding skin on day 4 or 5 after birth. As a disinfectant susceptibility test, we checked the minimum killing concentration (MKC) of CHD and EtOH. There was no statistically significant difference between the two groups with respect to sex, gestation period, birthweight, APGAR score or delivery method. In the CHD group, S. aureus was isolated from 25% of the patients, while it was isolated from 57.7% in the EtOH group (P<0.001). In the CHD group, 50% of the S. aureus strains were MRSA, compared with 73.3% in the EtOH group (non-significant). All the S. aureus strains were killed by the combination of both CHD and EtOH at the concentrations used. In terms of the MKC90, there was no significant difference between the CHD group and the EtOH group. For the daily care of the neonatal umbilicus, disinfection using 80% EtOH containing CHD was found to be more effective than that using 80% EtOH alone in preventing colonization by S. aureus.

Anti-Infective Agents, Local↗