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Chlorhexidine gluconate.

The aim of root canal treatment is to eliminate bacteria from the infected root canal and to prevent reinfection. Biomechanical cleaning and shaping greatly reduces the number of bacteria. Nevertheless, due to anatomical complexity of the root canal system, residues and bacteria cannot be removed completely. Therefore, various substances have been used during canal preparation to remove debris, necrotic tissue, bacteria and smear layer. The most common irrigant of choice is sodium hypochlorite (NaOCI): it is an effective antimicrobial agent and tissue solvent. However, NaOCI can be toxic. Chlorhexidine gluconate (CHX) is a broad-spectrum antimicrobial agent. As a root canal irrigant and intracanal medicament, CHX has an antibacterial efficacy comparable to that of NaOCI, and is effective against resistant bacterial strains. CHX may result in residual antimicrobial activity of the dentine surface after prolonged exposure of the root canal to CHX. CHX also has a low grade of toxicity. In this review CHX will be discussed in detail.

Animals↗

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↗

Comparison of four antiseptic products containing chlorhexidine gluconate.

The purpose of this study was to compare the antimicrobic efficacies of four formulations of chlorhexidine gluconate (CHG) for handwashing under frequent-use conditions. Fifty volunteers were assigned by block randomization to one of five products: one of two liquid detergents containing 4% CHG, a liquid detergent containing 2% CHG, a foam containing 4% CHG, and a nonantiseptic soap (control). Subjects washed their hands by a standardized technique 15 times per day for 5 days. After days 1 and 5 of handwashing, there was a significant reduction in log CFU for subjects using all four CHG-containing products compared with subjects using control soap and for subjects within each group after days 1 and 5 compared with the base-line CFU counts (all P less than 0.05). There were no significant differences between the four CHG products at any testing time. We conclude that all four formulations are satisfactory for clinical use.

Adult↗

Susceptibility of Chlamydia trachomatis to chlorhexidine gluconate gel.

To identify topical antimicrobial preparations which may be effective in preventing the transmission of sexually transmitted diseases, we examined the activity of chlorhexidine gluconate (CHG) against Chlamydia trachomatis. Chlamydial elementary bodies were incubated with dilutions of CHG gel for various times from 0 to 120 min. An aliquot of each dilution was further diluted and was inoculated onto McCoy cell monolayers in individual wells in a 96-well microtiter plate. The cultures were incubated for 48 h, and the chlamydial inclusions were stained and counted. CHG gel diluted fourfold (0.0625% CHG) killed C. trachomatis serovar D, and CHG gel diluted eightfold (0.0313% CHG) killed serovar F immediately upon exposure. CHG gel diluted 16-fold (0.0156% CHG) killed serovar D, and CHG gel diluted 32-fold (0.0078% CHG) killed serovar F after 120 min of exposure. Alteration of the pH over the range of from 4 to 8 did not significantly affect its activity. The addition of 10% whole human blood decreased the CHG gel activity at 0 min but had no significant effect after 120 min of exposure. We conclude that CHG gel may be effective topically against C. trachomatis at concentrations that can be used and under conditions that are found in the female genital tract and that further studies of its antimicrobial efficacy and toxicity in vivo are warranted.

Animals↗

Comparative study on the antimicrobial effect of 0.5% chlorhexidine gluconate and 70% isopropyl alcohol on the normal flora of hands.

A gloved-hand wash method was used to compare the antimicrobial effect of chlorhexidine gluconate alcohol emollient hand wash (HIBISTAT) with that of 70% isopropyl alcohol on the normal flora of the hands (81 subjects) under conditions designed to mimic use by surgeons. Results of the immediate postwash effects on the bacterial counts for all 3 tests days showed that chlorhexidine significantly reduced the normal flora of the hands. When compared with the base line bacterial counts, there was 85, 96, and 98% reduction with chlorhexidine treatment and 84, 93, and 90% reduction with alcohol treatment on days 1,2, and 5, respectively. The difference between chlorhexidine and alcohol treatments was not statistically significant on days 1 and 2, but was significant on day 5 (P less than 0.01). For delayed postwash bacterial counts (for persistent antimicrobial effects), the overall log means were 4.9943 and 5.4684 for chlorhexidine and alcohol treatments, respectively. The difference between the two treatments was significant (P less than 0.01). After the chlorhexidien treatment, there was no significant growth of bacteria over a period of 6 h when compared with the base line bacterial counts.

1-Propanol↗

Effects of a chlorhexidine gluconate-containing mouthwash on the vitality and antimicrobial susceptibility of in vitro oral bacterial ecosystems.

Oral bacterial microcosms, established using saliva inocula from three individuals, were maintained under a feast-famine regime within constant-depth film fermenters. Steady-state communities were exposed four times daily, postfeeding, to a chlorhexidine (CHX) gluconate-containing mouthwash (CHXM) diluted to 0.06% (wt/vol) antimicrobial content. The microcosms were characterized by heterotrophic plate counts and PCR-denaturing gradient gel electrophoresis (DGGE). CHXM caused significant decreases in both total anaerobe and total aerobe/facultative anaerobe counts (P < 0.05), together with lesser decreases in gram-negative anaerobes. The degree of streptococcal and actinomycete inhibition varied considerably among individuals. DGGE showed that CHXM exposure caused considerable decreases in microbial diversity, including marked reductions in Prevotella sp. and Selenomonas infelix. Pure-culture studies of 10 oral bacteria (eight genera) showed that Actinomyces naeslundii, Veillonella dispar, Prevotella nigrescens, and the streptococci were highly susceptible to CHX, while Lactobacillus rhamnosus, Fusobacterium nucleatum, and Neisseria subflava were the least susceptible. Determination of the MICs of triclosan, CHX, erythromycin, penicillin V, vancomycin, and metronidazole for microcosm isolates, before and after 5 days of CHXM exposure, showed that CHXM exposure altered the distribution of isolates toward those that were less susceptible to CHX (P < 0.05). Changes in susceptibility distributions for the other test agents were not statistically significant. In conclusion, population changes in plaque microcosms following repeated exposure to CHXM represented an inhibition of the most susceptible flora with a clonal expansion of less susceptible species.

Bacteria↗

6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) from slow-growing Rhizobia.

6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) (NAD+-6PGD) was detected in several slow-growing strains of rhizobia, and no activity involving NADP+ was found in the same extracts. By contrast, fast-growing strains of rhizobia had NADP+-6PGD activity; most of them also had NAD+-6PGD activity. NAD+-6PGD was partially purified from the slow-growing strain Rhizobium japonicum 5006. The reaction was shown to be an oxidative decarboxylation.

Cell-Free System↗

Genetic map position of the gluconate-6-phosphate dehydrogenase gene in Salmonella typhimurium.

Gluconate-6-phosphate dehydrogenase (GND) is genetically determined in Salmonella typhimurium by a locus (gnd) mapping between the somatic antigen (rfb) and histidine (his) operons. The enzyme is constitutive. Strains of Salmonella carrying an F' genetic element which contains the gnd(+) gene have GND activity two to three times that of the wild type. This gene dosage effect was used to determine that the GND reaction is not rate-limiting for the metabolism of glucose by the pentose shunt in S. typhimurium.

Chromosome Mapping↗

Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh.

AIM: The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis. METHODS: Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial. RESULTS: 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment. CONCLUSIONS: Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available.

Adolescent↗

Comparison of the antimicrobial efficacy of povidone-iodine, povidone-iodine-ethanol and chlorhexidine gluconate-ethanol surgical scrubs.

BACKGROUND: Scrubbing of the hands and forearms with a brush and antiseptic agents has been the standard for surgical practice. However, it has been increasingly recognized that brush scrubbing may provoke side effects and that an alcohol-based hand antiseptic used in conjunction with a scrub agent enhances the effectiveness. In this study, two types of alcohol-based agents were used after a povidone-iodine (PVP-I) scrub and compared for their effectiveness. MATERIALS AND METHODS: The study was conducted as a crossover trial with 20 volunteers. After hand rubbing with PVP-I, either PVP-I-ethanol rubbing or chlorhexidine gluconate-ethanol (CHG-ethanol) rubbing was used for surgical hand cleansing. Samples were collected by the modified glove juice method to count bacteria on hands. RESULTS: In both groups, the bacterial count was significantly reduced after handwashing (p < 0.001), and the reduction was still significant after 2 h (p < 0.001 for PVP-I-ethanol and p < 0.002 for CHG-ethanol). The log(10) reduction factor (RF) in the PVP-I-ethanol group was significantly higher than that in the CHG-ethanol group immediately after handwashing (p < 0.001) but significantly lowered after 2 h (p < 0.01) to the level similar to that of CHG-ethanol. Although RF was lower in the CHG-ethanol group immediately after and 2 h after handwashing compared to the PVP-I-ethanol group, it did not decrease with time. CONCLUSION: Brushless surgical scrubbing with PVP-I-ethanol or CHG-ethanol in conjunction with PVP-I showed antiseptic effects immediately after and 2 h after handwashing. RF immediately after handwashing was significantly higher with PVP-I-ethanol compared to CHG-ethanol, but it was similar in both groups after 2 h. These results suggest that when used in combination with a PVP-I scrub, an alcohol-based hand antiseptic containing the same active agent (PVP-I in this study) has a powerful antiseptic effect; however, when it contains different antiseptic agents (i.e. CHG in this study), it should be selected carefully based on its antiseptic property.

Administration, Topical↗

Effects of chlorhexidine gluconate douche on normal vaginal flora.

The effects of a 0.5% aqueous chlorhexidine gluconate (CHG) douche on the normal vaginal flora of twenty healthy nonpregnant volunteers were investigated. The douche was applied in a premeasured 180-ml quantity daily for 7 consecutive days. Specimens for aerobic and anaerobic culture of the vaginal flora were obtained on 3 occasions from each volunteer, once before and twice after CHG use. The culture results were analyzed qualitatively and quantitatively. A blood sample was also collected within 24 h of the last CHG application to determine serum CHG concentration. Lactobacillus spp., Gardnerella vaginalis and Staphylococcus epidermidis were the most prevalent aerobic bacteria at all phases of the study and Bacteroides spp. were the most prevalent anaerobes. The composition of the normal flora was essentially the same 30 days after the last dose as the pretreatment flora. Small amounts of CHG were detected in the serum of all but one subject. No untoward effects on the participants were observed. Candida albicans counts were slightly higher, but prevalence was not significantly increased at the end of the study.

Adult↗

In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse.

The purpose of this work was to assess the in vitro antiviral effectiveness of a mouthrinse (Peridex) containing 0.12% chlorhexidine gluconate (CH) on several viruses that are associated with the oral cavity. These included herpes simplex virus (HSV), cytomegalovirus (CMV), influenza A, parainfluenza, polio, and hepatitis B (HBV). Virucidal assays in tissue cultures were performed on all viruses except HBV. The virucidal effect on HBV was assessed by inactivation of the DNA polymerase contained within the Dane particle of HBV. The CH mouthrinse had virucidal activity against all of the viruses, except polio, in as little as 30 s. The virucidal activity increased with time. However, there were differences in the responses of these viruses to the challenge of the CH mouthrinse, probably due to subtle differences in the physical/chemical structures of the virus envelopes. Results on DNA polymerase of the HBV virus were similar to those on the other viruses, except polio, suggesting a common mechanism. With respect to this mechanism, it was proposed that CH exerted its antiviral effect on the envelopes of these viruses, and that the absence of an envelope on polio precluded effectiveness against this virus.

Animals↗

Disposition of 3-hydroxyquinidine in patients receiving initial intravenous quinidine gluconate for electrophysiology testing of ventricular tachycardia.

The formation rate constant and elimination rate constant for 3-hydroxyquinidine were determined in eight patients with ventricular tachycardia. These two parameters (mean +/- SD) were found to be 0.784 +/- 0.202 and 0.042 +/- 0.058 h-1, respectively. Coefficients of determination for the computer-generated line of best fit for serum concentration-time data were 0.986 +/- 0.008. Patients received two infusions of quinidine gluconate 5 mg/kg over 30 minutes separated by a 20-30 minute electrophysiologic testing period. Unbound and total 3-hydroxyquinidine concentrations were also determined. Among the eight patients, 3-hydroxyquinidine was 61.9 percent bound. Studies in healthy volunteers had shown 50 percent binding. Linear regression of unbound and total 3-hydroxyquinidine was described by the equation Y = 0.3814X-1.448, r = 0.813. Although half-lives of 3.5-12.4 hours had been reported in healthy volunteers, prolonged half-lives were observed in all but two of our arrhythmia patients.

Adult↗

Characterization of Sulfolobus solfataricus 2-keto-3-deoxy-D-gluconate kinase in the modified Entner-Doudoroff pathway.

The thermoacidophilic archaeon Sulfolobus solfataricus is known to utilize D-glucose via the nonphosphorylated Entner-Doudoroff (ED) pathway. But, the genome database shows that this microorganism has a gene (kdgK) encoding 2-keto-3-deoxy-D-gluconate (KDG) kinase (KDGK) which phosphorylates KDG to 2-keto-3-deoxy-6-phosphogluconate. Interestingly, kdgK and three other genes in the modified ED pathway are organized as an operon-like structure. In this study, we report confirmation of the catalytic activity of the S. solfataricus KDGK protein. We also found that the kdgK gene was transcribed as polycistronic transcripts. Proteome analysis of cell lysate revealed that all gene products in the kdgK operon were expressed as functional proteins. These results strongly indicate that S. solfataricus metabolizes D-glucose via the 'partially' nonphosphorylated ED pathway. A purified recombinant S. solfataricus KDGK had K(m) and k(cat) values of 0.14 mM and 60.8 s(-1) respectively for KDG, and showed maximal activity at temperatures between 70 and 80 degrees C and pHs between 7.0 and 8.0.

Amino Acid Sequence↗

Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery.

UNLABELLED: STUDY OFJECTIVE: The purpose of this study was to test the effectiveness of oropharyngeal decontamination on nosocomial infections in a comparatively homogeneous population of patients undergoing heart surgery. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled clinical trial. Experimental and control groups were selected for similar infection risk parameters. SEETTING: Cardiovascular ICU of a tertiary care hospital. PATIENTS: Three hundred fifty-three consecutive patients undergoing coronary artery bypass grafting, valve, or other open heart surgical procedures were randomized to an experimental (n=173) or control (n=180) group. Heart and lung transplantations were excluded. INTERVENTIONS: The experimental drug chosen was 0.12% chlorhexidine gluconate (CHX) oral rinse. MEASUREMENTS AND RESULTS: The overall nosocomial infection rate was decreased in the CHX-treated patients by 65% (24/180 vs 8/173; p<0.01). We also noted a 69% reduction in the incidence of total respiratory tract infections in the CHX-treated group (17/180 vs 5/173; p<0.05). Gram-negative organisms were involved in significantly less (p<0.05) of the nosocomial infections and total respiratory tract infections by 59% and 67%, respectively. No change in bacterial antibiotic resistance patterns in either group was observed. The use of nonprophylactic IV antibiotics was lowered by 43% (42/180 vs 23/173; p<0.05). A reduction in mortality in the CHX-treated group was also noted (1.16% vs 5.56%). CONCLUSIONS: Inexpensive and easily applied oropharyngeal decontamination with CHX oral rinse reduces the total nosocomial respiratory infection rate and the use of nonprophylactic systemic antibiotics in patients undergoing heart surgery. This results in significant cost savings for those patients who avoid additional antibiotic treatment.

Anti-Bacterial Agents↗

Stabilized ferrous gluconate as iron source for food fortification: bioavailability and toxicity studies in rats.

The iron bioavailability and acute oral toxicity in rats of a ferrous gluconate compound stabilized with glycine (SFG), designed for food fortification, was studied in this work by means of the prophylactic method and the Wilcoxon method, respectively. For the former studies, SFG was homogeneously added to a basal diet of low iron content, reaching a final iron concentration of 20.1 +/- 2.4 mg Fe/kg diet. A reference standard diet using ferrous sulfate as an iron-fortifying source (19.0 +/- 2.1 mg Fe/kg diet) and a control diet without iron additions (9.3 +/- 1.4 mg Fe/kg diet) were prepared in the laboratory in a similar way. These diets were administered to three different groups of weaning rats during 23 d as the only type of solid nourishment. The iron bioavailability of SFG was calculated as the relationship between the mass of iron incorporated into hemoglobin during the treatment and the total iron intake per animal. This parameter resulted in 36.6 +/- 6.2% for SFG, whereas a value of 35.4 +/- 8.0% was obtained for ferrous sulfate. The acute toxicological studies were performed in two groups of 70 female and 70 male Sprague-Dawley rats that were administered increasing doses of iron from SFG. The LD50 values of 1775 and 1831 mg SFG/kg body wt were obtained for female and male rats, respectively, evidencing that SFG can be considered as a safe compound from a toxicological point of view.

Animals↗

Reducing bacterial aerosol contamination with a chlorhexidine gluconate pre-rinse.

The authors compared the effects of chlorhexidine gluconate, an antiseptic mouthwash with essential oils and water on the bacterial aerosol contamination generated by an air polishing device. Patients rinsed with one of the three solutions before treatment. Bacterial counts collected during the treatment indicate that the chlorhexidine pretreatment rinse was significantly more effective than the other solutions in reducing bacterial aerosols.

Adult↗