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Inhibition of orally produced volatile sulfur compounds by zinc, chlorhexidine or cetylpyridinium chloride--effect of concentration.

Zinc ions, chlorhexidine (CHX) and cetylpyridinium chloride (CPC) are all known to inhibit production of volatile sulfur compounds (VSCs). The objective was to examine the anti-VSC dose-response effects of each of the above agents. Oral malodor was induced in 13 test subjects using the cysteine challenge method. The oral VSC response to rinses with 6 mm l-cysteine (pH 7.2) before and 1, 2 and 3 h after rinsing with zinc ions (Zn2+: 0.1, 0.3 and 1.0%), CHX and CPC (0.025 and 0.2%) was measured. Mouth air was analysed for VSC by gas chromatography (GC) according to current methodology. Zinc had a marked dose- and time-dependent anti-VSC effect. Zinc at 1% concentration had a somewhat unpleasant taste, whereas the lowest concentration was found acceptable. Chlorhexidine maintained a moderate anti-VSC effect over time. At 3 h, 0.2% CHX was the most effective agent but tasted relatively unpleasant. Cetylpyridinium at a concentration of 0.2% was only marginally more effective than 0.025% CHX over the 3 h, while 0.025% CPC had no better anti-VSC effect than water at both 2 h and 3 h. It was concluded that the three test agents demonstrated different anti-VSC kinetics. Although Zn had the best anti-VSC effect at 1 h, 0.2% CHX was at least as effective as 1% Zn at 3 h, most likely as a result of its unique substantivity.

Adult↗

Comparison of in-vivo antibacterial activity of two skin disinfection procedures for insertion of peripheral catheters: povidone iodine versus chlorhexidine.

Skin disinfection is a key step in the prevention of nosocomial infections especially prior to invasive procedures such as the insertion of peripheral catheters. Alcohol-based antiseptics improve bactericidal activity and decrease the time needed for skin disinfection in emergencies. A randomized study was performed in two groups of 22 volunteers to compare the in vivo bactericidal effect of two rapid disinfection procedures using povidone iodine (PVP-I) in scrub formulation followed by alcoholic PVP-I, or chlorhexidine in scrub formulation followed by alcoholic chlorhexidine. Bacteria were recovered using the cylinder scrub method. Comparison of reductions in the aerobic and anaerobic flora from baseline levels to each of the three sampling times (30 sec, 3 min, 2 h) showed no significant difference between the two procedures Log(10)reduction after 30 seconds was around 1.5 for the aerobic flora and 1.1 for the anaerobic flora. After 3 minutes the corresponding values were 2.1 and 1.8, and after 2 hours 2.0 and 1.3. The products were well tolerated in both groups. The two procedures had comparable rapid bactericidal activity in vivo.

Adult↗

Intravenous chlorhexidine gluconate causing acute respiratory distress syndrome.

CASE REPORT: A 67-year-old man undergoing a colectomy for colon cancer was unintentionally administered 0.8 mg of chlorhexidine gluconate intravenously and subsequently developed acute respiratory distress syndrome. The operation was discontinued immediately. Respiratory failure progressed despite three cycles of plasma exchange beginning on day 1. Extracorporeal membrane oxygenation for 72 h beginning on day 3 was associated with dramatic improvement. The patient showed complete recovery of intellectual function and subsequently underwent a colectomy with lymph node dissection for colon cancer. CONCLUSION: For acute respiratory distress syndrome secondary to chlorhexidine gluconate intoxication, consideration should be given to the treatment of initial respiratory distress and subsequent pneumonia. The benefit of extracorporeal membrane oxygenation and plasma exchange may merit further investigation.

Aged↗

Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus colonization.

BACKGROUND: Eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage may reduce the risk of MRSA infection and prevent transmission of the organism to other patients. METHODS: To determine the efficacy of decolonization therapy, patients colonized with MRSA were randomized (3:1 allocation) to receive treatment (2% chlorhexidine gluconate washes and 2% mupirocin ointment intranasally, with oral rifampin and doxycycline for 7 days), or no treatment. Follow-up samples for MRSA culture were obtained from the nares, perineum, skin lesions, and catheter exit sites monthly for up to 8 months. The primary outcome measure was detection of MRSA at 3 months of follow-up. Univariate and multivariable analyses were performed to identify variables associated with treatment failure. RESULTS: Of 146 patients enrolled in the study, 112 patients (87 treated; 25 not treated) were followed up for at least 3 months. At 3 months of follow-up, 64 (74%) of those treated had culture results negative for MRSA, compared with 8 (32%) of those not treated (P=.0001). This difference remained significant at 8 months of follow-up, at which time, 54% of those treated had culture results negative for MRSA (chi2=64.4; P<.0001, by log-rank test). The results of the multivariable analysis indicated that having a mupirocin-resistant isolate at baseline was associated with treatment failure (relative risk, 9.4; 95% confidence interval, 2.8-31.9; P=.0003), whereas decolonization therapy was protective (relative risk, 0.1; 95% confidence interval, 0.04-0.4; P=.0002). Mupirocin resistance emerged in only 5% of follow-up isolates. CONCLUSIONS: Treatment with topical mupirocin, chlorhexidine gluconate washes, oral rifampin, and doxycycline for 7 days was safe and effective in eradicating MRSA colonization in hospitalized patients for at least 3 months.

Administration, Intranasal↗

The effects of surfactant systems and moisturizing products on the residual activity of a chlorhexidine gluconate handwash using a pigskin substrate.

A series of handwashing experiments using a pigskin substrate and Serratia marcescens as the contaminant compared the residual activity of a chlorhexidine detergent handwash product alone and in combination with anionic and nonionic-based moisturizing products and surfactant systems. The anionic based moisturizing products and the anionic surfactant system almost completely destroyed the residual antibacterial activity of the chlorhexidine, while the nonionic-based products had minimal effect.

Administration, Topical↗

Decreased bacterial adherence and biofilm formation on chlorhexidine and silver sulfadiazine-impregnated central venous catheters implanted in swine.

OBJECTIVE: To determine if antiseptic central venous catheters impregnated with silver sulfadiazine and chlorhexidine (antiseptic) reduce bacterial adherence and biofilm formation without producing local or systemic toxicity. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Ten outbred New Hampshire pigs. INTERVENTIONS: Nonimpregnated (control) and antiseptic-impregnated catheters were inserted intravascularly into swine for 7 days. After explantation, the catheters were assessed for bacterial adherence and biofilm formation, and the surrounding tissue was assessed for signs of toxicity. Before retrieval, systemic concentrations of antimicrobials were determined. MEASUREMENTS AND MAIN RESULTS: Sequential roll plate and centrifuging were used to detect moderately and tightly adherent bacteria on the outer and luminal surfaces of the catheter. The presence of biofilm was detected by scanning electron microscopy. Tissues surrounding the catheters were examined histopathologically; systemic concentrations of chlorhexidine, sulfadiazine, and silver were determined by atomic absorption and high-performance liquid chromatography. As compared with the controls, antiseptic catheters had significantly (p < .01) fewer moderately and tightly adherent bacteria on outer and luminal surfaces, and fewer adherent bacteria when outer surfaces alone were examined (p < .01). Scanning electron microscopy showed bacterial biofilm and adherence on the control catheters but not on the antiseptic catheters. There were no abnormal histopathologic changes associated with the test catheter, and serum concentrations of the antibacterial agents were shown to be within nontoxic ranges. CONCLUSION: The antiseptic-impregnated catheters prevented bacterial adherence and biofilm formation and produced no local or systemic toxicity.

Animals↗

Comparison of 1% silver sulfadiazine with and without 1% chlorhexidine digluconate for topical antibacterial effect in the burnt infected rat.

The addition of 1% chlorhexidine digluconate to 1% silver sulfadiazine cream (CDSS) was compared with 1% silver sulfadiazine (SS) alone to assess the antibacterial effect of a once-daily application of the therapies on an experimental rat model with a 20% full-thickness burn wound seeded with 10(8) microorganisms originally isolated from infected wounds of burn patients. Separate series evaluated Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter cloacae, and Streptococcus faecalis. The mean concentration of all four organisms recovered after one week from biopsy specimens of full-thickness eschar was less in the CDSS-treated animals compared with the SS-treated animals. Microbial invasion into subjacent muscle was less frequent in animals seeded with S faecalis, while the mean concentration of bacteria recovered from muscle of animals seeded with S aureus and E cloacae was less in animals treated with CDSS compared with those treated with SS (P less than 0.05). The addition of 1% chlorhexidine digluconate to 1% silver sulfadiazine increased the antibacterial effectiveness of the latter agent.

Administration, Topical↗

Effects of chlorhexidine gluconate as an endodontic irrigant on the apical seal: short-term results.

The aim of this study was to ascertain whether chlorhexidine gluconate (0.12%), used as an endodontic irrigating solution would affect the apical seal obtained when using three different root canal cements. One hundred extracted human single-canal teeth were divided into 9 experimental groups of 10 teeth each and a positive and negative group of 5 teeth each. The teeth were decoronated at the level of the cementoenamel junction, then accessed, instrumented to a Master Apical File #50, irrigated with either sterile saline, 5.25% NaOCl or 0.12% chlorhexidine gluconate, and dried using paper points. Obturation was accomplished using lateral condensation and 1 of 3 endodontic sealers: Roth's 811, AH26, or Sealapex. At 90 and 180 days after obturation apical leakage was measured using the fluid filtration method. Using the ANOVA test the results showed no significant difference in seal related to the irrigant at both the 90- and 180-day observation periods.

Analysis of Variance↗

Effectiveness of selected materials against Enterococcus faecalis: part 3. The antibacterial effect of calcium hydroxide and chlorhexidine on Enterococcus faecalis.

It has been found that Enterococcus faecalis is most commonly isolated in failed endodontic treatment. Irrigation with chlorhexidine gluconate has been suggested based on its antimicrobial effect and substantivity. Calcium hydroxide also is an effective antimicrobial agent because of its high alkalinity. The purpose of this study was to test the individual and combined effect of calcium hydroxide and chlorhexidine against E. faecalis. The agar-diffusion test was performed on Mueller-Hinton plates. Paper disks were impregnated with: (a) CaOH powder with sterile water; (b) Pulpdent; (c) 0.12% Peridex; (d) CaOH powder with Peridex; and (e) Pulpdent with Peridex. Ampicillin served as a control. The plates were incubated at 37 degrees C for 72 h. Peridex showed significantly larger zones of inhibition compared with CaOH. No statistically significant difference was found between Peridex and the combination of CaOH and Peridex.

Analysis of Variance↗

Effect of 2% chlorhexidine gel as an intracanal medication on the apical seal of the root-canal system.

The purpose of this study was to determine what effect intracanal medications might have on the apical seal of the root-canal system. Forty-two teeth were cleaned and shaped in a crown-down manner to a size #50 K-file. The teeth were divided into three groups: (A) immediate obturation; (B) intracanal placement of calcium hydroxide placed for 14 days; and (C) 2% chlorhexidine gel placed for 14 days. After 14 days, these materials were removed using copious irrigation and obturation was completed on groups B and C. Obturation was performed using the continuous wave of condensation technique using AH Plus sealer in all groups. Leakage was evaluated 60 days after obturation by using a fluid-filtration device. Using the one-way ANOVA test, there was no statistically significant difference in leakage between the three groups. Under the conditions of this study, 2% chlorhexidine gel and calcium hydroxide paste did not adversely affect the apical seal of the root-canal system.

Analysis of Variance↗

Safety and efficacy of an improved antiseptic catheter impregnated intraluminally with chlorhexidine.

The safety and efficacy of a second-generation improved antiseptic catheter impregnated with silver sulfadiazine and increased levels of chlorhexidine on its outer surface and chlorhexidine alone on its luminal surfaces was compared in vitro and in vivo to standard antiseptic catheters impregnated with these antimicrobials on their outer surfaces only. In rat and pig intravenous models, the improved antiseptic catheter was significantly more effective in resisting both outer surface and luminal colonization compared with the standard antiseptic or control catheters. There was no evidence of tissue toxicity in any group.

Animals↗

Comparison of silver-coated dressing (Acticoat), chlorhexidine acetate 0.5% (Bactigrass), and silver sulfadiazine 1% (Silverdin) for topical antibacterial effect in Pseudomonas aeruginosa-contaminated, full-skin thickness burn wounds in rats.

Acticoat (Smith and Nephew, Istanbul, Turkey), chlorhexidine acetate 0.5%, and silver sulfadiazine 1% were compared to assess the antibacterial effect of their application on experimental burn wounds in contaminated with Pseudomonas aeruginosa in rats. All treatment modalities were effective against P. aeruginosa because there were significant differences between treatment groups and control groups. The mean eschar concentrations did not differ significantly between Acticoat and chlorhexidine acetate groups, but there were significant differences between the silver sulfadiazine group and the other treatment groups, indicating that silver sulfadiazine significantly eliminated P. aeruginosa more effectively in the tissues than did the other two agents. All treatment modalities were sufficient to prevent the P. aeruginosa from invading to the muscle and from causing systemic infection. In conclusion, silver sulfadiazine is the most effective agent in the treatment of the P. aeruginosa-contaminated burn wounds; Acticoat can be considered as a treatment choice because of its peculiar ability of limiting the frequency of replacing wound dressings.

Administration, Topical↗

In vitro antimicrobial effect of chlorhexidine-impregnated gutta percha points on Enterococcus faecalis.

AIM: To evaluate the in vitro antimicrobial effect of chlorhexidine-impregnated gutta percha points, Roeko activ point (Roeko, Langenau, Germany) on Enterococcus faecalis. METHODOLOGY: Human maxillary premolar roots were prepared with.04 rotary ProFile instruments to a master apical file size 40, autoclave-sterilized and then infected with E. faecalis (ATCC 29212) for 3 weeks. Baseline controls were carried out verifying negligible effects of plain gutta percha cones on E. faecalis. Subsequent to intracanal placement of calcium hydroxide, 'activ points' or saline (positive control) and the 2-week incubation in 54 root specimens, dentine sampling at depths of 100 and 250 micro m was carried out using.04 rotary ProFile instruments at sizes 60 and 90 to assess the quantity of bacteria present. Inactivating agents were used prior to sampling and the colony-forming units (CFU) of E. faecalis were then plate-counted after culturing. Statistical analysis was completed using the paired t-test. RESULTS: In comparison to the positive control, treatment with calcium hydroxide (P = 0.000 and 0.000) or activ points (P = 0.000 and 0.002) produced significantly lower colony counts of E. faecalis at dentine depths of 100 and 250 micro m, respectively. Calcium hydroxide (2.10 x 102 CFU mL-1) was significantly more effective than activ points (1.58 x 103 CFU mL-1) at 100 micro m (P = 0.013), but not at 250 micro m (P = 0.353). Neither of these two medications was able to eliminate E. faecalis completely. CONCLUSIONS: Chlorhexidine-impregnated activ points did not possess an in vitro inhibitory activity strong enough to eliminate E. faecalis completely from infected dentinal tubules.

Anti-Infective Agents, Local↗

Mechanism of resistance of Bacillus subtilis spores to chlorhexidine.

Chlorhexidine diacetate (CHA) was rather more sporicidal at 20 degrees C to urea-dithreitol-sodium lauryl sulphate (UDS)-treated spores of Bacillus subtilis NCTC 8236 than to urea-dithiothreitol (UDT)-treated or normal (untreated) spores. UDS spores adsorbed more CHA from solution than did the other two forms. No differences in hydrophobicity, as determined by hydrophobic interaction chromatography (HIC) or bacterial adherence to hydrocarbon (BATH), could be detected between the three spore types. Germinating spores took up much less CHA than did outgrowing spores. Germinating cells were considerably more hydrophobic, as measured by the BATH technique, than outgrowing cells or normal spores. Chlorhexidine diacetate increased the apparent hydrophobicity of the two latter forms, but this effect could be partially reversed by subsequent exposure to a non-ionic surfactant.

Bacillus subtilis↗

Interaction of the bisbiguanides chlorhexidine and alexidine with phospholipid vesicles: evidence for separate modes of action.

Strains of Providencia stuartii with demonstrated resistance towards chlorhexidine did not show such resistance towards either of the related biguanide antiseptics, alexidine or vantocil. Alexidine promoted a significantly faster alteration in the permeability of Escherichia coli cell membranes towards various metal cations than chlorhexidine. Differential thermal analysis of various mixed lipid vesicles and pure phospholipid vesicles showed alexidine to share with vantocil the property of producing lipid phase separation and domain formation. It is suggested that the nature of the end-group on the biguanides affects the ability to produce lipid domains in cell membranes and this this might, in turn, affect activity and resistance patterns observed.

Anti-Bacterial Agents↗

Evaluation of antimicrobial interactions between chlorhexidine, quaternary ammonium compounds, preservatives and excipients.

The antimicrobial interactions of 49 combinations of chlorhexidine, quaternary ammonium compounds, preservatives and excipients were evaluated by the method of Berenbaum and the checkerboard titration method, with Staphylococcus aureus CIP 53154 and Escherichia coli CIP 54127 as test strains. MIC determinations were carried out as a preliminary step, and relative growth intensity was used to describe the bacteriostatic activity of surface-active agents (Amonyl 380 BA, Amonyl 671 SB). In the study of combinations, results were interpreted with Fractional Inhibitory Concentration indexes and represented by isobolograms. A fair correlation was shown between the method of Berenbaum and the checkerboard titration method. Combinations between chlorhexidine, cetrimonium bromide and benzalkonium chloride were synergistic or additive; combinations of antiseptics and preservatives were generally not antagonistic. The methods were also well adapted to the study of interactions involving surface-active agents, a critical problem in the formulation of topical antimicrobial agents.

Anti-Infective Agents, Local↗

The effect of chlorhexidine on defined, mixed culture oral biofilms grown in a novel model system.

In order to develop an improved method to evaluate antimicrobial agents for use in clinical dentistry, a constant-depth film fermenter (CDFF) has been used to generate biofilms of fixed depth comprising nine species of bacteria commonly found in dental plaque in health and disease. These bacteria were grown together initially in a conventional chemostat which was used to inoculate the CDFF over an 8 h period. Medium was then supplied directly to the CDFF and biofilms allowed to develop. The biofilms were then challenged with eight short pulses of two concentrations of chlorhexidine (0.0125 and 0.125% w/v). The lower concentration had a limited effect on the composition of the biofilms while a differential and substantial inhibition was obtained with a higher concentration. Actinomyces naeslundii was lost from the biofilm, and the viable counts of streptococci, Fusobacterium nucleatum and Porphyromonas gingivalis were inhibited by over three orders of magnitude by 0.125% chlorhexidine, whereas Veillonella dispar was only transiently affected. The findings were consistent with those from clinical studies of dental plaque, suggesting that this model would have a predictive value when evaluating novel antiplaque or antimicrobial inhibitors.

Anti-Infective Agents, Local↗

Antimicrobial activity of chlorhexidine diacetate and benzalkonium chloride against Pseudomonas aeruginosa and its response to biocide residues.

AIMS: The aims of this study were to evaluate the antimicrobial activity of chlorhexidine diacetate (CHX) and benzalkonium chloride (BZK) for strains of Pseudomonas aeruginosa exhibiting increased minimum inhibitory concentrations (MIC) for CHX, and to determine whether residues of chlorhexidine digluconate (CHG) and Hibiscrub (Hib, a formulation containing CHG) affect the susceptibility of P. aeruginosa to these biocides and a number of antibiotics. METHODS AND RESULTS: The bactericidal activity of CHX and BZK was evaluated for strains of P. aeruginosa exhibiting increased MIC for CHX with established suspension and surface disinfection tests. None of the strains of P. aeruginosa exhibiting raised MIC for CHX was less sensitive than the parent strain to CHX or BZK in either method. A test was designed to investigate the effects of dried CHG and Hib residues on P. aeruginosa cells. Exposure of P. aeruginosa to dried residues of CHG or Hib did not result in the organism becoming less sensitive to either biocide or a number of antibiotics. CONCLUSIONS: Pseudomonas aeruginosa strains with raised MIC to CHX were no less sensitive than the parent strain to CHX and BZK in bactericidal investigations. Exposure to dried residues of CHG and Hib did not render P. aeruginosa less sensitive to either of these agents or a number of antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: An increase in the MIC for a biocide in a micro-organism does not necessarily result in a failure of the biocide to effectively kill the organism. The residue that remains after the use of an antimicrobial agent can be at a far lower concentration than that initially applied and this study highlights the necessity for further investigations into the effect of residues, at low concentration, on bacterial populations and their role, if any, in the continued problem of antibiotic resistance.

Anti-Bacterial Agents↗