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Quantitative assessment of the effect of 0.05% chlorhexidine on rat articular cartilage metabolism in vitro and in vivo.

Wound infection remains a problem. Syringe and needle jet lavage of chlorhexidine gluconate 0.05% removed or killed 99.8% of contaminating bacteria within 1 minute in a wound model. In clinical use, however, possible toxicity to articular cartilage is a concern. In an established intact rat patella model in vitro, 1 minute of exposure to chlorhexidine 0.05% and chlorhexidine jet lavage did not significantly alter cartilage metabolism. A 1-hour exposure decreased metabolic activity. In vivo, a 30-minute exposure with or without rinsing produced no impairment of metabolic activity 6 weeks later, suggesting that cartilage has the potential for biological recovery. However, injecting and leaving chlorhexidine 0.05% in the joints was detrimental to the metabolic activity of the articular cartilage as assessed 6 weeks later. Thus, chlorhexidine gluconate 0.05% could be used on normal articular cartilage. Any potential damage from prolonged exposure can be avoided by rinsing after 1 minute.

Animals↗

Use of intraperitoneal 5-fluorouracil and chlorhexidine for prevention of recurrence of perforated colorectal carcinoma in a rat model.

PURPOSE: Colorectal cancer is a prevalent and mortal disease, resulting in nearly 55,000 deaths in the United States annually. Preoperative or intraoperative spillage of tumor cells because of perforation occurs in up to 10 percent of cases. When this spillage occurs, the chance of recurrence and death is dramatically increased. METHODS: In an effort to reduce the chance of recurrence and death, we used a rat model to evaluate the efficacies of intraperitoneal 5-fluorouracil and chlorhexidine in reducing the incidence of recurrence. Rats were injected with 10 mg/kg azoxymethane subcutaneously weekly for 12 weeks to induce colorectal cancers. At 20 weeks, subtotal colectomies were performed on rats with colorectal tumors and without peritoneal implants or liver metastases. At the time of surgery, a cut portion of the tumor was placed in the abdomen for 30 minutes; the rats then randomly received peritoneal irrigation with 5-fluorouracil, chlorhexidine, or sterile water (control). Eight weeks postoperatively a necropsy was performed. At that time, obvious and suspected recurrences and the anastomotic area were sampled for histologic evaluation. RESULTS: Significant differences were seen with chlorhexidine vs. water for gross tumor (P = 0.05) and microscopic tumor (P < 0.05). 5-Fluorouracil showed a greater rate of abscess formation vs. both control and chlorhexidine (P > 0.05). CONCLUSIONS: Use of chlorhexidine intraperitoneal therapy at the time of the operation for perforated colorectal cancer significantly decreases the frequency of gross tumor recurrence but not total recurrences. Intraperitoneal 5-fluorouracil does not significantly decrease recurrence and may increase the risk of abscess when used intraoperatively.

Animals↗

Pin site care in external fixation sodium chloride or chlorhexidine solution as a cleansing agent.

INTRODUCTION: Pin site infection is the most common complication using external fixators. This study investigated the differences in pin site infections, antibiotic use, pain, and complications using sodium chloride and chlorhexidine solution as cleansing agent in patients operated on by the hemicallotasis technique for knee deformities. MATERIALS AND METHODS: The prospective study included 49 consecutive patients: 2 mg/ml chlorhexidine solution was used as cleansing agent in 30 patients (120 pins) and 9 mg/ml sodium chloride in 19 patients (76 pins). We evaluated the status of the pin sites, pain (VAS), uses of antibiotic and analgesic agents, and any complications (infections were graded according to the Checketts-Otterburns classification). Bacterial cultures were performed from each pin site at 1, 6, and 10 weeks and from the pins at removal. RESULTS: Grade 1 infection was found in 14% of the sodium chloride group and in 8.5% of the chlorhexidine group, and grade 2 infection in and 3% and 0.5%, respectively. With sodium chloride there was a significantly higher relative risk for positive cultures (1.7) and for the presence of Staphylococcus aureus (3.3). The chlorhexidine group required significantly fewer antibotics reported significantly less pain at weeks 6 and 10. CONCLUSIONS: Chlorhexidine solution (2 mg/ml) as cleansing agent in pin site care is preferable to sodium chloride in patients operated on by the hemicallotasis technique.

Adult↗

Monitoring of buccal epithelial cells by alkaline comet assay (single cell gel electrophoresis technique) in cytogenetic evaluation of chlorhexidine.

During the last few years, there has been increasing interest in buccal epithelial cells for cytogenetic evaluation of different materials. In the present study, the use of these cells and peripheral lymphocytes for cytogenetic evaluation of chlorhexidine digluconate (CHX) with comet assay (single cell gel electrophoresis, or SCGE) is reported. This technique detects DNA strand breaks in individual cells in alkaline conditions. Thirteen volunteers were requested to rinse their mouths with 0.12% CHX solution for 18 days. Buccal epithelial cells and peripheral blood lymphocytes were obtained from all participants at baseline and the end of the experimental period. One hundred cells per subject were analysed for the DNA damage. A statistical increase was observed in the damaged buccal and blood cells after the CHX application. The mean grade of damage in buccal cells was statistically different from that in blood cells. Due to minimal absorption of chlorhexidine into the tissues and low concentrations of free chlorhexidine in the oral cavity, the DNA damage produced by chlorhexidine in lymphocytes was lower than in buccal epithelial cells. As chlorhexidine does not accumulate in the body, the frequencies of DNA damage could be transient. Detected DNA damage after CHX use might be the indication of an earlier effect, before DNA repair begins, and could be reversible.

Adult↗

The effect of chlorhexidine gluconate irrigation on the root canal flora of freshly extracted necrotic teeth.

Forty freshly extracted teeth with necrotic pulps were endodontically treated under simulated clinical conditions. Bacteriologic samples were obtained before during, immediately after, and 24 hours after instrumentation, irrigation, and medication either with 0.2 percent chlorhexidine gluconate or with sterile saline. There was a highly significant (p less than 0.0049) reduction in microorganisms in the chlorhexidine-treated specimens after the instrumentation and irrigation procedures. Further significant reductions were noted after intracanal dressing of the teeth for 24 hours with the chlorhexidine gluconate solution. The teeth treated with saline also demonstrated a generalized decrease in flora after the biomechanical procedures. However, there was an absolute increase in numbers of microorganisms for 80 percent of the uniradicular and 50 percent of the multiradicular specimens when no intracanal, antimicrobial dressing was applied. It was concluded that chlorhexidine gluconate in a 0.2 percent solution can be an effective antimicrobial agent when used as an endodontic irrigating solution and that as an intracanal, interappointment dressing, chlorhexidine helps to further reduce bacteria remaining within the root canal system.

Bacteria↗

Effects of chlorhexidine mouthrinse on oral health in patients with acute leukemia.

The effects of chlorhexidine mouthrinses, used as a supplement to mechanical oral hygiene measures, were studied in patients receiving treatment for acute leukemia. Twenty-eight patients were randomly divided into two groups. During two periods, when the patients were taking medication for the leukemia, one group rinsed with a 0.2% chlorhexidine solution twice daily and the other group did not. Chlorhexidine had no effects of any clinical significance on parameters such as number of days with fever, number of oral lesions, plaque score, gingival bleeding score, or occurrence of candidiasis. There was, however, an increased number of patients who had a burning sensation in the mouth, and a tendency toward increased numbers of salivary enterococci, enterobacteria, and/or Pseudomonas in patients who rinsed with chlorhexidine. The results of the present study do not support the use of chlorhexidine mouthrinses in patients who are able to maintain good oral hygiene by mechanical means during their illness.

Adolescent↗

Effect of nystatin and chlorhexidine digluconate on Candida albicans.

Polyene antibiotics such as nystatin and amphotericin B are among the most widely recommended drugs for use against oral candidiasis. It is also generally accepted that chlorhexidine gluconate is an appropriate adjunct or an alternative to specific antimycotic drugs. The aim of the present study was to examine the effect of the combination of nystatin and chlorhexidine digluconate on Candida albicans in vitro. The minimum inhibitory concentration (MIC) value for the combination of the two drugs was found to be significantly higher than the values for each of the drugs alone, approximately 33 times the MIC value for the nystatin solution and 4 times the value for chlorhexidine digluconate. The results of the MIC study and the presence of a precipitate in all combinations of nystatin and chlorhexidine digluconate showed that the combination of the drugs is not effective in vitro against Candida albicans. The most likely reason is that a low solubility chlorhexidine-nystatin salt is formed, thus rendering the combined drug complex ineffective as an antibiotic agent.

Candida albicans↗

Chlorhexidine inactivation by saliva.

Chlorhexidine mouth rinsing is commonly used for oral flora reduction. Indigenous microorganisms (viridans streptococci) are significantly suppressed, while "hospital-acquired" gram-negative bacilli are not affected in vivo. To explain the discrepancies between good in vitro and poor in vivo activity of chlorhexidine, minimum bactericidal concentration values for 120 isolates were studied by means of a standard dilution method in fresh whole saliva, broth, and glucose 5%. Both saliva and broth significantly reduced the bactericidal activity of chlorhexidine against all microorganisms tested as compared to glucose 5% (p less than 0.01). Minimum bactericidal concentrations for indigenous flora were significantly lower than the values obtained for the "hospital-acquired" microorganisms (p less than 0.05). These observations of chlorhexidine inactivation by saliva may explain why chlorhexidine mouth rinsing is of limited value in decontaminating the oral cavity.

Analysis of Variance↗

An investigation into in vitro methods for the detection of chlorhexidine resistance.

During an outbreak of catheter-related urinary tract infection, due to Proteus mirabilis, it was suggested that the epidemic strain was resistant to chlorhexidine. In this study, the minimum inhibitory concentrations (MICs) of chlorhexidine to the epidemic Pr. mirabilis and other laboratory isolates were tested in different media. Results were compared with killing times using 1/4 strength Ringers solution, normal human urine and the in vivo killing times in two patients' catheter bags. It was found that the MIC test was unreliable in the assessment of chlorhexidine resistance as it was dependent on the medium used, the inoculum size, and the age of the culture. The test which gave results closest to the in vivo experiments was the killing curve in normal human urine. It is concluded that chlorhexidine resistance is a complex phenomenon which is difficult to evaluate. If in vitro tests are to be used to evaluate the clinical relevance of reduced sensitivity to chlorhexidine, they must mimic the in-use conditions as closely as possible.

Chlorhexidine↗

Prevention of intraoperative wound contamination with chlorhexidine shower and scrub.

In a prospective, controlled, clinical trial, we found that preoperative showering and scrubbing with 4% chlorhexidine gluconate was more effective than povidone-iodine or triclocarban medicated soap in reducing skin colonization at the site of surgical incision. Mean log colony counts of the incision site were one half to one log lower for patients who showered with chlorhexidine compared to those who showered with the other regimens. No growth was observed on 43% of the post shower skin cultures from patients in the chlorhexidine group compared with 16% of the cultures from patients who had povidone-iodine showers and 5% of those from patients who used medicated soap and water. The frequency of positive intraoperative wound cultures was 4% with chlorhexidine, 9% with povidone-iodine and 14% with medicated soap and water. This study demonstrates that chlorhexidine gluconate is a more effective skin disinfectant than either povidone-iodine or triclocarban soap and water and that its use is associated with lower rates of intraoperative wound contamination.

Baths↗

A wound healing study of chlorhexidine digluconate in guinea pigs.

Formulations with and without chlorhexidine digluconate, a broad-spectrum antimicrobial, were tested for their effects on the healing of incisions and abrasions surgically induced in male guinea pigs. Formulations containing chlorhexidine were a skin cleanser formulation (4% w/v), a tinted tincture (0.5% w/v), and both 0.5 and 4% w/v aqueous solutions. Control materials were saline, and both the skin cleanser and the tincture formulations without chlorhexidine. Presurgical preparation was limited to closely clipping the hair and wiping each wound area with saline to remove loose hair, dander, and dirt. Each incision and abrasion was irrigated with its assigned material at surgery and daily thereafter until necropsy. Guinea pigs were killed on Days 3, 6, 9, 14, and 21, and wound sites were removed and fixed for histologic evaluation of healing. Daily progress of the wound healing appeared comparable for all treatment groups and there was no gross evidence of treatment effects at necropsy. For the animals with incisions, there were no remarkable histological differences among the treatment groups at Day 3. At Days 6 and 9, the two formulations containing 4% chlorhexidine produced a slight delay in healing when compared with the other treatment groups. These differences decreased with time, and by Day 21, there were no remarkable histological differences among animals of the various treatment groups. For the animals with abrasions, all treatment groups with and without chlorhexidine had slightly delayed healing compared to the saline control animals on Day 3 and 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Randomized study of vaginal chlorhexidine disinfection during labor to prevent vertical transmission of group B streptococci.

OBJECTIVE: To evaluate the effect of vaginal disinfection with chlorhexidine gel during labor on vertical transmission of group B streptococcus, as a method to prevent vertical transmission and subsequent neonatal early onset group B streptococcal disease. STUDY DESIGN: A prospective study with randomization of 1020 parturients to one of three groups as soon as labor started. In all parturients, anus, introitus and cervix were cultured semiquantitatively. Two groups were treated double-blindly with 10 ml of either a 0.3% chlorhexidine gel or a placebo gel, applicated around the portio and into the fornices. If labor still continued, a second application was given after 10 h. The third group received no treatment. Ear, pharynx and umbilicus of all newborns were also cultured semiquantitatively. RESULTS: Nine hundred and eighty one women were evaluated. The overall incidence of group B streptococcal carriership was 19.4%. Vertical transmission was 52.4% in the chlorhexidine group, 71.4% in the placebo group and 66.7% in the control group (P = 0.069). When testing the transmission rates for the chlorhexidine versus the combined placebo plus control group (69.3%), the difference was 16.9% (P = 0.026). CONCLUSION: Vaginal disinfection with a chlorhexidine gel during labor modestly reduces group B streptococcal vertical transmission. Because the method is cheap, simple and safe, it should be considered for routine use. Our results indicate that it may reduce the incidence of early onset group B streptococcal sepsis by 2-32%.

Anti-Infective Agents, Local↗

A randomized trial that compared povidone iodine and chlorhexidine as antiseptics for vaginal hysterectomy.

OBJECTIVE: The purpose of this study was to compare the efficacy of chlorhexidine and povidone iodine for cleansing the operative field for vaginal surgery. STUDY DESIGN: This was a randomized controlled trial that compared 10% povidone iodine and 4% chlorhexidine gluconate as surgical scrubs. Our primary end point was the proportion of contaminated specimens (defined as total bacterial colony counts of >/=5000 colony-forming units) per group found throughout the surgical procedures. All patients received standard infection prophylaxis that included preoperative intravenous antibiotics. Immediately before antibiotic administration and baseline aerobic and anaerobic cultures of the vaginal flora were obtained, which were followed by cultures at 30 minutes after the surgical scrub and hourly thereafter throughout each patient's surgery. RESULTS: A total of 50 patients were enrolled between October 2002 and September 2003. There were no differences between the povidone iodine (n = 27) and chlorhexidine (n = 23) groups with respect to age, race, exogenous hormone use, body mass index, gravity, parity, preoperative mean colony counts, or operative time. Among the first set of intraoperative specimens (which were obtained 30 minutes after the surgical scrub), 63% of the cultures (17/27) from the povidone iodine group and 22% of the cultures (5/23) from the chlorhexidine group were classified as contaminated ( P = .003; relative risk, 6.12; 95% CI, 1.7, 21.6). Subsequent cultures failed to demonstrate significant differences. CONCLUSION: Chlorhexidine gluconate was more effective than povidone iodine in decreasing the bacterial colony counts that were found in the operative field for vaginal hysterectomy.

Adult↗

Effect of subinhibitory concentration of chlorhexidine on Streptococcus agalactiae virulence factor expression.

The aim of the present study was to investigate the effect of chlorhexidine at subinhibitory concentration (50% minimal inhibitory concentration (MIC)) on the growth, cytolysin expression and phagocytosis of Streptococcus agalactiae ATCC 13813. Bacterial growth with and without chlorhexidine treatment was monitored by turbidity measurements, and exocytolysins were estimated by neutral red uptake assay by the McCoy cell line. The phagocytic process was evaluated using luminol-enhanced chemiluminescence to follow the respiratory burst of polymorphonuclear neutrophils exposed to bacteria. Chlorhexidine-treated culture did not exhibit a detectable decrease in cell growth, and no statistically significant reduction in the respiratory burst of polymorphonuclear neutrophils was observed. However, growth in the presence of chlorhexidine resulted in a significant reduction of S. agalactiae exocytolysins. Although 50% MIC of chlorhexidine did not interfere with S. agalactiae growth and phagocytosis, the knowledge that this concentration was still able to alter some bacterial virulence parameters may be useful in its therapeutic applications.

Animals↗

Assay of stability, free and total concentration of chlorhexidine in saliva by solid phase microextraction.

This paper presents the development and application of a solid phase microextraction method for the full investigation of chlorhexidine interaction with saliva during a pharmacokinetic study: chemical stability, binding to proteins, free concentration, total concentration and kinetics of elimination after oral administration. Only 0.1 mL sample were needed for each time point and the concentration of salivary proteins was determined as well. It was shown that chlorhexidine remained stable in the oral cavity for at least 9 h and high concentrations of the drug (2 microg/mL total) were still present even 8 h after mouthrinsing. Supplementary facts were uncovered: while the total concentration followed first-order elimination kinetics, the free concentration remained almost constant for several hours; this showed that the oral cavity acted like a reservoir that slowly released the drug. It was also revealed that following oral administration of chlorhexidine, the normal composition of saliva changed for a few hours, probably as a physiological response to the bitter taste of the medicine. The method had a wide linear range (0.1-40 microg/mL free chlorhexidine) that was perfectly suitable for the study of chlorhexidine retention in the oral cavity. Separation and quantitation were achieved by liquid chromatography coupled to mass spectrometry; no interference from endogenous compounds was observed. This selective and sensitive solid-phase microextraction (SPME) approach for monitoring the free and total concentration of a drug, as well as the concentration of proteins that bind that drug, should prove to be more useful for pharmacokinetic studies than classic methods that only provide the total concentration as a final result.

Chlorhexidine↗

In vitro assessment of the immediate and prolonged antimicrobial action of chlorhexidine gel as an endodontic irrigant against Enterococcus faecalis.

OBJECTIVE: The aim of this study was to assess in vitro the antimicrobial activity of 2% chlorhexidine gel against Enterococcus faecalis , comparing it to other endodontic irrigants (2% chlorhexidine liquid and 5.25% sodium hypochlorite). STUDY DESIGN: Eighty roots of human mandibular premolars were prepared by serial instrumentation technique, autoclaved, and contaminated for 7 days with E faecalis monocultures. The roots were then divided into 5 groups according to the irrigant substance used during the standardized biomechanical preparation. In order to evaluate the antimicrobial action of the irrigant substances, 3 microbial samples were taken: initial (before the biomechanical preparation); post-treatment (immediately after the biomechanical preparation), and final (7 days after the biomechanical preparation). The microbiological samples were plated to count the colony-forming units (CFU). RESULTS: The 2% chlorhexidine gel and 2% chlorhexidine liquid significantly reduced the E faecalis CFU in the post-treatment and final microbiological samples. The 5.25% sodium hypochlorite also reduced the E faecalis CFU immediately after the root canal instrumentation, but it was not able to keep the root canal free of detectable E faecalis in the final sample. CONCLUSIONS: The 2% chlorhexidine gluconate (gel and liquid) antimicrobial ability was more effective than 5.25% sodium hypochlorite in keeping low CFU of E faecalis for 7 days after the biomechanical preparation.

Anti-Infective Agents, Local↗

Influence of chlorhexidine species on the liquid crystalline structure of vehicle.

The aim of this study was to investigate the influence of three chlorhexidine species, chlorhexidine base and its salts (diacetate and digluconate), on the physico-chemical features of liquid crystalline systems and on drug transport through lipophilic membranes. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13--15)) was selected for the preparation of the liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were prepared. The liquid crystalline systems were characterized using polarizing microscopy, small-angle neutron scattering and transmission electron microscopy. Membrane transport was also examined. The addition of chlorhexidine species to the liquid crystalline system modified the structure of the liquid crystalline system. As a result of liquid crystal--drug interaction, the solubility of chlorhexidine base and its diffusion through lipophilic membranes increased in comparison with those of the chlorhexidine salts.

Chemical Phenomena↗

Effects of topical chlorhexidine applied to the rabbit nasal mucosa.

OBJECTIVE: To search the effects of administration of various concentrations of a wide-spectrum antimicrobial agent, chlorhexidine, to the nasal mucosa. MATERIAL AND METHODS: About 0.20, 0.12, 0.06 and 0.03% concentrations of chlorhexidine gluconate were applied to the rabbit nasal mucosa as one puff twice a day throughout 5 days. Another group, treated with serum saline to the nose, behaved as the control group. On the fifth day following drug administration, specimens were taken from nasal mucosa of the rabbits and examined under light microscope. RESULTS: As a result of comparison between drug treated group and control group, with increasing drug concentrations progressively increased neutrophil infiltration in mucosa, ciliary loss in cells, and occasional metaplasia were observed. CONCLUSION: There is a linear, positive and strong association between concentrations of chlorhexidine and its irritative effects on rabbit nasal mucosa. While 0.20 and 0.12% concentrations of chlorhexidine cause excess irritation on the nasal cavity, 0.06 and 0.03% concentrations of chlorhexidine gluconate causes lower irritation and effects on the animals which have experimentally induced rhinosinusitis must be evaluated.

Aerosols↗