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PubMed2000

Development of resistance to chlorhexidine diacetate in Pseudomonas aeruginosa and the effect of a "residual" concentration.

Stable resistance in Pseudomonas aeruginosa NCIMB 10421 was obtained by step-wise exposure to gradually increasing concentrations of chlorhexidine diacetate (CHX). Repeated exposure to a proposed "residual" (sub-MIC) concentration of CHX also created stable resistance. Resistance was also developed by a single exposure to the "residual" concentration of CHX, but this was unstable. Similar experiments with Escherichia coli and CHX or cetylpyridinium chloride resulted in no significant increase in resistance. Antibiotic susceptibility profiles of the CHX-resistant P. aeruginosa cultures showed no cross-resistance, although some of the cultures were resistant to benzalkonium chloride.

Anti-Infective Agents, Local↗
PubMed2002

Antibiotic resistance as an indicator of bacterial chlorhexidine susceptibility.

The antibiotic and chlorhexidine (CHX) susceptibility of 70 distinct clinical isolates: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus (not MRSA), Streptococcus pyogenes and Enterococcus faecalis (10 of each) were tested using minimal bactericidal (MBC) and/or minimal inhibitory (MIC) concentrations. Non-fermentative bacteria tolerated CHX at high concentrations; Gram-positive cocci, especially S. pyogenes, were the most susceptible. We found a good correlation between CHX and antibiotic susceptibility in both MIC and MBC among Gram-negative bacteria, and mainly in MBC among Gram-positive bacteria. Resistance to ciprofloxacin, imipenem, cefotaxime, ceftazidime, gentamicin and aztreonam appeared to indicate increased CHX resistance among Gram-negative bacteria. This finding gives clinicians the ability to predict CHX susceptibility according to routine antibiotic resistance testing.

Chlorhexidine↗
PubMed2001

Methods for evaluating changes in skin condition due to the effects of antimicrobial hand cleansers: two studies comparing a new waterless chlorhexidine gluconate/ethanol-emollient antiseptic preparation with a conventional water-applied product.

BACKGROUND: Hand-cleansing products that are milder to the skin of health care personnel are being developed, but the available methodologies to appropriately evaluate these products and quantify differences are not generally being applied in well-controlled studies. METHODS: Two randomized, blinded, bilateral comparison studies evaluated skin condition during use of 2 antiseptic hand preparation products: a new 1% chlorhexidine gluconate (CHG)/61% wt/wt ethanol antiseptic hand preparation in a unique emollient system for waterless/brushless application and a conventional 4% CHG antimicrobial product that is applied with water and a scrub brush. Trained technicians applied treatments 6 times (for a surgical scrub study) or 24 times (for a personnel handwash study) daily to the hands of healthy volunteers during 5 days of controlled washing. An expert grader evaluated skin for dryness, erythema, and roughness. Subjects completed a self-assessment questionnaire on skin condition. Transepidermal water loss was measured by an evaporimeter, and the skin surface hydration level was measured by an electrical conductance meter. RESULTS: Fifty-eight subjects were enrolled in the 2 studies and received both treatments. In general, skin treated with the waterless CHG/ethanol product scored significantly (P <.004) better on evaluations of visual dryness and erythema and showed greater improvement in the level of hydration (P <.003). In the health care personnel handwash study, transepidermal water loss was less than that for skin treated with the conventional CHG product (P <.002). Subject assessments showed similar results (total score, P <.007). CONCLUSIONS: All 3 approaches of expert grader evaluation, subject assessment, and instrumentation were in concordance, demonstrating that the waterless CHG/ethanol product was gentler to skin than the conventional CHG product.

Adult↗
PubMed2001

Evaluation of a waterless, scrubless chlorhexidine gluconate/ethanol surgical scrub for antimicrobial efficacy.

A new waterless surgical hand preparation containing 1% chlorhexidine gluconate (CHG) and 61% ethyl alcohol was evaluated for antimicrobial efficacy in comparison with a standard 4% CHG surgical scrub and a 61% ethyl alcohol control. Clinical studies were based on the Tentative Final Monograph for Health-Care Antiseptic Drug Products (TFM) (proposed rule) and the Standard Test Method for Evaluation of Surgical Hand Scrub Formulations (ASTM E1115-91). Two randomized, blinded, well-controlled clinical studies involving 137 healthy subjects were conducted to evaluate the antimicrobial effectiveness of the CHG/ethanol hand preparation in producing an immediate and persistent reduction in the normal bacterial flora of the hands. The CHG/ethanol hand preparation was applied without scrubbing or the use of water, and a standard 4% CHG reference product was applied with a scrub brush in 2 traditional 3-minute surgical scrubs. In 1 study, a 61% ethanol vehicle control treatment was applied without scrubbing or use of water. During a 5-day period, each study subject performed a series of 11 surgical scrubs with 1 of the test treatments. After the first treatment on days 1, 2, and 5, surgical gloves were worn for 3 or 6 hours. Bacterial samples were taken with the glove-juice technique at 1 minute, 3 hours, and 6 hours after treatment. The immediate bactericidal effect of the CHG/ethanol hand preparation after a single application resulted in a 2.5-log reduction in normal flora. This bactericidal effect persisted throughout the studies and eventually increased to a 3.6-log reduction after the 11th scrub on day 5. The log reductions of the CHG/ethanol hand preparation proved to be significantly better (P <.05) than that of the 4% CHG product at each sampling interval on days 1 and 2 and the sampling at 6 hours on day 5 and significantly better than the 61% ethanol vehicle at all times. The combination of 1% CHG and 61% ethanol had significantly greater microbial reduction than either the 4% CHG (without ethanol) or the 61% ethanol vehicle (without CHG).

Adult↗
PubMed2001

The effect of sodium hypochlorite and chlorhexidine on cultured human periodontal ligament cells.

OBJECTIVE: The objective of this study was to examine the effects of sodium hypochlorite (NaOCl) and chlorhexidine (CHx) on cultured human periodontal ligament (PDL) cells in vitro. STUDY DESIGN: The effects of irrigation solutions on human PDL cells were evaluated by propidium iodide fluorescence cytotoxicity assay, protein synthesis assay, and mitochondrial activity. RESULTS: Both NaOCl and CHx were cytotoxic to human PDL cells in a concentration- and contact time-dependent manner. In addition, CHx inhibited protein synthesis in human PDL cells. Although NaOCl displayed cellular cytotoxicity, it showed no protein inhibition in the PDL cells. Furthermore, both NaOCl and CHx exhibited an inhibitory effect on mitochondrial activity on human PDL cells. CONCLUSIONS: This study suggests that these irrigation fluids may cause detrimental effects on vital tissues. Its clinical significance, however, needs to be evaluated further because concentration used, exposure time to the agent, and exposure surface area are important factors affecting the resulting effect.

Anti-Infective Agents, Local↗
PubMed2002

Substantive antimicrobial activity in chlorhexidine-treated human root dentin.

OBJECTIVE: The aim of this in vitro study was to assess the substantive antimicrobial activity of different medicaments in human root dentin. STUDY DESIGN: Canals of 98 roots were enlarged to standard size and medicated for 7 days with the following: (1) 2% chlorhexidine (CHX) gel, (2) 0.2% CHX gel, (3) 2% CHX solution, (4) Ca(OH)(2), (5) Ca(OH)(2)+ 0.2% CHX gel, (6) 2% CHX solution + a 25% CHX-containing controlled-release device, (7) saline, and (8) gel vehicle. After medication, canals were inoculated with Enterococcus faecalis for 21 days. Dentin samples were collected with Gates-Glidden burs into brain heart infusion broth, and bacterial growth was assessed with spectrophotometric analysis of optical density after 72 hours of incubation. RESULTS: Mean optical densities were significantly lower for groups with 2% CHX (1, 3, and 6) when compared with those of the controls (P < .05, analysis of variance with the Tukey test). Other groups did not differ significantly from the controls. CONCLUSIONS: Canal dressing for 1 week with 2% CHX may provide residual antimicrobial activity against E faecalis.

Analysis of Variance↗
PubMed2004

Salivary mutans streptococci and dental caries in three-year-old children after maternal exposure to chewing gums containing combinations of xylitol, sorbitol, chlorhexidine, and fluoride.

The aim of this study was to evaluate the effect of maternal use of chewing gums containing combinations of xylitol, sorbitol, chlorhexidine, and fluoride on salivary mutans streptococci (MS) counts and caries prevalence in the mothers' 3-year-old children. After screening 416 women with newborn babies, 173 mothers with high counts of salivary MS were randomly assigned into 3 experimental chewing gum groups containing (A) xylitol (n = 61), (B) chlorhexidine/xylitol/sorbitol (n = 55), and (C) sodium fluoride/xylitol/ sorbitol (n = 57). Mothers with low or medium MS counts formed a reference group (D) without any intervention (n = 232). The participants in the experimental groups were instructed to chew one piece of the gum for 5 min 3 times a day. The chewing regimen started when the child was 6 months old and was terminated 1 year later. The outcome measures were salivary MS counts and caries prevalence at the age of 3 years. Bacterial enumeration was carried out with a chair-side technique and caries (defs) was scored by clinical examination. Medium and high counts of salivary MS were found in 13%, 16%, and 22% in groups A, B, and C, respectively. The mean defs was 0.1 in group A, 0.2 in group B, and 0.4 in group C. The differences concerning salivary MS and caries were not statistically significant. The MS counts and caries prevalence in children of mothers with low MS counts (group D) were similar to those found in groups A and B. In conclusion, lower but non-significant levels of salivary MS and dental decay were observed in 3-year-old children to mothers who used high-content xylitol gums compared with those who used lower amounts of xylitol. The efficiency of this type of targeted intervention in a low-caries community may be questioned.

Adolescent↗
PubMed2006

Effects of single intratracheal exposure to chlorhexidine gluconate on the rat lung.

Chlorhexidine gluconate (CHX) is an antiseptic that has been widely used for disinfection of cutaneous wound and gingivae. Recently, a patient who inhaled CHX solution died from acute respiratory distress syndrome (ARDS). Although it is highly possible that direct pulmonary damage might be the cause of ARDS, there is no preclinical information about the pulmonary toxicity of CHX. In the current study, the acute direct action of CHX to the lung was evaluated in rats. We successfully exposed the left but not the right lung either to CHX at concentrations of 1%, 0.1%, and 0.01% or to saline using a curved-tip administration tube. At the higher concentrations of CHX (0.1% and 1%), severe congestion to the alveoli and capillaries and perivascular and intra-alveolar hemorrhages were observed 1 day after exposure. Aniline blue-stained collagen fibers with an infiltration of inflammatory cells were present 7 days after exposure. The fibrotic changes and intra-alveolar inflammatory cells had decreased but were still observed sporadically 28 and 84 days after exposure. These detrimental effects were more severe at 1% than at 0.1% CHX. No remarkable effect was observed after exposures to 0.01% CHX and saline. We were able to evaluate the time-course changes in the pulmonary toxicity of CHX by exposures limited to the left lung. It is highly possible that CHX at a concentration of more than 0.1% might directly induce ARDS when aspirated and reaching to the alveoli.

Animals↗
PubMed2006

Design and evaluation in vitro of controlled release mucoadhesive tablets containing chlorhexidine.

This investigation deals with the development of buccal tablets containing chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects in the oral cavity, and able to adhere to the buccal mucosa to give local controlled release of drug. A mucoadhesive formulation was designed to swell and form a gel adhering to the mucosa and controlling the drug release into the oral cavity. Some batches of tablets were developed by direct compression, containing different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing the amount ratio of these excipients in formulations, it is possible easily modulate the mucoadhesive effect and release of drug. The in vitro tests were performed using the USP 26/NF paddle apparatus, a specifically developed apparatus, and a modified Franz diffusion cells apparatus. This last method allows a simultaneous study of drug release rate from the tablets and drug permeation through the buccal mucosa. Similar tests have also been carried out on a commercial product, Corsodyl gel, in order to compare the drug release control of gel with respect to that of the mucoadhesive tablet, as a formulation for buccal delivery of CHX. While the commercial formulation does not appear to control the release, the formulation containing 15% w/w methocel behaves the best, ensuring the most rapid and complete release of the drug, together with a negligible absorption of the active agent as required for a local antiseptic action in the oral cavity.

Adhesiveness↗
PubMed1992

Rapid inactivation of infectious pathogens by chlorhexidine-coated gloves.

OBJECTIVE: Gloves containing chlorhexidine gluconate in an instant-release matrix on their inner surface (CHG gloves) were tested to determine their ability to rapidly inactivate infectious pathogens that may permeate or leak through the latex surface. DESIGN: CHG gloves were exposed for 1 to 10 minutes to blood or media containing infectious pathogens (e.g., bacteria, fungi, parasites, and viruses) as well as to lymphocytes and macrophages that are known to be the primary carriers of human immunodeficiency virus (HIV). Inactivation of pathogens was determined either by in vitro assay or in vivo infectivity. Stressed control and CHG glove fingers were submerged in a viral pool (retrovirus or bacteriophage) and after a set time, the glove interiors were checked for presence of permeated virions. RESULTS: CHG gloves rapidly inactivate all the pathogens tested including retrovirus and hepatitis B virus (90% to 100%). In the stressed glove fingers, live virus was detected in 26% of the control group but not in any of the CHG group. CONCLUSIONS: The use of CHG gloves may reduce the risk of exposure to infectious fluid-borne pathogens should the integrity of the latex barrier be compromised by overt failure or by permeation of viruses. Rapid destruction of lymphocytes and macrophages may facilitate inactivation of HIV associated with these cells. Tests have shown that CHG coating does not alter physical properties of the glove, and, furthermore, CHG gloves do not show potential for dermal irritation or sensitization.

Animals↗
PubMed2001

Prophylactic chlorhexidine oral rinse decreases ventilator-associated pneumonia in surgical ICU patients.

BACKGROUND: Pneumonia is one of the most common nosocomial infections in hospitalized patients. The risk of nosocomial pneumonia increases with age, severity of acute illness and preexisting co-morbid conditions. Ventilator-associated pneumonia (VAP) significantly increases morbidity, length of stay, resource utilization and mortality. The purpose of this study was to determine whether adherence to a ventilator weaning protocol (WP) and the use of chlorhexidine gluconate (CH) oral rinse for oral hygiene would decrease the incidence of VAP in surgical ICU patients. METHODS: A prospective study was conducted over a period of 10 months (October 1998-July 1999) in surgical ICU patients requiring mechanical ventilation (n = 95). During the first 5 months, a WP was applied to all patients requiring mechanical ventilation. During the following 5 months, a CH 0.12% oral rinse administered twice daily was added to the protocol, initiated on ICU admission in all intubated patients. The data collection included age, gender, race, risk factors, co-morbid conditions, severity of the acute illness (APACHE II) at admission, duration of ventilation, ICU and total-hospital length of stay, and incidence of VAP and in-hospital mortality rates. Both WP and WP+CH groups were compared using the National Nosocomial Infection Surveillance (NNIS) and hospital databases as historic controls. RESULTS: The institution of the WP alone led only to a slight decrease in the incidence of VAP but a significant reduction in the median duration of mechanical ventilation by 40% (4.5 days, p < 0.008). The addition of CH to the WP led to a significant reduction and delay in the occurrence of VAP (37% overall, 75% for late VAP, p < 0.05). The median duration of mechanical ventilation in this group was similar to that of the WP group. There was no significant difference in the overall hospital or ICU length of stay between the groups. CONCLUSIONS: Improved oral hygiene via topical CH application in conjunction with the use of a WP is effective in reducing the incidence of VAP and the duration of mechanical ventilation in surgical ICU patients.

Aged↗
PubMed2006

Pharmacokinetics of chlorhexidine gluconate 0.02% in the rabbit cornea.

PURPOSE: The aim of this study was to determine the pharmacokinetic parameters of chlorhexidine gluconate (CHG) in the rabbit cornea. METHODS: Each eye of 16 New Zealand white rabbits were topically instilled with 50 microL of CHG 0.02% eye drops twice with a 5-min interval. Four (4) corneas of 2 rabbits were harvested at each time point. The concentration of CHG in the cornea was determined with high-performance liquid chromatography (HPLC) and 387 software to simulate the pharmacokinetic parameters. RESULTS: The concentration of CHG in the cornea displayed an open two-compartment model. Tmax was 13.75 min, Cmax 0.713 microg.g1, clearance rate 1.64 microg.g-1.min-1, and t1/2alpha, t1/2beta, and t1/2ka was 2.65, 48.72, and 2.67 min, respectively. CONCLUSIONS: The concentration of CHG in the rabbit cornea could be determined by means of HPLC. The maximum concentration of CHG in the corneal tissue was much higher than the trophozoite minimum amoebicidal concentration (TMAC) in vitro.

Administration, Topical↗
PubMed2000

Cytological changes in chlorhexidine-resistant isolates of Pseudomonas stutzeri.

Transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy-dispersive analysis of X-ray (EDAX) have been used to examine chlorhexidine diacetate (CHA)-sensitive and -resistant isolates of Pseudomonas stutzeri and to determine the effects of CHA on the cells. Significant differences were observed in the structure, size and elemental composition of CHA-sensitive and -resistant cells. Treatment with CHA produced considerably greater changes in CHA-sensitive cells, with widespread peeling of the outer membrane, a substantial loss of cytoplasmic electron-dense material and extensive lysis. Cells from the resistant isolates showed no blebbing of the outer membrane and no structural damage. X-ray mapping confirmed the difference in CHA uptake between CHA-sensitive and CHA-resistant cells. It is proposed that changes in the outer membrane form a major mechanism of resistance to CHA in P. stutzeri.

Chlorhexidine↗
PubMed2003

Effects of ortho-phthalaldehyde, glutaraldehyde and chlorhexidine diacetate on Mycobacterium chelonae and Mycobacterium abscessus strains with modified permeability.

The mechanisms of the mycobactericidal action of ortho-phthalaldehyde (OPA), glutaraldehyde (GTA) and chlorhexidine diacetate (CHA) were investigated using mycobacterial spheroplasts of two reference strains, Mycobacterium chelonae NCTC 946, Mycobacterium abscessus NCTC 10882 and two GTA-resistant strains, M. chelonae Epping and M. chelonae Harefield. Transmission electron microscopy of the spheroplasts revealed an altered cell wall structure compared with the parent cells. Structural alterations resulting from the spheroplasting process were in part correlated to a loss of lipid content. Low concentrations of CHA induced protein coagulation in M. chelonae NCTC 946 spheroplasts, which also exhibited the highest loss of free non-polar lipids. Higher concentrations of CHA were required to produce similar results to the other spheroplasts investigated in which there was a less substantial decrease in lipid content. OPA (0.5% w/v) readily penetrated the residual cell wall and cytoplasmic membrane, producing significant protein coagulation in M. chelonae NCTC 946. GTA (0.5% v/v) induced a similar effect but to a lesser extent. Pre-treatment of the spheroplasts with OPA and GTA and their subsequent suspension in water demonstrated that GTA was a more potent cross-linking agent. This protective effect of GTA results from extensive cross-linking of amino and/or sulphydryl side-chain groups of proteins. The rapid mycobactericidal effect of OPA probably arises from its more efficient penetration across biological membranes. Mycobacterial spheroplasts represented a useful cellular model with an altered cell wall permeability. This study also showed the importance of the mycobacterial cell wall in conferring intrinsic resistance to CHA.

Cell Wall↗
PubMed2006

Comparative study of the antimicrobial activity of bis(Nalpha-caproyl-L-arginine)-1,3-propanediamine dihydrochloride and chlorhexidine dihydrochloride against Staphylococcus aureus and Escherichia coli.

OBJECTIVES: The aim of this study is to gain insight into the mechanism of the antimicrobial action of a novel arginine-based surfactant, bis(N(alpha)-caproyl-L-arginine)-1,3-propanediamine dihydrochloride [C(3)(CA)(2)]. METHODS: To this end, we compared its effects against Staphylococcus aureus and Escherichia coli with those caused by the commercial and widely known antiseptic, chlorhexidine dihydrochloride (CHX). RESULTS: Both disrupted the cell membrane of the target bacteria to cause potassium leakage and morphological damage. The effect of C(3)(CA)(2) on E. coli was concentration dependent, causing loss of membrane potential and membrane integrity leading to cell death, whereas CHX did not have these effects on E. coli. The effect of C(3)(CA)(2) on S. aureus was the formation of mesomes and cytoplasmic clear zones, but the loss of membrane potential and membrane integrity was slightly lower than that with CHX. CONCLUSIONS: We propose that C(3)(CA)(2) acts preferentially against Gram-negative bacteria through strong initial binding to the surface lipopolysaccharides and subsequently partitioning into the cell membrane to cause membrane damage, followed by cell death.

Anti-Bacterial Agents↗
PubMed1990

Use of a chlorhexidine dressing to reduce microbial colonization of epidural catheters.

We performed a prospective randomized controlled trial to assess the efficacy of a chlorhexidine dressing in reducing the microbial flora at the insertion site of epidural catheters. These catheters were used for acute pain management and were dressed either by a standardized method or with a CHX/urethane sponge composite. Microbial colonization of the catheter developed in 9 of 31 controls (29.0%) and 1 of 26 (3.8%) catheters with the CHX dressing (P less than 0.05%). The CHX dressing caused no adverse effects. The data suggest that delivery of antiseptic to the catheter wound site reduces catheter colonization with a possible reduction in the risk of epidural catheter-related infection.

Analgesia, Epidural↗
PubMedDate not supplied

Wet disc testing of mafenide hydrochloride, chlorhexidine gluconate, and triple antibiotic solution against bacteria isolated from burn wounds.

Various antimicrobial solutions for topical use on burn wounds tested, in vitro with a newly described wet disc assay, for their activity against bacterial isolates from patients with burns. The antimicrobial activity of triple antibiotic solution was shown to reside in the neomycin component. The activity of 2.5% mafenide hydrochloride solution was equal to that of 4% mafenide HCl and could be used clinically with significant savings and perhaps, fewer side effects. Chlorhexidine gluconate had broad antimicrobial activity in an 0.05% solution in water; however, dissolving the active ingredient in saline nullified its activity significantly. The wet disc assay appears to be a useful means by which to assess the efficacy of solutions for topical use.

Bacitracin↗