Efficacy of an alcohol-based healthcare hand rub containing synergistic combination of farnesol and benzethonium chloride

Healthcare workers are required to disinfect the hands several times a day using hand disinfectants, which leads to chronic hand exposure to high levels of antimicrobials contained in the disinfectants, which could compromise the skin integrity. This problem may be addressed by developing hand disinfectants containing synergistic combinations of small amounts of antimicrobials and other agents. The synergistic effect of farnesol and essential oils with several antimicrobials was studied in vitro to select an effective antimicrobial system in preservative concentration for use in healthcare hand rub. Farnesol and lemon oil showed synergistic activity against S. aureus, in combination with benzalkonium chloride and benzethonium chloride, but not with other antimicrobials studied. All essential oils studied showed synergy with benzethonium chloride against Staphylococcus aureus and Escherichia coli. An alcohol-based healthcare hand rub (ZBF hand rub) containing this unique synergistic combination of farnesol and benzethonium chloride was then developed and its efficacy as a healthcare hand rub was evaluated in human volunteers according to the US FDA-TFM protocol using Serratia marcescens as a marker organism. The ZBF hand rub showed a 3.22 log(10) reduction in the microbial count after the first application and a 5.49 log(10) reduction after the tenth application in vivo and exceeds the US FDA-TFM criteria for healthcare hand rub. The ZBF hand rub did not irritate the hands when tested on human volunteers when applied 10 times everyday for five consecutive days. The ZBF hand rub exhibits more than 5.5 log(10) reduction in the microbial count within 15s and more than 2.8 log(10) reduction in the two types of viruses tested within 30s in vitro. When evaluated in an in vitro pig skin model, the ZBF hand rub shows better prolonged activity (20-35 min post-application) against transient bacteria (S. aureus and E. coli) compared to other alcohol-based hand rubs. These findings suggest that the use of the ZBF hand rub amongst health care workers may lower the risk of chronic hand exposure to high levels of antimicrobials without compromising the efficacy.     

In vivo efficacy of an alcohol-based surgical hand disinfectant containing a synergistic combination of ethylhexylglycerin and preservatives

Alcohol-based surgical hand disinfectants are widely available in healthcare settings. Some currently marketed alcohol-based products use active concentrations of antimicrobials to achieve the required efficacy, raising the risk for exposure to potentially irritating levels of antimicrobials. This study compares the in vitro and in vivo efficacy of an alcohol-based surgical hand preparation containing 70% ethanol and preservative levels of chlorhexidine gluconate (CHG) and benzalkonium chloride (BZK) in synergistic combination with ethylhexylglycerin (Surgicept) with a surgical hand disinfectant containing 61% ethanol and 1% CHG (Avagard). The in vivo efficacy of Surgicept and Avagard was evaluated in volunteers using the Tentative Final Monograph method of the Food and Drug Administration (FDA), and their prolonged effect against transient pathogens was compared using a pig skin model. Surgicept exceeded the FDA requirements for surgical hand antiseptic with mean log(10) reductions of 2.36, 3.3 and 3.54 in resident flora 1 min after initial application, and showed a persistent effect with mean log(10) reductions of 2.23, 2.73 and 3.3, 6h post application on days 1, 2 and 5, respectively. Surgicept showed a superior prolonged effect against transient bacteria compared with Avagard. Surgicept (70% alcohol and preservative levels of CHG and BZK) may provide similar in vivo efficacy as Avagard (61% ethanol and 1% CHG).     

Provision of alcohol hand rub at the hospital bedside: a case study

A pilot study was performed on a 28-bed acute hospital ward, promoting hand disinfection by providing Sterillium alcohol hand rub at the bedside. Bottles of Sterillium with pump dispensers were attached to the end of each patient's bed, next to the observation charts. Posters promoting the use of the product were prominently displayed and several ward staff attended a presentation on the effectiveness of Sterillium. Although this was a small study, Alert Organism rates during the three-month trial indicated a reduction in methicillin-resistant Staphylococcus aureus (MRSA) incidence and an increased Clostridium difficile incidence. Several other factors that may have influenced the study outcomes will be discussed. There were no health and safety problems during the trial, but other issues were identified which have implications for introducing the bedside rub on a hospital wide basis, including the type of holder used, logistical arrangements and the staff and patient information requirements. The strategies adopted to address these issues will be discussed.     

Evaluation of an alcohol-based surgical hand disinfectant containing a synergistic combination of farnesol and benzethonium chloride for immediate and persistent activity against resident hand flora of volunteers and with a novel in vitro pig skin model.

OBJECTIVE: To evaluate the immediate, persistent and sustained in vivo activity of an alcohol-based surgical hand disinfectant, consisting of a zinc gel and a preservative system containing a synergistic combination of farnesol and benzethonium chloride (ZBF disinfectant), and to develop a pig skin model for in vitro evaluation of the immediate and persistent efficacy of alcohol-based surgical hand disinfectants against resident hand flora. DESIGN: The in vivo immediate, persistent, and sustained activity of ZBF disinfectant was evaluated using human volunteers and the "glove-juice" method described in the US Food and Drug Administration's Tentative Final Monograph (FDA-TFM) for Healthcare Antiseptic Products. A novel in vitro pig skin model was developed to compare the immediate and persistent activity of alcohol-based surgical hand disinfectants against resident flora using Staphylococcus epidermidis as the test organism. Four alcohol-based surgical hand disinfectants were evaluated using this model. RESULTS: The results for the ZBF disinfectant exceed the FDA-TFM criteria for immediate, persistent, and sustained activity required for surgical hand disinfectants. The reduction factors for the 4 hand disinfectants obtained using the pig skin model show good agreement with the log(10) reductions in concentrations of hand flora obtained using human volunteers to test for immediate and persistent activity. CONCLUSION: The ZBF disinfectant we evaluated met the FDA-TFM criteria for surgical hand disinfectants. The immediate and persistent efficacy of the surgical hand disinfectants evaluated with the novel pig skin model described in this study shows good agreement with the results obtained in vivo.     

Dermal absorption of isopropyl alcohol from a commercial hand rub: implications for its use in hand decontamination

Isopropyl alcohol-containing hand rubs are widely used in healthcare for hand decontamination. Ten healthy adult volunteers applied a commercially available isopropyl alcohol-containing hand rub to their hands every 10 min over a 4 h period. Blood isopropyl alcohol levels were measured at the beginning and end of the study. At the end of the study, measurable blood isopropyl alcohol levels (range 0.5-1.8 mg/l) were recorded in nine subjects. We confirmed that isopropyl alcohol could be absorbed through the intact skin of adult humans. The social and medical implications are discussed.     

Surgical hand disinfection with a propanol-based hand rub: equivalence of shorter application times

The aim of this study was to determine the efficacy of a propanol-based hand rub at application times shorter than 3 min. The bacterial pre-value was obtained from the finger tips (prEN 12791). Subjects treated their hands with the reference procedure (n-propanol, 60%) for 3 min or the product (crossover design). Sterillium was applied for 3, 2, 1.5 and 1 min. Four other preparations were tested for 1 min. Post-values (immediate effect) were taken from one hand, and the other hand was gloved for 3h. After the gloves were removed, the second post-value was taken (sustained effect). Sterillium was more effective than the reference procedure at 3, 2 and 1.5 min (immediate and sustained effect). The immediate effect after 1 min was significantly lower [mean log(10) reduction factor (RF): 1.91+/-0.90 vs. 2.52+/-0.95; P=0.001], whereas the sustained effect was not (mean RF: 1.81+/-1.06 vs. 2.05+/-1.14; P=0.204). All other preparations failed the efficacy requirement at 1 min for both the immediate and sustained effect. Using 2 x 3 mL Sterillium for a total of 1.5 min for surgical hand disinfection was at least as effective as the 3-min reference disinfection.     

Use of an alcohol-based hand rub and quality improvement interventions to improve hand hygiene in a Russian neonatal intensive care unit.

BACKGROUND: Hand hygiene (HH) is critical to infection control, but compliance is low. Alcohol-based antiseptics may improve HH. HH practices in Russia are not well described, and facilities are often inadequate. SETTING: Four 6-bed units in a neonatal intensive care unit in St. Petersburg, Russia. METHODS: Prospective surveillance of HH compliance, nosocomial colonization, and antibiotic administration was performed from January until June 2000. In February 2000, alcohol-based hand rub was provided for routine HH use. Eight weeks later, a quality improvement intervention was implemented, consisting of review of interim data, identification of opinion leaders, posting of colonization incidence rates, and regular feedback. Means of compliance, colonization, and antibiotic use were compared for periods before and after each intervention. RESULTS: A total of 1,027 events requiring HH were observed. Compliance was 44.2% before the first intervention, 42.3% between interventions, and 48% after the second intervention. Use of alcohol rose from 15.2% of HH indications to 25.2% between interventions and 41.5% after the second intervention. The incidence of nosocomial colonization (per 1,000 patient-days) with Klebsiella pneumoniae was initially 21.5, decreased to 4.7, and then was 3.2 in the final period. Rates of antibiotic and device use also decreased. CONCLUSIONS: HH may have increased slightly, but the largest effect was a switch from soap and water to alcohol which may have been associated with decreased cross-transmission of Klebsiella, although this may have been confounded by lower device use. Alcohol-based antiseptic may be an improvement over current practices, but further research is required.     

Failure of hand disinfection with frequent hand washing: a need for prolonged field studies

In a prolonged field trial a 4% chlorhexidine digluconate detergent scrub (Hibiscrub^R), that had earlier proved to be an effective hand disinfectant, was studied in hospital wards. Finger tips were found to harbour more bacteria than the hand dorsum and the samples collected from them yielded more information on the bacteriological and dermatological effects of hand disinfectants in practice.     

Protection mechanism of probiotic combination against human pathogens: in vitro adhesion to human intestinal mucus

In this study we evaluated the ability of commercial strains (L. rhamnosus GG, L. rhamnosus LC705, and P. freudenreichii ssp. shermanii JS) in combination with B. breve 99 or B. lactis Bb12 to inhibit, displace and compete with model pathogens in order to test their influence on the adhesion of selected pathogens to immobilized human intestinal mucus. Our results demonstrate that specific probiotic combinations are able to enhance the inhibition percentages of pathogens adhesion to intestinal mucus when compared to individual strains. This suggests that combinations of probiotic strains are useful and more effective in inhibition of pathogen adhesion than individual strains. Such combinations should be assessed in clinical studies in subjects where the intestinal microbiota aberrancies have been identified.     

Establishment of a national surveillance system for alcohol-based hand rub consumption and change in consumption over 4 years

Germany established a national surveillance system for alcohol-based hand rub consumption (AHC) in 2008. In 2010, the median AHC was 83 mL/patient-day in 543 intensive care units (ICUs) and 18 mL/patient-day in 4,638 non-ICUs. There was a median increase in AHC of 35.9% (P < .01) in 159 hospitals that participated in the surveillance system for 4 years.     

Antimicrobial activity of home disinfectants and natural products against potential human pathogens.

OBJECTIVE: To assess the efficacy of both natural products (vinegar, baking soda) and common commercial disinfectants (Vesphene IIse, TBQ, Clorox, Lysol Disinfectant Spray, Lysol Antibacterial Kitchen Cleaner, Mr. Clean Ultra, ethanol) designed for home or institutional use against potential human pathogens, including selected antibiotic-resistant bacteria. DESIGN: A quantitative suspension test was used to assess the efficacy of selected disinfectants following exposure times of 30 seconds and 5 minutes. Activity was assessed against Staphylococcus aureus, Salmonella choleraesuis, Escherichia coli O157:H7, and Pseudomonas aeruginosa. Selected disinfectants were also tested against poliovirus, vancomycin-susceptible and -resistant Enterococcus species, and methicillin-susceptible and -resistant S. aureus. RESULTS: The following compounds demonstrated excellent antimicrobial activity (>5.6-8.2 log10 reduction) at both exposure times: TBQ, Vesphene, Clorox, ethanol, and Lysol Antibacterial Kitchen Cleaner. Mr. Clean eliminated 4 to >6 logs10 and Lysol Disinfectant approximately 4 logs10 of pathogenic microorganisms at both exposure times. Vinegar eliminated <3 logs10 of S. aureus and E. coli, and baking soda <3 logs10 of all test pathogens. All tested chemical disinfectants completely inactivated both antibiotic-resistant and -susceptible bacteria at both exposure times. Only two disinfectants, Clorox and Lysol, demonstrated excellent activity (>3 log10 reduction) against poliovirus. CONCLUSIONS: A variety of commercial household disinfectants were highly effective against potential bacterial pathogens. The natural products were less effective than commercial household disinfectants. Only Clorox and Lysol disinfectant were effective against poliovirus.     

一种速干手消毒剂使用效期及消毒效果观察

目的了解速干手消毒剂启用后的有效期,为临床合理使用速干手消毒剂提供参考依据。方法选取某院手卫生依从性排名后4位的临床科室同一时间开启使用的20瓶某品牌速干手消毒剂为研究对象,开启使用后第1天采样,每10 d重复采样直至消毒剂使用完为止。同时对使用相应消毒剂消毒的手采样。检测消毒剂和手标本合格情况。结果共采集消毒剂样本98份,经肉眼观察,整个研究期间20瓶速干手消毒剂无变色、沉淀、悬浮物等。速干手消毒剂开瓶后60 d内检测合格率均为100%。共采集消毒后手标本44份,其中有3份标本检测不合格,均为使用开启后第50天的速干手消毒剂,检测不合格人员使用同批次速干手消毒剂后进行二次采样,检测合格,考虑不合格原因非消毒剂本身影响。结论含醇速干手消毒剂在开启后第60 d仍具有良好的杀菌作用。     

Double-blind, randomized, crossover trial of 3 hand rub formulations: fast-track evaluation of tolerability and acceptability.

OBJECTIVE: To compare healthcare workers' skin tolerance for and acceptance of 3 alcohol-based hand rub formulations. DESIGN: Double-blind, randomized, crossover clinical trial. SETTING: Intensive care unit in a university hospital. PARTICIPANTS: Thirty-eight healthcare workers (HCWs). INTERVENTION: A total of 3 alcohol-based hand rub formulations (hereafter, formulations A, B, and C) were used in random order for 3-5 consecutive working days during regular nursing shifts. Formulations A and B contained the same emollient, and formulations B and C contained the same alcohol at the same concentration. Use of each test formulation was separated by a "washout" period of at least 2 days. A visual assessment of skin integrity by a blinded observer using a standard 6-item scale was conducted before and after the use of each formulation. Univariate and multivariate analyses were used for the assessment of risk factors for skin alteration, and product acceptability was assessed by use of a customized questionnaire after the use of each formulation. RESULTS: Thirty-eight HCWs used each of 3 formulations for a median of 3 days (range, 3-5 days). The mean amount of product used daily (+/-SD) was 54.9+/-23.5 mL (median, 50.9 mL). Both subjective and objective evaluation of skin conditions after use showed lower HCW tolerance for product C. Male sex (odds ratio [OR], 3.17 [95% confidence interval {CI}, 1.1-8.8]), fair or very fair skin (OR, 3.01 [95% CI, 1.1-7.9]), skin alteration before hand rub use (OR, 3.73 [95% CI, 1.7-8.1]), and use of formulation C (OR, 8.79 [95% CI, 2.7-28.4]) were independently associated with skin alteration. CONCLUSIONS: This protocol permits a fast-track comparison of HCWs' skin tolerance for different alcohol-based hand rub formulations that are used in healthcare settings. The emollient in formulation C may account for its inferior performance.     

Adoption of alcohol hand disinfection in the United States: a personal perspective

Even though alcohol-based hand disinfectants have been used for decades as a routine measure in Europe, in the USA until recently handwashing was the procedure of choice. Alcohol-based rub products were recommended only if no handwashing facility or running water was available. It was only during the late 80s and early 90s that the advantages of alcohol-based products began to elicit interest. In 1995 Larsen published new application guidelines for hand disinfection and in 1996 the CDC included alcohol-based hand disinfection in its “Isolation guideline”. However, these recommendations were rarely implemented in practice. In 1996 Didier Pittet first gave me a demonstration of alcohol-based rub products at his Geneva hospital, and the following year experts at Lausanne University provided me with the products available at that time. In 1998 and 2000 I had the opportunity to exchange information and experiences with numerous European experts, including Dr. Molitor, who also gave me additional insights into the mechanism of action of such products. As a result of myriad scientific demonstrations, interest in these rub products now began to be expressed in the USA too. In 1999 an interdisciplinary working group for hand hygiene was set up, comprising representatives from CDC’s Healthcare Infection Control Practices Advisory Committee (HICPAC), the Society for Healthcare Epidemiology of America, the Association for Professionals in Infection Control and the Infectious Diseases Society of America, whose intention was to formulate new guidelines for hand hygiene in the healthcare sector. The insights that I gained from Dr. Molitor and from other European experts were of enormous value and helped to weigh up the pros and cons of alcohol-based hand disinfection, both in respect of the different products available and on comparing them with hand washing. The new CDC guideline for hand hygiene was published in 20002 and for the first time in the USA it featured the requirement that alcohol-based rub products be used as the method of choice provided that the hands were not visibly soiled or contaminated with protein-based material. Unfortunately, we have no reliable data, but it is estimated that today up to 95% of doctors and nurses in American hospitals preferentially use alcohol-based rub products – thus reflecting a situation that has long been common practice in Europe.