- Email: [email protected]
Lack of antimicrobial efficacy of mecetronium etilsulfate in propanol-based hand rubs for surgical hand disinfection
Accepted Manuscript Lack of antimicrobial efficacy of mecetronium etilsulfate in propanol-based hand rubs for surgical hand disinfection Günter Kampf PII:
S0195-6701(17)30122-6
DOI:
10.1016/j.jhin.2017.03.001
Reference:
YJHIN 5045
To appear in:
Journal of Hospital Infection
Received Date: 8 February 2017 Accepted Date: 1 March 2017
Please cite this article as: Kampf G, Lack of antimicrobial efficacy of mecetronium etilsulfate in propanolbased hand rubs for surgical hand disinfection, Journal of Hospital Infection (2017), doi: 10.1016/ j.jhin.2017.03.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Lack of antimicrobial efficacy of mecetronium etilsulfate in propanol-based hand rubs for surgical hand disinfection
Günter Kampf1,2*
1Knieler
und Team GmbH, Infection Control Science, Kattrepelsbrücke 1, 20095 Hamburg,
RI PT
Germany
for Hygiene and Environmental Medicine, University Medicine Greifswald, WalterRathenau-Straße 49 A, 17475 Greifswald, Germany; email: [email protected]
AC C
EP
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M AN U
SC
2Institute
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ACCEPTED MANUSCRIPT Summary
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M AN U
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The aim of the study was to determine if mecetronium etilsulfate (MES) contributes to the overall efficacy in surgical hand disinfection using, for the first time, ideal controls. Three blinded hand rubs (45% iso-propanol, 30% n-propanol) were applied for 1.5 min and compared with the EN 12791 reference procedure (cross-over design). One commercial hand rub contained 0.2% MES, the two other rubs were identical apart from 0.2% MES. None of the formulations revealed a log10-reduction after 3 h which was significantly better compared to the reference procedure (1.72 ± 1.15). The antimicrobial contribution of MES in hand rubs is questionable.
Page 2
ACCEPTED MANUSCRIPT Introduction
SC
RI PT
Various hand rubs used in Europe, the middle East and India contain in addition to 45% (w/w) iso-propanol and 30% (w/w) n-propanol a substance named mecetronium etilsulfate (MES; CAS number: 3006-10-8) in a concentration of 0.2% (w/w). It is a detergent and belongs to the group of surface-active ingredients. Its aim in hand rubs is to contribute to the overall antimicrobial efficacy. The effect of a non-volatile substance may be reasonable in surgical hand disinfection in order to slow down the recolonization of the resident hand flora under the surgical glove. This effect may help to reduce the microbial load in the glove juice which may enter the surgical site in case of glove perforations. In EN 12791 this type of effect is called “sustained efficacy” 1. So far, however, there is no direct evidence that MES significantly contributes in identical formulations to the overall efficacy in surgical hand disinfection. The aim of the study was therefore to find out if the addition of 0.2% MES to a propanol-based hand rub yields a superior antimicrobial effect after 3 h in surgical hand disinfection. Material and methods
M AN U
Test principle of EN 12791
EN 12791 describes a design that allows measuring the efficacy of hand rubs in comparison to the reference procedure (application of n-propanol at 60% v/v for 3 min). A hand rub is considered to be effective if the mean log10-reduction is non-inferior in comparison to the reference procedure after 0 h (immediate effect) and 3 h under the surgical glove. A hand rub may reveal a sustained efficacy if the mean log10-reduction after 3 h is superior in comparison to the reference procedure.
TE D
Test products
Three hand rubs were used, all based on 45% (w/w) iso-propanol and 30% (w/w) n-propanol: hand rub 1 (commercially available); hand rub 2 (identical formulation as hand rub 1 but supplemented with 0.2% MES); hand rub 3 (commercially available) which contains 0.2% MES classified as “active ingredient”.
EP
• • •
AC C
All hand rubs contain two similar emollients. As described in EN 12791, n-propanol at 60% (v/v) served as the reference alcohol and was coded in this study as hand rub 4. All formulations were blinded until the statistical evaluation was finished. Surgical hand disinfection procedure All experiments were performed between June and August 2015 at Dr. Brill + Partner GmbH, Institut für Hygiene und Mikrobiologie, Hamburg, Germany. 25 healthy volunteers were recruited; 23 of them completed all study arms. The four treatments were randomized in a crossover Latin-square design 1. No skin breaks, such as cuts or abrasions, and no other skin disorders were present. Nails were short and clean. Volunteers did not use any substances with antibacterial activity or antibacterial soaps for one week prior to testing. A rest period of at least one week elapsed between each product application in order to allow the reconstitution of normal skin flora.
Page 3
ACCEPTED MANUSCRIPT Volunteers’ hands were washed with five ml of a non-medicated soap (sapo kalinus) and rubbed vigorously on to the skin up to the wrists for 1 min. Hands were then rinsed with running tap water and dried with a sterile paper towel.
RI PT
Fingertips of both hands were rubbed separately for 1 min on to two Petri dishes containing 10 ml of tryptic soy broth (TSB). From the sampling fluid obtained from each hand, a 0.1 ml aliquot, as well as 0.1 mL of 1:10 and 1:100 dilutions, were seeded in TSB. Sampling fluids were spread over tryptic soy agar (TSA) dishes with a sterile glass spatula. Dishes were incubated for a total of 48 h at 36°C ± 1°C and the colony forming units (cfu) were counted.
M AN U
SC
For the disinfection step each volunteer applied as many portions of 3 ml as necessary to keep both hands wet for the corresponding application time: 1.5 min for each of the three hand rubs, and 3 min for the reference alcohol. The six step rub-in technique was applied as described in EN 12791. After the disinfection step, the volunteer rubbed the fingertips of one hand (selected at random) for 1 min on to a Petri dish containing 10 ml of TSB supplemented with neutralizers (immediate effect). The following neutralizers were used: 3.0 % Tween 80, 3.0 % saponin, 0.1% lecithin and 0.1% histidine. Their suitability was validated for each formulation using Staphylococcus aureus, Enterococcus hirae, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. This validation ensures that common and different microorganisms possibly found on previously untreated hands are no longer inactivated by residuals of the hand rubs after contact with the neutralizer broth. The other hand was gloved for 3 h for assessment of the 3 h effect. After removing the glove, sampling was done in the same way as for the immediate effect. From the sampling fluid, both 1 and 0.1 ml aliquots were seeded in Petri dishes with solidified TSA. A 1:10 dilution of the sampling fluid in TSB was prepared and a 0.1-ml aliquot was seeded as above. Dishes were incubated at 36°C ± 1°C for a total of 48 h. Calculation of efficacy
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For each dilution, the mean number of cfu was calculated. The mean number was then multiplied by the dilution factor in order to obtain the number of cfu/ml of sampling liquid. All pre- and post-values were expressed as log10 values. For calculation purposes, values of 0 (log 0 = -∞) were reset to 1 (log 1 = 0). For each volunteer, the logarithmic reduction was obtained as the difference between the log10 pre-value and the log10 post-values. The mean of the reference treatment was compared with the corresponding mean for each product for a paired analysis of the immediate and 3 h effects. For a product to be considered effective for surgical disinfection, the mean log10-reduction of both the immediate and 3 h effects had to be not significantly lower than the corresponding mean of the 3-min reference treatment. Statistical evaluation
In order to compare the mean log10-reduction between all four treatments, an analysis of variance was performed. The Wilcoxon matched-pairs signed-ranks test was performed for testing for superiority of a hand rub in comparison to the reference treatment after 3 h (“sustained effect”). For both test PSPP was used (GNU project, free software foundation). Results The efficacy of the three hand rubs for surgical hand disinfection is summarized in Table I, described as the mean log10-reduction of hand flora. The strongest immediate effect with a mean log10-reduction of 1.75 was found with hand rub 1, the strongest 3 h effect with a mean log10-reduction of 1.83 showed hand rub 2. There was, however, no significant difference between any of the four treatments in both the immediate Page 4
ACCEPTED MANUSCRIPT effect (p = 0.947; ANOVA) and the 3 h effect (p = 0.945). An additional analysis revealed that the 3 h effect of all three hand rubs was not superior to the reference treatment (Table I). Discussion
RI PT
Based on our data 0.2% MES in 45% iso-propanol and 30% n-propanol (both w/w) applied for 1.5 min with a mean hand rub volume of 6.13 ± 0.95 ml does not exhibit a measurable antimicrobial effect after 3 h in surgical hand disinfection. Various studies on the efficacy of propanol-based formulations with 0.2% MES applied for 1.5 min (as recommended) are published, and the efficacy compared to the 3 min reference procedure of EN 12791 2. None of the 14 data sets from published studies revealed an efficacy of the MES-containing hand rubs after 3 h which was superior to the reference procedure 2. It is therefore more than doubtful if MES at 0.2% indeed contributes in a measurable way to the overall antimicrobial efficacy.
M AN U
SC
It is considered vitally important to maintain the lowest possible contamination of the surgical field, especially in the event of sterile glove puncture during surgery. The WHO hand hygiene guidelines from 2009 recommend preferably using “a product ensuring sustained activity” 3. It was assumed that the sustained activity ensured by certain products (for example, CHG) was desirable, but there was no evidence that these products were more effective in directly reducing the risk of surgical site infection. In the absence of such evidence on surgical site infection, the WHO guideline development group decided not to make any recommendations on specific products with or without a sustained effect 3. It emphasized, however, the need to define what is considered a “suitable” product 3. Based on the presented data, it may well be an alcoholbased formulation without 0.2% MES in terms of antimicrobial efficacy.
EP
TE D
MES is a detergent which has on the one hand been shown to have a certain skin smoothing effect 4. WHO recommends using hand rub with a low irritancy potential. That is why for healthcare workers the irritation potential of MES is probably more relevant. MES has also been described to have a weak irritancy effect. A propanol-based hand rub with 0.2% MES and emollients showed in a patch test a significantly higher transepidermal water loss (TEWL) compared to the application of the same two alcohols without MES and without emollients 5. Even the emollients could not compensate for the small but measurable irritating effect of MES although non-comparative data for commonly used hand rubs with 0.2% MES indicate an overall good dermal tolerance 6.
AC C
MES belongs to the group of surface-active ingredients. A recent survey found out that in Germany the majority of surface-active ingredients coming into the environment from hand and skin disinfection products in healthcare is MES with approximately 89% resulting in a mean exposure of 0.032 g per hospital bed and day 7. In 2013, a total of 500,671 hospital beds were available in Germany. The annual MES exposure in Germany from hospitals alone by hand and skin disinfectants would sum up to 5847.8 kg. Use of the same products in medical practice, ambulant nursing services, nursing homes and anywhere via pharmacy sale will substantially add to this amount. Most of it will be found sooner or later in the environment, probably in the aquatic environment when hands are washed and MES is rinsed off from previous hand disinfections. Prevention of environmental contamination with antimicrobials is one element to limit the spread of antimicrobial-resistant microbes 8. In order to preserve effective biocidal products for the prevention of transmission of nosocomial pathogens it is therefore essential to restrict the use and thereby the overall environmental load to those substances having a clear scientific benefit. MES appears to be dispensable in that respect. In the last decade hand rubs were preferred when they did not contain any fragrance or dye because there was a very small risk associated with its use but no benefit resulting in an overall Page 5
ACCEPTED MANUSCRIPT negative risk-benefit-assessment for both types of ingredient 9. It is now time to review the use of non-volatile “active” ingredients in hand rubs with the goal to evaluate if any benefit truly outweighs the associated risks 10. It may be time to take a conscious decision to prefer (if available) hand rubs with the same efficacy, dermal tolerance und user acceptability but without abdicable non-volatile “active” substances. Conclusions
RI PT
MES at 0.2% in a propanol-based hand rub does not significantly improve efficacy in surgical hand disinfection after 3 h under the surgical glove when used as recommended. Conflict of interest
SC
The study was funded by Lohmann & Rauscher International GmbH & Co. KG, Rengsdorf, Germany. The sponsor had no influence on study design, the collection, analysis and interpretation of data and the manuscript content. References
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1. EN 12791:2015. Chemical disinfectants and antiseptics. Surgical hand disinfection. Test method and requirement (phase 2, step 2). Brussels: CEN - Comité Européen de Normalisation; 2015. 2. Kampf G, Kramer A, Suchomel M. Lack of sustained efficacy for alcohol-based surgical hand rubs containing “residual active ingredients” according to EN 12791. Journal of Hospital Infection 2017; 95: in press. 3. WHO. Global guidelines for the prevention of surgical site infections. Geneva: WHO; 2016. 4. Proske O, Sauermann G, Pietsch H, Rohde B. Die Hautverträglichkeit von Mecetroniumetilsulfat in einem Desinfektionsmittel - eine klinische Studie. Hygiene + Medizin 1995; 20: 535-42. 5. Slotosch CM, Kampf G, Löffler H. Effects of disinfectants and detergents on skin irritation. Contact Dermatitis 2007; 57: 235-41. 6. Kampf G, Wigger-Alberti W, Wilhelm KP. Do atopics tolerate alcohol-based hand rubs? A prospective, controlled, randomized double-blind clinical trial. Acta dermato-venereologica 2006; 86(2): 140-3. 7. Tluczkiewicz I, Bitsch A, Hahn S, Hahn T. Emission of biocides from hospitals: comparing current survey results with European Union default values. Integrated environmental assessment and management 2010; 6(2): 273-80. 8. Holmes AH, Moore LS, Sundsfjord A, et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016; 387(10014): 176-87. 9. Aktion Saubere Hände. http://wwwaktionsauberehaendede/fileadmin/ash/downloads/pdf/ASH_Positionspapier_Hautschutz_Hautpflege_FarbParuemfrei_112010pdf 2010. 10. Kampf G. Acquired resistance to chlorhexidine – is it time to establish an “antiseptic stewardship” initiative? Journal of Hospital Infection 2016; 94(3): 213-27.
Page 6
ACCEPTED MANUSCRIPT Table I: Efficacy of three hand rubs based on 45% iso-propanol and 30% n-propanol (both w/w) according to EN 12791; only hand rubs 2 and 3 contain 0.2% MES; *Wilcoxon matched-pairs signed-ranks test for superiority to the reference treatment (3 h effect); n.a. = not applicable. Parameter
Reference alcohol 3 min 5.74 ± 1.25 ml 1.62 ± 1.24 1.72 ± 1.15 n.a.
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Mean log10-reduction with stdev Hand rub 1 Hand rub 2 Hand rub 3 Application time 1.5 min 1.5 min 1.5 min Mean applied volume 6.26 ± 0.86 6.26 ± 0.86 5.87 ± 1.10 ml ml ml 0 h effect 1.75 ± 0.87 1.59 ± 1.03 1.70 ± 0.82 3 h effect 1.67 ± 1.12 1.83 ± 1.31 1.62 ± 1.24 p-value* n.a. 0.503 n.a.
Page 7
S0195-6701(17)30122-6
DOI:
10.1016/j.jhin.2017.03.001
Reference:
YJHIN 5045
To appear in:
Journal of Hospital Infection
Received Date: 8 February 2017 Accepted Date: 1 March 2017
Please cite this article as: Kampf G, Lack of antimicrobial efficacy of mecetronium etilsulfate in propanolbased hand rubs for surgical hand disinfection, Journal of Hospital Infection (2017), doi: 10.1016/ j.jhin.2017.03.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Lack of antimicrobial efficacy of mecetronium etilsulfate in propanol-based hand rubs for surgical hand disinfection
Günter Kampf1,2*
1Knieler
und Team GmbH, Infection Control Science, Kattrepelsbrücke 1, 20095 Hamburg,
RI PT
Germany
for Hygiene and Environmental Medicine, University Medicine Greifswald, WalterRathenau-Straße 49 A, 17475 Greifswald, Germany; email: [email protected]
AC C
EP
TE D
M AN U
SC
2Institute
Page 1
ACCEPTED MANUSCRIPT Summary
AC C
EP
TE D
M AN U
SC
RI PT
The aim of the study was to determine if mecetronium etilsulfate (MES) contributes to the overall efficacy in surgical hand disinfection using, for the first time, ideal controls. Three blinded hand rubs (45% iso-propanol, 30% n-propanol) were applied for 1.5 min and compared with the EN 12791 reference procedure (cross-over design). One commercial hand rub contained 0.2% MES, the two other rubs were identical apart from 0.2% MES. None of the formulations revealed a log10-reduction after 3 h which was significantly better compared to the reference procedure (1.72 ± 1.15). The antimicrobial contribution of MES in hand rubs is questionable.
Page 2
ACCEPTED MANUSCRIPT Introduction
SC
RI PT
Various hand rubs used in Europe, the middle East and India contain in addition to 45% (w/w) iso-propanol and 30% (w/w) n-propanol a substance named mecetronium etilsulfate (MES; CAS number: 3006-10-8) in a concentration of 0.2% (w/w). It is a detergent and belongs to the group of surface-active ingredients. Its aim in hand rubs is to contribute to the overall antimicrobial efficacy. The effect of a non-volatile substance may be reasonable in surgical hand disinfection in order to slow down the recolonization of the resident hand flora under the surgical glove. This effect may help to reduce the microbial load in the glove juice which may enter the surgical site in case of glove perforations. In EN 12791 this type of effect is called “sustained efficacy” 1. So far, however, there is no direct evidence that MES significantly contributes in identical formulations to the overall efficacy in surgical hand disinfection. The aim of the study was therefore to find out if the addition of 0.2% MES to a propanol-based hand rub yields a superior antimicrobial effect after 3 h in surgical hand disinfection. Material and methods
M AN U
Test principle of EN 12791
EN 12791 describes a design that allows measuring the efficacy of hand rubs in comparison to the reference procedure (application of n-propanol at 60% v/v for 3 min). A hand rub is considered to be effective if the mean log10-reduction is non-inferior in comparison to the reference procedure after 0 h (immediate effect) and 3 h under the surgical glove. A hand rub may reveal a sustained efficacy if the mean log10-reduction after 3 h is superior in comparison to the reference procedure.
TE D
Test products
Three hand rubs were used, all based on 45% (w/w) iso-propanol and 30% (w/w) n-propanol: hand rub 1 (commercially available); hand rub 2 (identical formulation as hand rub 1 but supplemented with 0.2% MES); hand rub 3 (commercially available) which contains 0.2% MES classified as “active ingredient”.
EP
• • •
AC C
All hand rubs contain two similar emollients. As described in EN 12791, n-propanol at 60% (v/v) served as the reference alcohol and was coded in this study as hand rub 4. All formulations were blinded until the statistical evaluation was finished. Surgical hand disinfection procedure All experiments were performed between June and August 2015 at Dr. Brill + Partner GmbH, Institut für Hygiene und Mikrobiologie, Hamburg, Germany. 25 healthy volunteers were recruited; 23 of them completed all study arms. The four treatments were randomized in a crossover Latin-square design 1. No skin breaks, such as cuts or abrasions, and no other skin disorders were present. Nails were short and clean. Volunteers did not use any substances with antibacterial activity or antibacterial soaps for one week prior to testing. A rest period of at least one week elapsed between each product application in order to allow the reconstitution of normal skin flora.
Page 3
ACCEPTED MANUSCRIPT Volunteers’ hands were washed with five ml of a non-medicated soap (sapo kalinus) and rubbed vigorously on to the skin up to the wrists for 1 min. Hands were then rinsed with running tap water and dried with a sterile paper towel.
RI PT
Fingertips of both hands were rubbed separately for 1 min on to two Petri dishes containing 10 ml of tryptic soy broth (TSB). From the sampling fluid obtained from each hand, a 0.1 ml aliquot, as well as 0.1 mL of 1:10 and 1:100 dilutions, were seeded in TSB. Sampling fluids were spread over tryptic soy agar (TSA) dishes with a sterile glass spatula. Dishes were incubated for a total of 48 h at 36°C ± 1°C and the colony forming units (cfu) were counted.
M AN U
SC
For the disinfection step each volunteer applied as many portions of 3 ml as necessary to keep both hands wet for the corresponding application time: 1.5 min for each of the three hand rubs, and 3 min for the reference alcohol. The six step rub-in technique was applied as described in EN 12791. After the disinfection step, the volunteer rubbed the fingertips of one hand (selected at random) for 1 min on to a Petri dish containing 10 ml of TSB supplemented with neutralizers (immediate effect). The following neutralizers were used: 3.0 % Tween 80, 3.0 % saponin, 0.1% lecithin and 0.1% histidine. Their suitability was validated for each formulation using Staphylococcus aureus, Enterococcus hirae, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. This validation ensures that common and different microorganisms possibly found on previously untreated hands are no longer inactivated by residuals of the hand rubs after contact with the neutralizer broth. The other hand was gloved for 3 h for assessment of the 3 h effect. After removing the glove, sampling was done in the same way as for the immediate effect. From the sampling fluid, both 1 and 0.1 ml aliquots were seeded in Petri dishes with solidified TSA. A 1:10 dilution of the sampling fluid in TSB was prepared and a 0.1-ml aliquot was seeded as above. Dishes were incubated at 36°C ± 1°C for a total of 48 h. Calculation of efficacy
AC C
EP
TE D
For each dilution, the mean number of cfu was calculated. The mean number was then multiplied by the dilution factor in order to obtain the number of cfu/ml of sampling liquid. All pre- and post-values were expressed as log10 values. For calculation purposes, values of 0 (log 0 = -∞) were reset to 1 (log 1 = 0). For each volunteer, the logarithmic reduction was obtained as the difference between the log10 pre-value and the log10 post-values. The mean of the reference treatment was compared with the corresponding mean for each product for a paired analysis of the immediate and 3 h effects. For a product to be considered effective for surgical disinfection, the mean log10-reduction of both the immediate and 3 h effects had to be not significantly lower than the corresponding mean of the 3-min reference treatment. Statistical evaluation
In order to compare the mean log10-reduction between all four treatments, an analysis of variance was performed. The Wilcoxon matched-pairs signed-ranks test was performed for testing for superiority of a hand rub in comparison to the reference treatment after 3 h (“sustained effect”). For both test PSPP was used (GNU project, free software foundation). Results The efficacy of the three hand rubs for surgical hand disinfection is summarized in Table I, described as the mean log10-reduction of hand flora. The strongest immediate effect with a mean log10-reduction of 1.75 was found with hand rub 1, the strongest 3 h effect with a mean log10-reduction of 1.83 showed hand rub 2. There was, however, no significant difference between any of the four treatments in both the immediate Page 4
ACCEPTED MANUSCRIPT effect (p = 0.947; ANOVA) and the 3 h effect (p = 0.945). An additional analysis revealed that the 3 h effect of all three hand rubs was not superior to the reference treatment (Table I). Discussion
RI PT
Based on our data 0.2% MES in 45% iso-propanol and 30% n-propanol (both w/w) applied for 1.5 min with a mean hand rub volume of 6.13 ± 0.95 ml does not exhibit a measurable antimicrobial effect after 3 h in surgical hand disinfection. Various studies on the efficacy of propanol-based formulations with 0.2% MES applied for 1.5 min (as recommended) are published, and the efficacy compared to the 3 min reference procedure of EN 12791 2. None of the 14 data sets from published studies revealed an efficacy of the MES-containing hand rubs after 3 h which was superior to the reference procedure 2. It is therefore more than doubtful if MES at 0.2% indeed contributes in a measurable way to the overall antimicrobial efficacy.
M AN U
SC
It is considered vitally important to maintain the lowest possible contamination of the surgical field, especially in the event of sterile glove puncture during surgery. The WHO hand hygiene guidelines from 2009 recommend preferably using “a product ensuring sustained activity” 3. It was assumed that the sustained activity ensured by certain products (for example, CHG) was desirable, but there was no evidence that these products were more effective in directly reducing the risk of surgical site infection. In the absence of such evidence on surgical site infection, the WHO guideline development group decided not to make any recommendations on specific products with or without a sustained effect 3. It emphasized, however, the need to define what is considered a “suitable” product 3. Based on the presented data, it may well be an alcoholbased formulation without 0.2% MES in terms of antimicrobial efficacy.
EP
TE D
MES is a detergent which has on the one hand been shown to have a certain skin smoothing effect 4. WHO recommends using hand rub with a low irritancy potential. That is why for healthcare workers the irritation potential of MES is probably more relevant. MES has also been described to have a weak irritancy effect. A propanol-based hand rub with 0.2% MES and emollients showed in a patch test a significantly higher transepidermal water loss (TEWL) compared to the application of the same two alcohols without MES and without emollients 5. Even the emollients could not compensate for the small but measurable irritating effect of MES although non-comparative data for commonly used hand rubs with 0.2% MES indicate an overall good dermal tolerance 6.
AC C
MES belongs to the group of surface-active ingredients. A recent survey found out that in Germany the majority of surface-active ingredients coming into the environment from hand and skin disinfection products in healthcare is MES with approximately 89% resulting in a mean exposure of 0.032 g per hospital bed and day 7. In 2013, a total of 500,671 hospital beds were available in Germany. The annual MES exposure in Germany from hospitals alone by hand and skin disinfectants would sum up to 5847.8 kg. Use of the same products in medical practice, ambulant nursing services, nursing homes and anywhere via pharmacy sale will substantially add to this amount. Most of it will be found sooner or later in the environment, probably in the aquatic environment when hands are washed and MES is rinsed off from previous hand disinfections. Prevention of environmental contamination with antimicrobials is one element to limit the spread of antimicrobial-resistant microbes 8. In order to preserve effective biocidal products for the prevention of transmission of nosocomial pathogens it is therefore essential to restrict the use and thereby the overall environmental load to those substances having a clear scientific benefit. MES appears to be dispensable in that respect. In the last decade hand rubs were preferred when they did not contain any fragrance or dye because there was a very small risk associated with its use but no benefit resulting in an overall Page 5
ACCEPTED MANUSCRIPT negative risk-benefit-assessment for both types of ingredient 9. It is now time to review the use of non-volatile “active” ingredients in hand rubs with the goal to evaluate if any benefit truly outweighs the associated risks 10. It may be time to take a conscious decision to prefer (if available) hand rubs with the same efficacy, dermal tolerance und user acceptability but without abdicable non-volatile “active” substances. Conclusions
RI PT
MES at 0.2% in a propanol-based hand rub does not significantly improve efficacy in surgical hand disinfection after 3 h under the surgical glove when used as recommended. Conflict of interest
SC
The study was funded by Lohmann & Rauscher International GmbH & Co. KG, Rengsdorf, Germany. The sponsor had no influence on study design, the collection, analysis and interpretation of data and the manuscript content. References
AC C
EP
TE D
M AN U
1. EN 12791:2015. Chemical disinfectants and antiseptics. Surgical hand disinfection. Test method and requirement (phase 2, step 2). Brussels: CEN - Comité Européen de Normalisation; 2015. 2. Kampf G, Kramer A, Suchomel M. Lack of sustained efficacy for alcohol-based surgical hand rubs containing “residual active ingredients” according to EN 12791. Journal of Hospital Infection 2017; 95: in press. 3. WHO. Global guidelines for the prevention of surgical site infections. Geneva: WHO; 2016. 4. Proske O, Sauermann G, Pietsch H, Rohde B. Die Hautverträglichkeit von Mecetroniumetilsulfat in einem Desinfektionsmittel - eine klinische Studie. Hygiene + Medizin 1995; 20: 535-42. 5. Slotosch CM, Kampf G, Löffler H. Effects of disinfectants and detergents on skin irritation. Contact Dermatitis 2007; 57: 235-41. 6. Kampf G, Wigger-Alberti W, Wilhelm KP. Do atopics tolerate alcohol-based hand rubs? A prospective, controlled, randomized double-blind clinical trial. Acta dermato-venereologica 2006; 86(2): 140-3. 7. Tluczkiewicz I, Bitsch A, Hahn S, Hahn T. Emission of biocides from hospitals: comparing current survey results with European Union default values. Integrated environmental assessment and management 2010; 6(2): 273-80. 8. Holmes AH, Moore LS, Sundsfjord A, et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016; 387(10014): 176-87. 9. Aktion Saubere Hände. http://wwwaktionsauberehaendede/fileadmin/ash/downloads/pdf/ASH_Positionspapier_Hautschutz_Hautpflege_FarbParuemfrei_112010pdf 2010. 10. Kampf G. Acquired resistance to chlorhexidine – is it time to establish an “antiseptic stewardship” initiative? Journal of Hospital Infection 2016; 94(3): 213-27.
Page 6
ACCEPTED MANUSCRIPT Table I: Efficacy of three hand rubs based on 45% iso-propanol and 30% n-propanol (both w/w) according to EN 12791; only hand rubs 2 and 3 contain 0.2% MES; *Wilcoxon matched-pairs signed-ranks test for superiority to the reference treatment (3 h effect); n.a. = not applicable. Parameter
Reference alcohol 3 min 5.74 ± 1.25 ml 1.62 ± 1.24 1.72 ± 1.15 n.a.
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TE D
M AN U
SC
RI PT
Mean log10-reduction with stdev Hand rub 1 Hand rub 2 Hand rub 3 Application time 1.5 min 1.5 min 1.5 min Mean applied volume 6.26 ± 0.86 6.26 ± 0.86 5.87 ± 1.10 ml ml ml 0 h effect 1.75 ± 0.87 1.59 ± 1.03 1.70 ± 0.82 3 h effect 1.67 ± 1.12 1.83 ± 1.31 1.62 ± 1.24 p-value* n.a. 0.503 n.a.
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