1. Journals Overview
    2. GMS Hygiene and Infection Control
    3. Jahrgang 16
    4. Reply to the letter to the editor by R. Papke
journal_logo

GMS Hygiene and Infection Control

Deutsche Gesellschaft für Allgemeine und Krankenhaus-Hygiene (DGKH)

2196-5226


Der Artikel liegt nur in englischer Sprache vor.
Letter to the Editor

Reply to the letter to the editor by R. Papke

 Martin Exner 1
Sanjay Bhattacharya 2
Jürgen Gebel 1
Peter Goroncy-Bermes 3
Philippe Hartemann 4
Peter Heeg 5
Carola Ilschner 1
Axel Kramer 6
Moi Lin Ling 7
Wolfgang Merkens 3
Peter Oltmanns 3
Frank Pitten 8
Manfred Rotter 9
Ricarda Maria Schmithausen 1
Hans-Günther Sonntag 10
Kathrin Steinhauer 3
Matthias Trautmann 11

1 Institute of Hygiene and Public Health, Bonn University, Bonn, Germany
2 Tata Medical Center, Kolkata, India
3 Schülke & Mayr GmbH, Norderstedt, Germany
4 Departement Environnement et Santé Publique S.E.R.E.S., Faculté de Médecine, Nancy, France
5 Institute of Medical Microbiology and Hygiene, University of Tübingen, Germany
6 Institute of Hygiene and Environmental Medicine, University Medicine Greifswald, Germany
7 Infection Prevention & Control, Singapore General Hospital, Singapore
8 IKI - Institut für Krankenhaushygiene & Infektionskontrolle GmbH, Gießen, Germany
9 Hygiene Institute, Medical University Vienna, Austria
10 Institute of Hygiene and Medical Microbiology, University of Heidelberg, Germany
11 Department of Hospital Hygiene, Stuttgart Hospital, Stuttgart, Germany



Authors’ statement

We are grateful for the question by Papke [1] because it addresses an important issue regarding the risk-conscious use of hand disinfectants.

The KRINKO does not recommend adding quaternary ammonium compounds (QAC) to hand disinfectants without mentioning the active ingredient mecetronium ethylsulfate (MES). However, mecetronium ethylsulfate (syn. Ethylhexadecyldimethylammonium-ethylsulfate) is a surface-active aliphatic quaternary ammonium compound, so that this active ingredient is also included in the KRINKO’s disapproval recommendation.

MES was chosen as an example in our publication because it is used in hand disinfectants [2] as well as in shampoos [3], but the reasons against its wide use are little known to the user. In this respect, the question may help to clarify the situation.

The use of MES in hand disinfectants should be avoided for the following reasons:

  • In the results of 23 studies, no improvement in efficacy was achieved by adding 0.2% MES to a propanol-based hand disinfectant, tested according to EN 12791 [4]. The same applies to chlorhexidine digluconate and 2-phenylphenol [4]. Also for surgical hand disinfection, no improvement in efficacy was demonstrated by addition of MES [5].
  • After dermal application under occlusive conditions for 24 h, the percutaneous absorption of MES in the rat was approx. 2% [6]. By extrapolation from dermal toxicity data, the absorption was calculated to be 3% [7].
  • For the quaternary ammonium compounds benzalkonium chloride (BAC) and didecyldimethylammonium chloride (DDAC), blood levels of both compounds were measured for the first time in 2020 in a sample of healthy people, with quaternary ammonium compound (QAC) exposure (n=43) at concentrations with possible impact on cell metabolism in cell culture, reduction of mitochondrial function, and increase of inflammatory cytokines in volunteers in a dose-dependent manner [8]. The reason for the occurrence in humans is the wide use of both QAC in disinfectants and cleaning agents, for the preservation of care products and in food preparation. In surface disinfection, the main exposure to QAC probably occurs by inhalation (aerosol, dust) [9]. Unlike BAC and DDAC, MES is only used as an additive in hand disinfectants and shampoos. However, due to the dermal absorption of MES, a systemic toxic risk cannot be ruled out by daily application for hand disinfection up to >100 times, depending on the work area. Since the addition of MES to hand disinfectants is not associated with any improvement in efficacy, but absorptive toxic risks including unknown summation effects with BAC and DDAC may result, the use of hand disinfectants with the addition of MES should be discouraged in view of the new findings on the toxic hazard of BAC and DDAC, until the safety of the adsorptive uptake of MES has been proven by in-depth studies.
  • A genetically encoded development of resistance with simultaneous increase in resistance to antibiotics has been demonstrated for BAC [10]. When passaged in vitro at subinhibitory concentrations, tolerance is induced by both BAC and DDAC [11], [12], [13], [14]. Although such studies have not been performed with MES, such a risk cannot be ruled out for MES due to the structural similarity, the mode of mechanism and, in particular, the application in a submicrobicidal concentration of 0.2%.

Conclusions

The occurrence of QAC in the blood of healthy people is an alarm signal that exposure to antimicrobial active QAC must be limited to the indispensable minimum. Since the addition of MES to propanol-based hand disinfectants did not improve their efficacy, but the active ingredient is absorbed dermally, the use of hand disinfectants containing MES cannot be recommended until toxic long-term risks and the development of tolerance and resistance have been reliably ruled out.

Notes

Competing interests

The authors declare that they have no competing interests.

References

[1] Papke R. Letter to the Editor regarding “Chemical disinfection in healthcare settings: critical aspects for the development of global strategies”. GMS Hyg Infect Control. 2021;16:Doc22. DOI: 10.3205/dgkh000393
[2] Hartmann. The Sterillium® product range. Available from: https://www.sterillium.info/en/product-range
[3] Plater MJ, Raab A. Liquid chromatography-mass spectrometry analysis of dyes formed by in situ oxidative methods then purified by absorption and extraction from hair wefts. J Chem Res. 2020. DOI: 10.1177/1747519820978621
[4] Kampf G, Suchomel M, Kramer A. Lack of sustained efficacy for alcohol-based surgical hand rubs containing 'residual active ingredients' according to EN 12791. J Hosp Inf. 2017;95: 163-8. DOI: 10.1016/j.jhin.2016.11.001
[5] Kampf G. Lack of antimicrobial efficacy of mecetronium etilsulfate in propanol-based hand rubs for surgical hand disinfection. J Hosp Infect. 2017 Jun;96(2):189-91. DOI: 10.1016/j.jhin.2017.03.001
[6] Widulle P, Kramer A, Reichwagen S, Heldt P. Oberflächenaktive Verbindungen. In: Kramer A, Assadian O, editors. Wallhäußers Praxis der Sterilisation, Desinfektion, Antiseptik und Konservierung. Thieme: Stuttgart; 2008. p. 690-710.
[7] ECHA. Opinion proposing harmonised classification and labelling at EU level of mecetronium etilsulfate; N-ethyl-N,N-dimethylhexadecan-1-aminium ethyl sulfate; Mecetronium ethyl sulphate [MES]. 2018 Sep 14. Available from: https://echa.europa.eu/documents/10162/19c8b515-1ef5-cefe-f7f4-4bf7178338da
[8] Hrubec TC, Seguin RP, Xu L, Cortopassi GA, Datta S, Hanlon AL, Lozano AJ, McDonald VA, Healy CA, Anderson TC, Musse NA, Williams RT. Altered toxicological endpoints in humans from common quaternary ammonium compound disinfectant exposure. Toxicol Rep. 2021 Mar 9;8:646-56. DOI: 10.1016/j.toxrep.2021.03.006
[9] Feld H, Oberender N. Die unkontrollierte Verbreitung von quartären Ammoniumverbindungen (QAV) in Alltagsprodukten sowie in medizinischen und industriellen Bereichen – kritisch für Mensch, Material und Umwelt. Hyg Med. 2018;43(5):D37-D45.
[10] He GX, Landry M, Chen H, Thorpe C, Walsh D, Varela MF, Pan H. Detection of benzalkonium chloride resistance in community environmental isolates of staphylococci. J Med Microbiol. 2014 May;63(Pt 5):735-41. DOI: 10.1099/jmm.0.073072-0
[11] Adair FW, Geftic SG, Gelzer J. Resistance of Pseudomonas to quaternary ammonium compounds. I. Growth in benzalkonium chloride solution. Appl Microbiol. 1969;18(3):299-302. DOI: 10.1128/am.18.3.299-302.1969
[12] Walsh SE, Maillard JY, Russell AD, Catrenich CE, Charbonneau DL, Bartolo RG. Development of bacterial resistance to several biocides and effects on antibiotic susceptibility. J Hosp Infect. 2003 Oct;55(2):98-107. DOI: 10.1016/s0195-6701(03)00240-8
[13] Voumard M, Venturelli L, Borgatta M, Croxatto A, Kasas S, Dietler G, Breider F, von Gunten U. Adaptation of Pseudomonas aeruginosa to constant sub-inhibitory concentrations of quaternary ammonium compounds. Environ Sci Water Res Technol. 2020;6(4):1139-52. DOI: 10.1039/C9EW01056D
[14] Soumet C, Méheust D, Pissavin C, Le Grandois P, Frémaux B, Feurer C, Le Roux A, Denis M, Maris P. Reduced susceptibilities to biocides and resistance to antibiotics in food-associated bacteria following exposure to quaternary ammonium compounds. J Appl Microbiol. 2016 Nov;121(5):1275-81. DOI: 10.1111/jam.13247
[15] Exner M, Bhattacharya S, Gebel J, Goroncy-Bermes P, Hartemann P, Heeg P, Ilschner C, Kramer A, Ling ML, Merkens W, Oltmanns P, Pitten F, Rotter M, Schmithausen RM, Sonntag HG, Steinhauer K, Trautmann M. Chemical disinfection in healthcare settings: critical aspects for the development of global strategies. GMS Hyg Infect Control. 2020 Dec 23;15:Doc36. DOI: 10.3205/dgkh000371