Synergism versus Additivity: Defining the Interactions between Common Disinfectants
Synergism versus Additivity: Defining the Interactions between Common Disinfectants
Many of the most common disinfectant and sanitizer products are formulations of multiple antimicrobial compounds. Products claiming to contain synergistic formulations are common, although there is often little supporting evidence. The antimicrobial interactions of all pairwise combinations of common disinfectants (benzalkonium chloride, didecyldimethylammonium chloride, polyhexamethylene biguanide, chlorocresol, and bronopol) were classified via checkerboard assay and validated by time-kill analyses. Combinations were tested against Acinetobacter baumannii NCTC 12156, Enterococcus faecalis NCTC 13379, Klebsiella pneumoniae NCTC 13443, and Staphylococcus aureus NCTC 13143. Synergistic interactions were identified only for the combinations of chlorocresol with benzalkonium chloride and chlorocresol with polyhexamethylene biguanide. Synergism was not ubiquitously demonstrated against all species tested and was on the borderline of the synergism threshold. These data demonstrate that synergism between disinfectants is uncommon and circumstantial. Most of the antimicrobial interactions tested were characterized as additive. We suggest that this is due to the broad, nonspecific mechanisms associated with disinfectants not providing an opportunity for the combined activities of these compounds to exceed the sum of their parts. IMPORTANCE The scarcity of observed synergistic interactions suggests that in the case of many disinfectant-based products, combined mechanisms of interaction may be being misinterpreted. We emphasize the need to correctly differentiate between additivity and synergism in antimicrobial formulations, as inappropriate classification may lead to unnecessary issues in the event of regulatory changes. Furthermore, we question the need to focus on synergism and disregard additivity when considering combinations of disinfectants, as the benefits that synergistic interactions provide are not necessarily relevant to the application of the final product.
additivity, antimicrobial activity, disinfectants, synergism, Additivity, Antimicrobial activity, Disinfectants, Synergism
e02281-21
Noel, Daniel J
d0f08b82-f171-4fe3-8c88-51ce63464ea3
Keevil, C William
cb7de0a7-ce33-4cfa-af52-07f99e5650eb
Wilks, Sandra A
86c1f41a-12b3-451c-9245-b1a21775e993
1 October 2021
Noel, Daniel J
d0f08b82-f171-4fe3-8c88-51ce63464ea3
Keevil, C William
cb7de0a7-ce33-4cfa-af52-07f99e5650eb
Wilks, Sandra A
86c1f41a-12b3-451c-9245-b1a21775e993
Noel, Daniel J, Keevil, C William and Wilks, Sandra A
(2021)
Synergism versus Additivity: Defining the Interactions between Common Disinfectants.
mBio, 12 (5), , [02281-21].
(doi:10.1128/mBio.02281-21).
Abstract
Many of the most common disinfectant and sanitizer products are formulations of multiple antimicrobial compounds. Products claiming to contain synergistic formulations are common, although there is often little supporting evidence. The antimicrobial interactions of all pairwise combinations of common disinfectants (benzalkonium chloride, didecyldimethylammonium chloride, polyhexamethylene biguanide, chlorocresol, and bronopol) were classified via checkerboard assay and validated by time-kill analyses. Combinations were tested against Acinetobacter baumannii NCTC 12156, Enterococcus faecalis NCTC 13379, Klebsiella pneumoniae NCTC 13443, and Staphylococcus aureus NCTC 13143. Synergistic interactions were identified only for the combinations of chlorocresol with benzalkonium chloride and chlorocresol with polyhexamethylene biguanide. Synergism was not ubiquitously demonstrated against all species tested and was on the borderline of the synergism threshold. These data demonstrate that synergism between disinfectants is uncommon and circumstantial. Most of the antimicrobial interactions tested were characterized as additive. We suggest that this is due to the broad, nonspecific mechanisms associated with disinfectants not providing an opportunity for the combined activities of these compounds to exceed the sum of their parts. IMPORTANCE The scarcity of observed synergistic interactions suggests that in the case of many disinfectant-based products, combined mechanisms of interaction may be being misinterpreted. We emphasize the need to correctly differentiate between additivity and synergism in antimicrobial formulations, as inappropriate classification may lead to unnecessary issues in the event of regulatory changes. Furthermore, we question the need to focus on synergism and disregard additivity when considering combinations of disinfectants, as the benefits that synergistic interactions provide are not necessarily relevant to the application of the final product.
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Accepted/In Press date: 17 August 2021
e-pub ahead of print date: 21 September 2021
Published date: 1 October 2021
Additional Information:
ACKNOWLEDGMENTS
Daniel J. Noel’s Ph.D. degree training was supported by a Southampton NIHR Academy Fellowship funded by NIHR Southampton Biomedical Research Centre and JVS Products Ltd., who were not involved in the work or in the writing of the paper.
Daniel J. Noel carried out and designed experimental work and data analysis and prepared the manuscript. C. William Keevil designed the study, reviewed the manuscript, and obtained funding. Sandra A. Wilks designed the study, reviewed the manuscript, and obtained funding.
Keywords:
additivity, antimicrobial activity, disinfectants, synergism, Additivity, Antimicrobial activity, Disinfectants, Synergism
Identifiers
Local EPrints ID: 451493
URI: http://eprints.soton.ac.uk/id/eprint/451493
ISSN: 2150-7511
PURE UUID: 1d70e821-69d2-406f-aac0-09ce16302829
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Date deposited: 01 Oct 2021 16:39
Last modified: 17 Mar 2024 02:54
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