Antiseptic Stewardship: Biocide Resistance and Clinical Implications

Preface
About the Book
Contents
About the Author
List of Abbreviations
1: Introduction
	1.1	 Background
	1.2	 Dimensions of Antiseptic Stewardship
	1.3	 Antiseptic Stewardship per Type of Application
	References
2: Definitions
	2.1	 Background
	2.2	 Tolerance
		2.2.1	 Definition
		2.2.2	 Distinction to Resistance
		2.2.3	 Other Definitions
	2.3	 Resistance
		2.3.1	 Definition
		2.3.2	 Other Definitions
	2.4	 Norms and Efficacy Requirements with Culture Collection Strains
		2.4.1	 Bactericidal Efficacy
		2.4.2	 Yeasticidal and Fungicidal Efficacy
		2.4.3	 Tuberculocidal and Mycobactericidal Efficacy
	References
3: Biofilm and Biocides
	3.1	 Types of Biofilms
		3.1.1	 Hydrated Biofilm
		3.1.2	 Build-Up Biofilm
		3.1.3	 Dry Surface Biofilm
	3.2	 Relevance of Biofilms for Biocides
	References
4: Ethanol
	4.1	 Chemical Characterisation
	4.2	 Types of Application
		4.2.1	 Application on Intact Skin
			4.2.1.1	 Hand Disinfection
			4.2.1.2	 Skin Antisepsis
			4.2.1.3	 European Chemicals Agency (European Union)
			4.2.1.4	 Food and Drug Administration (USA)
		4.2.2	 Application on Inanimate Surfaces
			4.2.2.1	 Surface Disinfection
			4.2.2.2	 Instrument Disinfection
			4.2.2.3	 European Chemicals Agency (European Union)
			4.2.2.4	 Environmental Protection Agency (USA)
		4.2.3	 Other Applications
	4.3	 Mechanism of Action
	4.4	 Spectrum of Antimicrobial Activity
		4.4.1	 Bactericidal Activity
			4.4.1.1	 Suspension Tests
			4.4.1.2	 MBC Values
			4.4.1.3	 Hygienic Hand Disinfection
			4.4.1.4	 Surgical Hand Disinfection
			4.4.1.5	 Surface Disinfection: Carrier Tests
			4.4.1.6	 Surface Disinfection: Wiping Test
		4.4.2	 Fungicidal Activity
			4.4.2.1	 Suspension Tests
			4.4.2.2	 Hygienic Hand Disinfection
			4.4.2.3	 Surface Disinfection: Carrier Tests
		4.4.3	 Mycobactericidal Activity
			4.4.3.1	 Suspension Tests
			4.4.3.2	 Surface Disinfection: Carrier Tests
			4.4.3.3	 Disinfection of Flexible Endoscopes
	4.5	 Mechanisms of Cellular Defence
		4.5.1	 Cell Membrane Changes
		4.5.2	 Resistance Genes
		4.5.3	 Efflux Pumps
		4.5.4	 Changes of Bacterial Motility
	4.6	 Effect on Biofilm
		4.6.1	 Effect on Developing Biofilm
			4.6.1.1	 Bacteria
			4.6.1.2	 Fungi
		4.6.2	 Effect on Existing Biofilm
			4.6.2.1	 Biofilm Mass
			4.6.2.2	 Biofilm Fixation
	4.7	 Tolerance to Ethanol
		4.7.1	 Release into the Environment
		4.7.2	 MIC Values
			4.7.2.1	 Bacteria: Culture Collection Strains
			4.7.2.2	 Bacteria: Human Isolates
			4.7.2.3	 Bacteria: Animal Isolates
			4.7.2.4	 Bacteria: Food Isolates
			4.7.2.5	 Bacteria: Environmental Isolates
			4.7.2.6	 Bacteria: Specific Strains
			4.7.2.7	 Fungi
		4.7.3	 Effect of Exposure to Subinhibitory Concentrations
			4.7.3.1	 Bacteria
			4.7.3.2	 Fungi
		4.7.4	 Elevated MIC Values
		4.7.5	 Cross-Tolerance to Other Biocidal Agents
	4.8	 Resistance to Ethanol
		4.8.1	 Insufficient Efficacy in Suspension Tests
		4.8.2	 Insufficient Efficacy Under Practical Conditions
		4.8.3	 Infections Associated with Resistant Isolates
		4.8.4	 Contamination of Disinfectants
		4.8.5	 Bacteria in Biofilms
		4.8.6	 Fungi in Biofilms
		4.8.7	 Mycobacteria in Biofilms
		4.8.8	 Cross-Resistance to Antibiotics
	4.9	 Summary
	References
5: Propan-1-ol
	5.1	 Chemical Characterisation
	5.2	 Types of Application
		5.2.1	 Application on Intact Skin
			5.2.1.1	 Hand Disinfection
			5.2.1.2	 Skin Antisepsis
			5.2.1.3	 European Chemicals Agency (European Union)
			5.2.1.4	 Food and Drug Administration (USA)
		5.2.2	 Application on Inanimate Surfaces
			5.2.2.1	 Surface Disinfection
			5.2.2.2	 Instrument Disinfection
			5.2.2.3	 European Chemicals Agency (European Union)
			5.2.2.4	 Environmental Protection Agency (USA)
		5.2.3	 Other Applications
	5.3	 Mechanism of Action
	5.4	 Spectrum of Antimicrobial Activity
		5.4.1	 Bactericidal Activity
			5.4.1.1	 Suspension Tests
			5.4.1.2	 Hygienic Hand Disinfection
			5.4.1.3	 Surgical Hand Disinfection
			5.4.1.4	 Skin Antisepsis
			5.4.1.5	 Surface Disinfection: Carrier Tests
			5.4.1.6	 Surface Disinfection: Wiping Test
		5.4.2	 Fungicidal Activity
			5.4.2.1	 Suspension Tests
			5.4.2.2	 Hygienic Hand Disinfection
			5.4.2.3	 Surface Disinfection: Carrier Tests
			5.4.2.4	 Surface Disinfection: Wiping Test
		5.4.3	 Mycobactericidal Activity
	5.5	 Mechanisms of Cellular Defence
	5.6	 Effect on Biofilm
		5.6.1	 Effect on Developing Biofilm
		5.6.2	 Effect on Existing Biofilm
			5.6.2.1	 Biofilm Mass
			5.6.2.2	 Biofilm Fixation
	5.7	 Tolerance to Propan-1-ol
		5.7.1	 Release into the Environment
		5.7.2	 MIC Values
			5.7.2.1	 Bacteria: Food Isolates
			5.7.2.2	 Fungi
		5.7.3	 Effect of Exposure to Subinhibitory Concentrations
			5.7.3.1	 Bacteria
			5.7.3.2	 Fungi
		5.7.4	 Elevated MIC Values
		5.7.5	 Cross-Tolerance to Other Biocidal Agents
	5.8	 Resistance to Propan-1-ol
		5.8.1	 Insufficient Efficacy
		5.8.2	 Bacteria in Biofilms
		5.8.3	 Cross-Resistance to Antibiotics
	5.9	 Summary
	References
6: Propan-2-ol
	6.1	 Chemical Characterisation
	6.2	 Types of Application
		6.2.1	 Application on Intact Skin
			6.2.1.1	 Hand Disinfection
			6.2.1.2	 Skin Antisepsis
			6.2.1.3	 European Chemicals Agency (European Union)
			6.2.1.4	 Food and Drug Administration (USA)
		6.2.2	 Application on Inanimate Surfaces
			6.2.2.1	 Surface Disinfection
			6.2.2.2	 Instrument Disinfection
			6.2.2.3	 European Chemicals Agency (European Union)
			6.2.2.4	 Environmental Protection Agency (USA)
		6.2.3	 Other Applications
	6.3	 Mechanism of Action
	6.4	 Spectrum of Antimicrobial Activity
		6.4.1	 Bactericidal Activity
			6.4.1.1	 Suspension Tests
			6.4.1.2	 MBC Values
			6.4.1.3	 Hygienic Hand Disinfection
			6.4.1.4	 Surgical Hand Disinfection
			6.4.1.5	 Surface Disinfection: Carrier Tests
			6.4.1.6	 Surface Disinfection: Wiping Test
		6.4.2	 Fungicidal Activity
			6.4.2.1	 Suspension Tests
		6.4.3	 Mycobactericidal Activity
			6.4.3.1	 Suspension Tests
	6.5	 Mechanisms of Cellular Defence
		6.5.1	 Cell Membrane Changes
		6.5.2	 Mutations
	6.6	 Effect on Biofilm
		6.6.1	 Effect on Developing Biofilm
			6.6.1.1	 Bacteria
		6.6.2	 Effect on Existing Biofilm
			6.6.2.1	 Biofilm Mass
			6.6.2.2	 Biofilm Fixation
	6.7	 Tolerance to Propan-2-ol
		6.7.1	 Release into the Environment
		6.7.2	 MIC Values
			6.7.2.1	 Bacteria: Culture Collection Strains
			6.7.2.2	 Bacteria: Human Isolates
			6.7.2.3	 Bacteria: Isolates from Animals, Food and the Environment
			6.7.2.4	 Fungi
		6.7.3	 Effect of Exposure to Subinhibitory Concentrations
			6.7.3.1	 Bacteria
			6.7.3.2	 Fungi
		6.7.4	 Elevated MIC Values
		6.7.5	 Cross-Tolerance to Other Biocidal Agents
	6.8	 Resistance to Propan-2-ol
		6.8.1	 Insufficient Efficacy in Suspension Tests
		6.8.2	 Insufficient Efficacy Under Practical Conditions
		6.8.3	 Infections Associated with Resistant Isolates
		6.8.4	 Contamination of Disinfectants
		6.8.5	 Bacteria in Biofilms
		6.8.6	 Cross-Resistance to Antibiotics
	6.9	 Summary
	References
7: Peracetic Acid
	7.1	 Chemical Characterisation
	7.2	 Types of Application
		7.2.1	 Application on Intact Skin
			7.2.1.1	 Hand Disinfection
			7.2.1.2	 Skin Antisepsis
			7.2.1.3	 European Chemicals Agency (European Union)
		7.2.2	 Application on Inanimate Surfaces
			7.2.2.1	 Surface Disinfection
			7.2.2.2	 Instrument Disinfection
			7.2.2.3	 European Chemicals Agency (European Union)
			7.2.2.4	 Environmental Protection Agency (USA)
		7.2.3	 Other Applications
	7.3	 Mechanism of Action
	7.4	 Spectrum of Antimicrobial Activity
		7.4.1	 Bactericidal Activity
			7.4.1.1	 Suspension Tests
			7.4.1.2	 MBC Values
			7.4.1.3	 Surface Disinfection: Carrier Tests
			7.4.1.4	 Bactericidal Activity in Endoscopes or Test Tubes
		7.4.2	 Fungicidal Activity
			7.4.2.1	 Suspension Tests
			7.4.2.2	 Surface Disinfection: Carrier Tests
			7.4.2.3	 Fungicidal Activity in Endoscopes or Test Tubes
		7.4.3	 Mycobactericidal Activity
			7.4.3.1	 Suspension Tests
			7.4.3.2	 Surface Disinfection: Carrier Tests
			7.4.3.3	 Disinfection of Flexible Endoscopes or Test Tubes
	7.5	 Mechanisms of Cellular Defence
	7.6	 Effect on Biofilm
		7.6.1	 Effect on Developing Biofilm
		7.6.2	 Effect on Existing Biofilm
			7.6.2.1	 Biofilm Mass
			7.6.2.2	 Biofilm Fixation
	7.7	 Tolerance to Peracetic Acid
		7.7.1	 Release into the Environment
		7.7.2	 MIC Values
			7.7.2.1	 Bacteria: Culture Collection Strains
			7.7.2.2	 Bacteria: Animal Isolates
			7.7.2.3	 Bacteria: Food Isolates
			7.7.2.4	 Bacteria: Environmental Isolates
			7.7.2.5	 Bacteria: Specific Strains
			7.7.2.6	 Bacteria: Various Sources
			7.7.2.7	 Fungi
		7.7.3	 Effect of Exposure to Subinhibitory Concentrations
			7.7.3.1	 Bacteria
		7.7.4	 Elevated MIC Values
		7.7.5	 Cross-tolerance to Other Biocidal Agents
	7.8	 Resistance to Peracetic Acid
		7.8.1	 Insufficient Efficacy in Suspension Tests
			7.8.1.1	 Bacteria
			7.8.1.2	 Mycobacteria
		7.8.2	 Insufficient Efficacy Under Practical Conditions
		7.8.3	 Infections Associated with Resistant Isolates
		7.8.4	 Contamination of Disinfectants
		7.8.5	 Bacteria in Biofilms
			7.8.5.1	 Escherichia coli
			7.8.5.2	 Listeria monocytogenes
			7.8.5.3	 Pseudomonas aeruginosa
			7.8.5.4	 Staphylococcus aureus
			7.8.5.5	 Staphylococcus epidermidis
			7.8.5.6	 Enterococcus spp.
			7.8.5.7	 Other Species
			7.8.5.8	 Mixed Species
		7.8.6	 Fungi in Biofilms
		7.8.7	 Mycobacteria in Biofilms
		7.8.8	 Cross-Resistance to Antibiotics
	7.9	 Summary
	References
8: Hydrogen Peroxide
	8.1	 Chemical Characterisation
	8.2	 Types of Application
		8.2.1	 Application on Intact Skin
			8.2.1.1	 Hand Disinfection
			8.2.1.2	 European Chemicals Agency (European Union)
			8.2.1.3	 Food and Drug Administration (USA)
		8.2.2	 Application on Inanimate Surfaces
			8.2.2.1	 Surface Disinfection
			8.2.2.2	 Instrument Disinfection
			8.2.2.3	 European Chemicals Agency (European Union)
			8.2.2.4	 Environmental Protection Agency (USA)
		8.2.3	 Other Applications
	8.3	 Mode of Action
	8.4	 Spectrum of Antimicrobial Activity
		8.4.1	 Bactericidal Activity
			8.4.1.1	 Suspension Tests
			8.4.1.2	 MBC Values
			8.4.1.3	 Surface Disinfection: Carrier Tests
			8.4.1.4	 Surface Disinfection: Wiping Test
			8.4.1.5	 Bactericidal Activity of Fumigation
			8.4.1.6	 Bactericidal Activity in Other Applications
		8.4.2	 Fungicidal Activity
			8.4.2.1	 Suspension Tests
			8.4.2.2	 Surface Disinfection: Carrier Tests
			8.4.2.3	 Fungicidal Activity in Other Applications
		8.4.3	 Mycobactericidal Activity
			8.4.3.1	 Suspension Tests
			8.4.3.2	 Surface Disinfection: Carrier Tests
			8.4.3.3	 Disinfection of Flexible Endoscopes
	8.5	 Mechanisms of Cellular Defence
		8.5.1	 Peroxidases and Catalases
		8.5.2	 Resistance Genes
		8.5.3	 Persister Cell Formation
	8.6	 Effect on Biofilm
		8.6.1	 Effect on Developing Biofilm
			8.6.1.1	 Bacteria
			8.6.1.2	 Fungi
		8.6.2	 Effect on Existing Biofilm
			8.6.2.1	 Biofilm Mass
			8.6.2.2	 Biofilm Fixation
	8.7	 Tolerance to Hydrogen Peroxide
		8.7.1	 Release into the Environment
		8.7.2	 MIC Values
			8.7.2.1	 Bacteria: Culture Collection Strains
			8.7.2.2	 Bacteria: Human Isolates
			8.7.2.3	 Bacteria: Animal Isolates
			8.7.2.4	 Bacteria: Food Isolates
			8.7.2.5	 Bacteria—Environmental Isolates
			8.7.2.6	 Bacteria-Specific Strains
			8.7.2.7	 Fungi
		8.7.3	 Effect of Exposure to Subinhibitory Concentrations
			8.7.3.1	 Bacteria
			8.7.3.2	 Fungi
			8.7.3.3	 Mycobacteria
		8.7.4	 Elevated MIC Values
		8.7.5	 Cross-Tolerance to Other Biocidal Agents
	8.8	 Resistance to Hydrogen Peroxide
		8.8.1	 Insufficient Efficacy in Suspension Tests
		8.8.2	 Insufficient Efficacy under Practical Conditions
		8.8.3	 Infections Associated with Resistant Isolates
		8.8.4	 Contamination of Disinfectants
		8.8.5	 Bacteria in Biofilms
		8.8.6	 Fungi in Biofilms
		8.8.7	 Mycobacteria in Biofilms
		8.8.8	 Cross-Resistance to Antibiotics
	8.9	 Summary
	References
9: Glutaraldehyde
	9.1	 Chemical Characterisation
	9.2	 Types of Application
		9.2.1	 Application on Inanimate Surfaces
			9.2.1.1	 Surface Disinfection
			9.2.1.2	 Instrument Disinfection
			9.2.1.3	 European Chemicals Agency (European Union)
			9.2.1.4	 Environmental Protection Agency (USA)
		9.2.2	 Other Applications
	9.3	 Mode of Action
	9.4	 Spectrum of Antimicrobial Activity
		9.4.1	 Bactericidal Activity
			9.4.1.1	 Suspension Tests
			9.4.1.2	 MBC Values
			9.4.1.3	 Surface Disinfection: Carrier Tests
			9.4.1.4	 Bactericidal Activity in Endoscopes or Test Tubes
			9.4.1.5	 Bactericidal Activity in Other Applications
		9.4.2	 Fungicidal Activity
			9.4.2.1	 Suspension Tests
			9.4.2.2	 Surface Disinfection: Carrier Tests
		9.4.3	 Mycobactericidal Activity
			9.4.3.1	 Suspension Tests
			9.4.3.2	 Surface Disinfection: Carrier Tests
			9.4.3.3	 Disinfection of Flexible Endoscopes
	9.5	 Mechanisms of Cellular Defence
		9.5.1	 Cell Membrane Changes
		9.5.2	 Resistance Genes
		9.5.3	 Efflux Pumps
		9.5.4	 Tolerance Plasmids
	9.6	 Effect on Biofilm
		9.6.1	 Effect on Developing Biofilm
		9.6.2	 Effect on Existing Biofilm
			9.6.2.1	 Biofilm Mass
			9.6.2.2	 Biofilm Fixation
	9.7	 Tolerance to Glutaraldehyde
		9.7.1	 Release into the Environment
		9.7.2	 MIC Values
			9.7.2.1	 Bacteria: Culture Collection Strains
			9.7.2.2	 Bacteria: Human Isolates
			9.7.2.3	 Bacteria: Animal Isolates
			9.7.2.4	 Bacteria-Specific Strains and Isolates from Different Sources
		9.7.3	 Effect of Exposure to Subinhibitory Concentrations
			9.7.3.1	 Bacteria
		9.7.4	 Elevated MIC Values
		9.7.5	 Cross-Tolerance to Other Biocidal Agents
	9.8	 Resistance to Glutaraldehyde
		9.8.1	 Insufficient Efficacy in Suspension Tests
			9.8.1.1	 Bacteria
			9.8.1.2	 Mycobacteria
		9.8.2	 Insufficient Efficacy under Practical Conditions
		9.8.3	 Infections Associated with Resistant Isolates
		9.8.4	 Bacteria in Biofilms
		9.8.5	 Fungi in Biofilms
		9.8.6	 Mycobacteria in Biofilms
		9.8.7	 Cross-Resistance to Antibiotics
	9.9	 Summary
	References
10: Sodium Hypochlorite
	10.1	 Chemical Characterisation
	10.2	 Types of Application
		10.2.1	 Application on Intact Skin
			10.2.1.1	 Hand Disinfection
			10.2.1.2	 Skin Antisepsis
			10.2.1.3	 European Chemicals Agency (European Union)
			10.2.1.4	 Food and Drug Administration (USA)
		10.2.2	 Application on Inanimate Surfaces
			10.2.2.1	 Surface Disinfection
			10.2.2.2	 Instrument Disinfection
			10.2.2.3	 European Chemicals Agency (European Union)
			10.2.2.4	 Environmental Protection Agency (USA)
		10.2.3	 Other Applications
	10.3	 Mode of Action
	10.4	 Spectrum of Antimicrobial Activity
		10.4.1	 Bactericidal Activity
			10.4.1.1	 Suspension Tests
			10.4.1.2	 MBC Values
			10.4.1.3	 Hygienic Hand Disinfection
			10.4.1.4	 Surface Disinfection: Carrier Tests
			10.4.1.5	 Surface Disinfection: Wiping Test
			10.4.1.6	 Bactericidal Activity in Other Applications
		10.4.2	 Fungicidal Activity
			10.4.2.1	 Suspension Tests
			10.4.2.2	 Surface Disinfection: Carrier Tests
			10.4.2.3	 Fungicidal Activity in Other Applications
		10.4.3	 Mycobactericidal Activity
			10.4.3.1	 Suspension Tests
			10.4.3.2	 Surface Disinfection: Carrier Tests
	10.5	 Mechanisms of Cellular Defence
	10.6	 Effect on Biofilm
		10.6.1	 Effect on Developing Biofilm
			10.6.1.1	 Bacteria
			10.6.1.2	 Fungi
		10.6.2	 Effect on Existing Biofilm
			10.6.2.1	 Biofilm Mass
			10.6.2.2	 Biofilm Fixation
	10.7	 Tolerance to Sodium Hypochlorite
		10.7.1	 Release into the Environment
		10.7.2	 MIC Values
			10.7.2.1	 Bacteria: Culture Collection Strains
			10.7.2.2	 Bacteria: Human Isolates
			10.7.2.3	 Bacteria: Animal Isolates
			10.7.2.4	 Bacteria: Food Isolates
			10.7.2.5	 Bacteria: Environmental Isolates
			10.7.2.6	 Bacteria: Specific Strains or Different Sources
			10.7.2.7	 Fungi
		10.7.3	 Effect of Exposure to Subinhibitory Concentrations
			10.7.3.1	 Bacteria
		10.7.4	 Elevated MIC Values
		10.7.5	 Cross-Tolerance to Other Biocidal Agents
	10.8	 Resistance to Sodium Hypochlorite
		10.8.1	 Insufficient Efficacy in Suspension Tests
		10.8.2	 Insufficient Efficacy Under Practical Conditions
		10.8.3	 Infections Associated with Resistant Isolates
		10.8.4	 Contamination of Disinfectants
		10.8.5	 Bacteria in Biofilms
		10.8.6	 Fungi in Biofilms
		10.8.7	 Mycobacteria in Biofilms
		10.8.8	 Cross-Resistance to Antibiotics
	10.9	 Summary
	References
11: Triclosan
	11.1	 Chemical Characterisation
	11.2	 Types of Application
		11.2.1	 Application on Intact Skin
			11.2.1.1	 Hand Hygiene
			11.2.1.2	 Antiseptic Body Washing
			11.2.1.3	 European Chemicals Agency (European Union)
			11.2.1.4	 Food and Drug Administration (USA)
		11.2.2	 Application on Inanimate Surfaces
			11.2.2.1	 Impregnated Sutures
			11.2.2.2	 Environmental Protection Agency (USA)
		11.2.3	 Other Applications
	11.3	 Mode of Action
	11.4	 Spectrum of Antimicrobial Activity
		11.4.1	 Bactericidal Activity
			11.4.1.1	 Suspension Tests
			11.4.1.2	 Hygienic Hand Wash
			11.4.1.3	 Surgical Hand Disinfection
			11.4.1.4	 Carrier Tests
			11.4.1.5	 Impregnated Sutures
		11.4.2	 Fungicidal Activity
			11.4.2.1	 Suspension Tests
		11.4.3	 Mycobactericidal Activity
			11.4.3.1	 Suspension Tests
			11.4.3.2	 Outbreak Control
	11.5	 Mechanisms of Cellular Defence
		11.5.1	 Cell Membrane Changes
		11.5.2	 Resistance Genes
		11.5.3	 Efflux Pumps
		11.5.4	 Plasmids
		11.5.5	 Use of Triclosan as Carbon Source
	11.6	 Effect on Biofilm
		11.6.1	 Effect on Developing Biofilm
			11.6.1.1	 Bacteria
			11.6.1.2	 Fungi
		11.6.2	 Effect on Existing Biofilm
			11.6.2.1	 Biofilm Mass
			11.6.2.2	 Biofilm Fixation
	11.7	 Tolerance to Triclosan
		11.7.1	 Release into the Environment
		11.7.2	 MIC Values
			11.7.2.1	 Bacteria: Culture Collection Strains
			11.7.2.2	 Bacteria: Human Isolates
			11.7.2.3	 Bacteria: Animal Isolates
			11.7.2.4	 Bacteria: Food Isolates
			11.7.2.5	 Bacteria: Environmental Isolates
			11.7.2.6	 Bacteria: Specific Strains and Different Sources
			11.7.2.7	 Bacteria: Isolates with Suspected Triclosan Tolerance
			11.7.2.8	 Fungi
			11.7.2.9	 Mycobacteria
		11.7.3	 Effect of Exposure to Subinhibitory Concentrations
			11.7.3.1	 Bacteria
		11.7.4	 Elevated MIC Values
		11.7.5	 Cross-Tolerance to Other Biocidal Agents
	11.8	 Resistance to Triclosan
		11.8.1	 Insufficient Efficacy in Suspension Tests
		11.8.2	 Insufficient Efficacy under Practical Conditions
		11.8.3	 Infections Associated with Resistant Isolates
		11.8.4	 Contamination of Disinfectants
		11.8.5	 Bacteria in Biofilms
		11.8.6	 Fungi in Biofilms
		11.8.7	 Cross-Resistance to Antibiotics
	11.9	 Summary
	References
12: Benzalkonium Chloride
	12.1	 Chemical Characterisation
	12.2	 Types of Application
		12.2.1	 Application on Intact Skin
			12.2.1.1	 Hand Disinfection
			12.2.1.2	 Skin Antisepsis
			12.2.1.3	 European Chemicals Agency (European Union)
			12.2.1.4	 Food and Drug Administration (USA)
		12.2.2	 Application on Inanimate Surfaces
			12.2.2.1	 Surface Disinfection
			12.2.2.2	 Instrument Disinfection
			12.2.2.3	 European Chemicals Agency (European Union)
			12.2.2.4	 Environmental Protection Agency (USA)
		12.2.3	 Other Applications
			12.2.3.1 Wound and Mucous Membrane Antisepsis
			12.2.3.2	 Veterinary Medicine
			12.2.3.3	 Wood Preservative
			12.2.3.4	European Chemicals Agency (European Union)
	12.3	 Mode of Action
	12.4	 Spectrum of Antimicrobial Activity
		12.4.1	 Bactericidal Activity
			12.4.1.1	 Suspension Tests
			12.4.1.2	 MBC Values
			12.4.1.3	 Hygienic Hand Disinfection
			12.4.1.4	 Surface Disinfection: Carrier Tests
			12.4.1.5	 Surface Disinfection: Wiping Test
		12.4.2	 Fungicidal Activity
			12.4.2.1	 Suspension Tests
			12.4.2.2	 Surface Disinfection: Carrier Tests
			12.4.2.3	 Surface Disinfection: Wiping Test
		12.4.3	 Mycobactericidal Activity
			12.4.3.1	 Suspension Tests
	12.5	 Mechanisms of Cellular Defence
		12.5.1	 Cell Membrane Changes
		12.5.2	 Resistance Genes
			12.5.2.1	 qacA/B
			12.5.2.2	 smr (qacC)
			12.5.2.3	 qacE and qacEΔ
			12.5.2.4	 qacF
			12.5.2.5	 qacG
			12.5.2.6	 qacH
			12.5.2.7	 qacJ
			12.5.2.8	 emrC
			12.5.2.9	 emrE
			12.5.2.10	 SigB
			12.5.2.11	 mdfA
			12.5.2.12	 SugE(C)
			12.5.2.13	 ydgE
			12.5.2.14	 ydgF
		12.5.3	 Efflux Pumps
		12.5.4	 Plasmids for Transfer of Defence Mechanisms
			12.5.4.1	 pSK1
			12.5.4.2	 pSK41
			12.5.4.3	 pSK108
			12.5.4.4	 pLM80
			12.5.4.5	 pSP187
			12.5.4.6	 pNVH01
			12.5.4.7	 pST94
			12.5.4.8	 pST827
			12.5.4.9	 pSx1
			12.5.4.10	 pLMST6_emrC
		12.5.5	 Transposons for Resistance Transfer
		12.5.6	 Class I Integrons
	12.6	 Effect on Biofilm
		12.6.1	 Effect on Developing Biofilm
			12.6.1.1	 Bacteria
		12.6.2	 Effect on Existing Biofilm
			12.6.2.1	 Biofilm Mass
			12.6.2.2	 Biofilm Fixation
	12.7	 Tolerance to Benzalkonium Chloride
		12.7.1	 Release into the Environment
		12.7.2	 MIC Values
			12.7.2.1	 Bacteria Culture Collection Strains
			12.7.2.2	 Bacteria: Human Isolates
			12.7.2.3	 Bacteria: Animal Isolates
			12.7.2.4	 Bacteria: Food Isolates
			12.7.2.5	 Bacteria: Environmental Isolates
			12.7.2.6	 Bacteria: Strains with Resistance Genes or “Resistance”
			12.7.2.7	 Bacteria: Specific Strains and Isolates from Different Sources
			12.7.2.8	 Bacteria: Biofilm Grown Isolates
			12.7.2.9	 Fungi
		12.7.3	 Effect of Exposure to Subinhibitory Concentrations
			12.7.3.1	 Change of Susceptibility to BAC
			12.7.3.2	 Other Changes
		12.7.4	 Elevated MIC Values
		12.7.5	 Cross-Tolerance to Other Biocidal Agents
	12.8	 Resistance to Benzalkonium Chloride
		12.8.1	 Insufficient Efficacy in Suspension Tests
		12.8.2	 Insufficient Efficacy Under Practical Conditions
		12.8.3	 Infections Associated with Resistant Isolates
		12.8.4	 Contamination of Disinfectants
		12.8.5	 Bacteria in Biofilms
		12.8.6	 Fungi in Biofilms
		12.8.7	 Cross-Resistance to Antibiotics
	12.9	 Summary
	References
13: Didecyldimethylammonium Chloride
	13.1	 Chemical Characterisation
	13.2	 Types of Application
		13.2.1	 Application on Intact Skin
			13.2.1.1	 Hand Disinfection
			13.2.1.2	 European Chemicals Agency (European Union)
			13.2.1.3	 Food and Drug Administration (USA)
		13.2.2	 Application on Inanimate Surfaces
			13.2.2.1	 Surface Disinfection
			13.2.2.2	 Instrument Disinfection
			13.2.2.3	 European Chemicals Agency (European Union)
			13.2.2.4	 Environmental Protection Agency (USA)
		13.2.3	 Other Applications
	13.3	 Mode of Action
	13.4	 Spectrum of Antimicrobial Activity
		13.4.1	 Bactericidal Activity
			13.4.1.1	 Suspension Tests
			13.4.1.2	 MBC Values
			13.4.1.3	 Surface Disinfection: Carrier Tests
			13.4.1.4	 Surface Disinfection: Wiping Test
		13.4.2	 Fungicidal Activity
			13.4.2.1	 Suspension Tests
			13.4.2.2	 Surface Disinfection: Wiping Tests
		13.4.3	 Mycobactericidal Activity
			13.4.3.1	 Suspension Tests
	13.5	 Mechanisms of Cellular Defence
		13.5.1	 Resistance Genes
		13.5.2	 Efflux Pumps
		13.5.3	 Metabolisation of DDAC
	13.6	 Effect on Biofilm
		13.6.1	 Effect on Developing Biofilm
		13.6.2	 Effect on Existing Biofilm
			13.6.2.1	 Biofilm Mass
			13.6.2.2	 Biofilm Fixation
	13.7	 Tolerance to Didecyldimethylammonium Chloride
		13.7.1	 Release into the Environment
		13.7.2	 MIC Values
			13.7.2.1	 Bacteria: Culture Collection Strains
			13.7.2.2	 Bacteria: Human Isolates
			13.7.2.3	 Bacteria: Animal Isolates
			13.7.2.4	 Bacteria: Food Isolates
			13.7.2.5	 Bacteria: Environmental Isolates
			13.7.2.6	 Bacteria: Specific Strains and Various Sources
			13.7.2.7	 Fungi
		13.7.3	 Effect of Exposure to Subinhibitory Concentrations
			13.7.3.1	 Bacteria
		13.7.4	 Elevated MIC Values
		13.7.5	 Cross-Tolerance to Other Biocidal Agents
	13.8	 Resistance to Didecyldimethylammonium Chloride
		13.8.1	 Insufficient Efficacy in Suspension Tests
		13.8.2	 Insufficient Efficacy Under Practical Conditions
		13.8.3	 Infections Associated with Resistant Isolates
		13.8.4	 Contamination of Disinfectants
		13.8.5	 Bacteria in Biofilms
		13.8.6	 Fungi in Biofilms
		13.8.7	 Cross-Resistance to Antibiotics
	13.9	 Summary
	References
14: Polihexanide
	14.1	 Chemical Characterisation
	14.2	 Types of Application
		14.2.1	 Application on Intact Skin
			14.2.1.1	 Hand Hygiene
			14.2.1.2	 European Chemicals Agency (European Union)
		14.2.2	 Application on Non-intact Skin
		14.2.3	 Other Applications
	14.3	 Mode of Action
	14.4	 Spectrum of Antimicrobial Activity
		14.4.1	 Bactericidal Activity
			14.4.1.1	 Suspension Tests
			14.4.1.2	 MBC Values
			14.4.1.3	 Bactericidal Activity on Skin
			14.4.1.4	 Bactericidal Activity on Mucosa
			14.4.1.5	 Bactericidal Activity on Wounds
			14.4.1.6	 Bactericidal Activity of Impregnated Gloves
			14.4.1.7	 Surface Disinfection: Carrier Tests
		14.4.2	 Fungicidal Activity
			14.4.2.1	 Suspension Tests
		14.4.3	 Mycobactericidal Activity
			14.4.3.1	 Suspension Tests
	14.5	 Mechanisms of Cellular Defence
		14.5.1	 Resistance Genes
		14.5.2	 Biodegradation
		14.5.3	 Point Mutation
	14.6	 Effect on Biofilm
		14.6.1	 Effect on Developing Biofilm
		14.6.2	 Effect on Existing Biofilm
			14.6.2.1	 Biofilm Mass
			14.6.2.2	 Biofilm Fixation
	14.7	 Tolerance to PHMB
		14.7.1	 Release into the Environment
		14.7.2	 MIC Values
			14.7.2.1	 Bacteria: Culture Collection Strains
			14.7.2.2	 Bacteria: Human Isolates
			14.7.2.3	 Bacteria: Animal Isolates
			14.7.2.4	 Bacteria: Environmental Isolates
			14.7.2.5	 Bacteria: Specific Strains and Different Sources
			14.7.2.6	 Fungi
		14.7.3	 Effect of Exposure to Subinhibitory Concentrations
			14.7.3.1	 Bacteria
		14.7.4	 Elevated MIC Values
		14.7.5	 Cross-Tolerance to Other Biocidal Agents
	14.8	 Resistance to Polihexanide
		14.8.1	 Insufficient Efficacy in Suspension Tests
		14.8.2	 Insufficient Efficacy Under Practical Conditions
		14.8.3	 Infections Associated with Resistant Isolates
		14.8.4	 Contamination of Disinfectants
		14.8.5	 Bacteria in Biofilms
		14.8.6	 Fungi in Biofilms
		14.8.7	 Cross-Resistance to Antibiotics
	14.9	 Summary
	References
15: Chlorhexidine Digluconate
	15.1	 Chemical Characterisation
	15.2	 Types of Application
		15.2.1	 Application on Intact Skin
			15.2.1.1	 Hand Disinfection
			15.2.1.2	 Skin Antisepsis
			15.2.1.3	 European Chemicals Agency (European Union)
			15.2.1.4	 Food and Drug Administration (USA)
		15.2.2	 Application on Non-intact Skin
		15.2.3	 Other Uses
	15.3	 Mode of Action
	15.4	 Spectrum of Antimicrobial Activity
		15.4.1	 Bactericidal Activity
			15.4.1.1	 Suspension Tests
			15.4.1.2	 MBC Values
			15.4.1.3	 Hygienic Hand Disinfection
			15.4.1.4	 Bactericidal Activity in Antiseptic Soaps
			15.4.1.5	 Bactericidal Activity on Skin
			15.4.1.6	 Activity Against Bacteria on Mucosa
			15.4.1.7	 Surface Disinfection: Carrier Tests
		15.4.2	 Fungicidal Activity
			15.4.2.1	 Suspension Tests
			15.4.2.2	 Surface Disinfection: Carrier Tests
			15.4.2.3	 Yeasticidal Activity on Skin
		15.4.3	 Mycobactericidal Activity
			15.4.3.1	 Suspension Tests
			15.4.3.2	 Surface Disinfection: Carrier Tests
	15.5	 Mechanisms of Cellular Defence
		15.5.1	 Cell Membrane Changes
		15.5.2	 Resistance Genes
			15.5.2.1	 qacA/B
			15.5.2.2	 qacE
			15.5.2.3	 smr (qacC)
			15.5.2.4	 Other Resistance Genes
		15.5.3	 Efflux Pumps
		15.5.4	 Plasmids
		15.5.5	 Class I Integrons
	15.6	 Effect on Biofilm
		15.6.1	 Effect on Developing Biofilm
			15.6.1.1	 Bacteria
		15.6.2	 Effect on Existing Biofilm
			15.6.2.1	 Biofilm Mass
			15.6.2.2	 Biofilm Fixation
	15.7	 Tolerance to Chlorhexidine Digluconate
		15.7.1	 Release into the Environment
		15.7.2	 MIC Values
			15.7.2.1	 Bacteria: Culture Collection Strains
			15.7.2.2	 Bacteria: Human Isolates
			15.7.2.3	 Bacteria: Animal Isolates
			15.7.2.4	 Bacteria: Food Isolates
			15.7.2.5	 Bacteria: Environmental Isolates
			15.7.2.6	 Bacteria: Specific Strains and Different Sources
			15.7.2.7	 Bacteria: “Tolerant” Isolates
			15.7.2.8	 Fungi
		15.7.3	 Effect of Exposure to Subinhibitory Concentrations
			15.7.3.1	 Bacteria
			15.7.3.2	 Fungi
		15.7.4	 Elevated MIC Values
		15.7.5	 Cross-Tolerance to Other Biocidal Agents
	15.8	 Resistance to Chlorhexidine Digluconate
		15.8.1	 Insufficient Efficacy in Suspension Tests
		15.8.2	 Insufficient Efficacy Under Practical Conditions
		15.8.3	 Infections Associated with Resistant Isolates
		15.8.4	 Contamination of Disinfectants
		15.8.5	 Bacteria in Biofilms
		15.8.6	 Fungi in Biofilms
		15.8.7	 Cross-Resistance to Antibiotics
	15.9	 Summary
	References
16: Octenidine Dihydrochloride
	16.1	 Chemical Characterisation
	16.2	 Types of Application
		16.2.1	 Application on Intact Skin
			16.2.1.1	 Hand Disinfection and Hand Washing
			16.2.1.2	 Skin Antisepsis
			16.2.1.3	 European Chemicals Agency (European Union)
			16.2.1.4	 Food and Drug Administration (USA)
		16.2.2	 Application on Mucosa and Wounds
			16.2.2.1	 Antisepsis of Mucosa
			16.2.2.2	 Antisepsis of Wounds
			16.2.2.3	 European Chemicals Agency (European Union)
			16.2.2.4	 Environmental Protection Agency (USA)
		16.2.3	 Other Applications
	16.3	 Mode of Action
	16.4	 Spectrum of Antimicrobial Activity
		16.4.1	 Bactericidal Activity
			16.4.1.1	 Suspension Tests
			16.4.1.2	 MBC Values
			16.4.1.3	 Bactericidal Activity on Skin
			16.4.1.4	 Bactericidal Activity of Mouth Rinse Solution
			16.4.1.5	 Surface Disinfection: Carrier Tests
			16.4.1.6	 Bactericidal Activity in Other Applications
		16.4.2	 Fungicidal Activity
			16.4.2.1	 Suspension Tests
			16.4.2.2	 Fungicidal Activity on Skin
		16.4.3	 Mycobactericidal Activity
	16.5	 Mechanisms of Cellular Defence
		16.5.1	 Resistance Genes
		16.5.2	 Efflux Pumps
	16.6	 Effect on Biofilm
		16.6.1	 Effect on Developing Biofilm
			16.6.1.1	 Bacteria
		16.6.2	 Effect on Existing Biofilm
			16.6.2.1	 Biofilm Mass
			16.6.2.2	 Biofilm Fixation
	16.7	 Tolerance to Octenidine Dihydrochloride
		16.7.1	 Release into the Environment
		16.7.2	 MIC Values
			16.7.2.1	 Bacteria: Culture Collection Strains
			16.7.2.2	 Bacteria: Human Isolates
			16.7.2.3	 Bacteria: Other Sources
			16.7.2.4	 Fungi
			16.7.2.5	 Mycobacteria
		16.7.3	 Effect of Exposure to Subinhibitory Concentrations
			16.7.3.1	 Bacteria
		16.7.4	 Elevated MIC Values
		16.7.5	 Cross-Tolerance to Other Biocidal Agents
	16.8	 Resistance to Octenidine Dihydrochloride
		16.8.1	 Insufficient Efficacy in Suspension Tests
		16.8.2	 Insufficient Efficacy Under Practical Conditions
		16.8.3	 Infections Associated with Resistant Isolates
		16.8.4	 Contamination of Disinfectants
		16.8.5	 Bacteria in Biofilms
		16.8.6	 Fungi in Biofilms
		16.8.7	 Cross-Resistance to Antibiotics
	16.9	 Summary
	References
17: Silver
	17.1	 Chemical Characterisation
	17.2	 Types of Application
		17.2.1	 Different Applications
		17.2.2	 European Chemicals Agency (European Union)
		17.2.3	 Environmental Protection Agency (USA)
	17.3	 Mode of Action
	17.4	 Spectrum of Antimicrobial Activity
		17.4.1	 Bactericidal Activity
			17.4.1.1	 Suspension Tests
			17.4.1.2	 Bactericidal Activity in Wound Dressings
			17.4.1.3	 Bactericidal Activity in Other Applications
		17.4.2	 Fungicidal Activity
		17.4.3	 Mycobactericidal Activity
			17.4.3.1	 Suspension Tests
	17.5	 Mechanisms of Cellular Defence
		17.5.1	 Resistance Genes
			17.5.1.1	 silE
			17.5.1.2	 silA
			17.5.1.3	 silP
			17.5.1.4	 silS
			17.5.1.5	 Various sil Genes
		17.5.2	 Efflux Pumps
		17.5.3	 Plasmids
			17.5.3.1	 pMG101
			17.5.3.2	 pJT1 and pJT2
			17.5.3.3	 pSTM6-275
			17.5.3.4	 pUPI199
			17.5.3.5	 pKQPS142
			17.5.3.6	 pLVPK
			17.5.3.7	 pUUH239.2
			17.5.3.8	 Megaplasmids
		17.5.4	 Silver Uptake and Accumulation
	17.6	 Effect on Biofilm
		17.6.1	 Effect on Developing Biofilm
			17.6.1.1	 Bacteria
			17.6.1.2	 Fungi
		17.6.2	 Effect on Existing Biofilm
			17.6.2.1	 Biofilm Mass
			17.6.2.2	 Biofilm Fixation
	17.7	 Tolerance to Silver
		17.7.1	 Release into the Environment
		17.7.2	 MIC Values
			17.7.2.1	 Bacteria: Culture Collection Strains
			17.7.2.2	 Bacteria: Human Isolates
			17.7.2.3	 Bacteria: Animal Isolates
			17.7.2.4	 Bacteria: Food Isolates
			17.7.2.5	 Bacteria: Environmental Isolates
			17.7.2.6	 Bacteria: Specific Strains and Different Sources
			17.7.2.7	 Bacteria: “Tolerant” Isolates
			17.7.2.8	 Fungi
			17.7.2.9	 Mycobacteria
		17.7.3	 Effect of Exposure to Subinhibitory Concentrations
			17.7.3.1	 Bacteria
		17.7.4	 Elevated MIC Values
		17.7.5	 Cross-Tolerance to Other Biocidal Agents
	17.8	 Resistance to Silver
		17.8.1	 Insufficient Efficacy in Suspension Tests
		17.8.2	 Insufficient Efficacy Under Practical Conditions
		17.8.3	 Infections Associated with Resistant Isolates
		17.8.4	 Contamination of Disinfectants
		17.8.5	 Bacteria in Biofilms
		17.8.6	 Fungi in Biofilms
		17.8.7	 Cross-Resistance to Antibiotics
			17.8.7.1	 Clinical Isolates
			17.8.7.2	 Environmental Isolates
			17.8.7.3	 Cross-Resistance by Plasmids
	17.9	 Summary
	References
18: Povidone Iodine
	18.1	 Chemical Characterisation
	18.2	 Types of Application
		18.2.1	 Application on Intact Skin
			18.2.1.1	 Hand Disinfection
			18.2.1.2	 Skin Antisepsis
			18.2.1.3	 European Chemicals Agency (European Union)
			18.2.1.4	 Food and Drug Administration (USA)
		18.2.2	 Application on Wounds and Mucosa
		18.2.3	 Other Applications
			18.2.3.1	 Environmental Protection Agency (USA)
	18.3	 Mode of Action
	18.4	 Spectrum of Antimicrobial Activity
		18.4.1	 Bactericidal Activity
			18.4.1.1	 Suspension Tests
			18.4.1.2	 MBC Values
			18.4.1.3	 Bactericidal Activity in Surgical Scrubbing
			18.4.1.4	 Surface Disinfection: Carrier Tests
			18.4.1.5	 Bactericidal Activity on Skin
			18.4.1.6	 Bactericidal Activity in Other Applications
		18.4.2	 Fungicidal Activity
			18.4.2.1	 Suspension Tests
		18.4.3	 Mycobactericidal Activity
			18.4.3.1	 Suspension Tests
			18.4.3.2	 Surface Disinfection: Carrier Tests
	18.5	 Mechanisms of Cellular Defence
	18.6	 Effect on Biofilm
		18.6.1	 Effect on Developing Biofilm
			18.6.1.1	 Bacteria
		18.6.2	 Effect on Existing Biofilm
			18.6.2.1	 Biofilm Mass
			18.6.2.2	 Biofilm Fixation
	18.7	 Tolerance to Povidone Iodine
		18.7.1	 Release into the Environment
		18.7.2	 MIC Values
			18.7.2.1	 Bacteria: Culture Collection Strains
			18.7.2.2	 Bacteria: Human Isolates
			18.7.2.3	 Bacteria: Animal Isolates
			18.7.2.4	 Bacteria: Environmental Isolates
			18.7.2.5	 Bacteria: Specific Strains and Various Sources
			18.7.2.6	 Fungi
		18.7.3	 Effect of Exposure to Subinhibitory Concentrations
			18.7.3.1	 Bacteria
		18.7.4	 Elevated MIC Values
		18.7.5	 Cross-Tolerance to Other Biocidal Agents
	18.8	 Resistance to Povidone Iodine
		18.8.1	 Insufficient Efficacy in Suspension Tests
		18.8.2	 Insufficient Efficacy Under Practical Conditions
		18.8.3	 Infections Associated with Resistant Isolates
		18.8.4	 Contamination of Disinfectants
		18.8.5	 Bacteria in Biofilms
		18.8.6	 Fungi in Biofilms
		18.8.7	 Cross-Resistance to Antibiotics
	18.9	 Summary
	References
19: Antiseptic Stewardship for Alcohol-Based Hand Rubs
	19.1	 Composition and Intended Use
	19.2	 Selection Pressure Associated with Commonly Used Biocidal Active Substances
		19.2.1	 Change of Susceptibility by Low-Level Exposure
		19.2.2	 Cross-Tolerance to Other Biocidal Active Substances
		19.2.3	 Efflux Pump Genes
		19.2.4	 Tolerance Gene Plasmids
		19.2.5	 Horizontal Gene Transfer
		19.2.6	 Viable but Not Culturable
		19.2.7	 Antibiotic Resistance Gene Expression
		19.2.8	 Other Risks Associated with Additional Biocidal Active Substances
	19.3	 Health Benefit of Biocidal Active Substances in Alcohol-Based Hand Rubs
	19.4	 Overuse During the COVID-19 Pandemic
	19.5	 Non-biocidal Alternatives
	19.6	 Antiseptic Stewardship Implications
	References
20: Antiseptic Stewardship for Skin Antiseptics
	20.1	 Composition and Intended Use
	20.2	 Selection Pressure Associated with Commonly Used Biocidal Active Substances
		20.2.1	 Change of Susceptibility by Low-Level Exposure
		20.2.2	 Cross-Tolerance to Other Biocidal Active Substances
		20.2.3	 Efflux Pump Genes
		20.2.4	 Tolerance Gene Plasmids
		20.2.5	 Horizontal Gene Transfer
		20.2.6	 Viable but Not Culturable
		20.2.7	 Antibiotic Resistance Gene Expression
		20.2.8	 Other Risks Associated with Commonly Used Biocidal Active Substances
	20.3	 Effect on Biofilm
		20.3.1	 Biofilm Development
		20.3.2	 Biofilm Removal
		20.3.3	 Biofilm Fixation
	20.4	 Health Benefit of Commonly Used Biocidal Active Substances in Skin Antiseptics
	20.5	 Non-biocidal Alternatives
	20.6	 Antiseptic Stewardship Implications
	References
21: Antiseptic Stewardship for Surface Disinfectants
	21.1	 Composition and Intended Use
	21.2	 Selection Pressure Associated with Commonly Used Biocidal Active Substances
		21.2.1	 Change of Susceptibility by Low-Level Exposure
		21.2.2	 Cross-Tolerance to Other Biocidal Active Substances
		21.2.3	 Efflux Pump Genes
		21.2.4	 Tolerance Gene Plasmids
		21.2.5	 Horizontal Gene Transfer
		21.2.6	 Viable but Not Culturable
		21.2.7	 Other Risks Associated with Biocidal Active Substances in Surface Disinfectants
	21.3	 Effect of Commonly Used Biocidal Active Substances on Biofilm
		21.3.1	 Biofilm Development
		21.3.2	 Biofilm Removal
		21.3.3	 Biofilm Fixation
	21.4	 Health Benefits of Biocidal Active Substances in Surface Disinfectants
		21.4.1	 Floor Disinfection
		21.4.2	 Regular Patient Room Disinfection
		21.4.3	 Final Patient Room Disinfection
		21.4.4	 Ward Disinfection
	21.5	 COVID-19 Pandemic Overuse
	21.6	 Non-biocidal Alternatives
		21.6.1	 Probiotic Cleaners
		21.6.2	 Photodynamic Treatment
	21.7	 Antiseptic Stewardship Implications
	References
22: Antiseptic Stewardship for Instrument Disinfectants
	22.1	 Composition and Intended Use
	22.2	 Selection Pressure Associated with Commonly Used Biocidal Active Substances
		22.2.1	 Change of Susceptibility by Low-Level Exposure
		22.2.2	 Cross-Tolerance to Other Biocidal Active Substances
		22.2.3	 Efflux Pump Genes
		22.2.4	 Tolerance Gene Plasmids
		22.2.5	 Viable but Not Culturable
		22.2.6	 Other Risks Associated with Biocidal Agents in Instrument Disinfectants
	22.3	 Effect of Commonly Used Biocidal Active Substances on Biofilm
		22.3.1	 Biofilm Development
		22.3.2	 Biofilm Removal
		22.3.3	 Biofilm Fixation
	22.4	 Expected Health Benefit of Biocidal Active Substances in Instrument Disinfectants
	22.5	 Non-biocidal Alternatives
	22.6	 Antiseptic Stewardship Implications
	References
23: Antiseptic Stewardship for Antimicrobial Soaps
	23.1	 Composition and Intended Use
	23.2	 Selection Pressure Associated with Commonly Used Biocidal Active Substances
		23.2.1	 Change of Susceptibility by Low-Level Exposure
		23.2.2	 Cross-Tolerance to Other Biocidal Active Substances
		23.2.3	 Efflux Pump Genes
		23.2.4	 Tolerance Gene Plasmids
		23.2.5	 Horizontal Gene Transfer
		23.2.6	 Viable but Not Culturable
		23.2.7	 Antibiotic Resistance Gene Expression
		23.2.8	 Other Risks Associated with Biocidal Active Substances in Antimicrobial Soaps
	23.3	 Expected Health Benefit of Biocidal Active Substances in Antimicrobial Soaps
		23.3.1	 Antiseptic Body Wash Before Surgery
		23.3.2	 Antiseptic Body Wash for Patients on Intensive Care Units
		23.3.3	 Antiseptic Body Wash for Decolonisation of MRSA
		23.3.4	 Surgical Scrubbing
		23.3.5	 Hygienic Hand Wash
	23.4	 COVID-19 Pandemic Overuse
	23.5	 Non-biocidal Alternatives
	23.6	 Antiseptic Stewardship Implications
	References
24: Antiseptic Stewardship for Wound and Mucosal Antiseptics
	24.1	 Composition and Intended Use
	24.2	 Selection Pressure Associated with Commonly Used Biocidal Active Substances
		24.2.1	 Change of Susceptibility by Low-Level Exposure
		24.2.2	 Cross-Tolerance to Other Biocidal Active Substances
		24.2.3	 Efflux Pump Genes
		24.2.4	 Tolerance Gene Plasmids
		24.2.5	 Horizontal Gene Transfer
		24.2.6	 Viable but Not Culturable
		24.2.7	 Antibiotic Resistance Gene Expression
		24.2.8	 Other Risks Associated with Biocidal Active Substances in Wound and Mucosal Antiseptics
	24.3	 Effect of Commonly Used Biocidal Active Substances on Biofilm
		24.3.1	 Biofilm Development
		24.3.2	 Biofilm Removal
		24.3.3	 Biofilm Fixation
	24.4	 Health Benefits of Biocidal Active Substances in Wound and Mucous Membrane Antiseptics
	24.5	 Non-biocidal Alternatives
		24.5.1	 Cold Plasma
		24.5.2	 Honey
	24.6	 Antiseptic Stewardship Implications
	References