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Effects of Biocides on antibiotic resistance

2. What are the main uses of biocides?

  • 2.1 What are the main applications for biocides in health care?
  • 2.2 In which consumer products are biocides used?
  • 2.3 How are biocides used in the food industry?
  • 2.4 How are biocides used in animal husbandry and in products of animal origin?
  • 2.5 How are biocides used in water treatment and industrial applications?

2.1 What are the main applications for biocides in health care?

The SCENIHR opinion states:

3.3.1. Biocides in health care

The proper use of biocides is a cornerstone of any effective programme of prevention and control of health care-associated infections (HAIs) (Maillard 2005). According to CEN/TC 216 (CEN/TC 216 Chemical disinfectants and antiseptics) the term disinfection designates an operation aimed at preventing an infection, the term antisepsis should be used to indicate the treatment of an infection. Disinfectants are used in the decontamination process of patient-care devices, environmental surfaces and intact skin. Antiseptics are applied to non intact skin and mucosa.

3.3.1.1. Biocides (disinfectants) on medical devices and surfaces

Biocides used to control the growth of pathogenic microorganisms or to eliminate them from inanimate objects, surfaces or intact skin, are classified on the basis of the level of inactivation reached. Low-level disinfectants inactivate most vegetative bacteria, some fungi and some viruses (enveloped viruses); intermediate-level disinfectants inactivate vegetative bacteria, mycobacteria, most viruses and most fungi, but do not necessarily kill bacterial spores; high-level disinfectants inactivate all micro-organisms (vegetative bacteria, mycobacteria, fungi, enveloped and non-enveloped viruses) except large numbers of bacterial spores. High-level disinfectants can inactivate spores when applied with prolonged exposure times and are called chemical sterilants.

Table 3 shows the disinfectants that have been approved for use in health care settings by the US Food and Drug Administration (US-FDA) or registered by the US Environmental Protection Agency (US-EPA) (Rutala 1996, Rutala and Weber 2007, Weber and Rutala 2006).

Table 3: Biocides approved by US-FDA for health care settings, or registered by the US-EPA

In 1968, Spaulding devised a rational approach to disinfection and sterilisation of patient-care devices, which were divided into three categories taking into account the degree of infection risk involved in the use of each one: critical devices, semicritical devices, non critical devices (Spaulding 1968).

Critical devices penetrate sterile tissues, including sterile cavities and the vascular system (e.g. surgical instruments, needles, syringes, implantable devices, intravascular devices, cardiac and urinary catheters, arthroscopes and laparoscopes) and must be sterile at the time of use because any microbial contamination could result in pathogen transmission. The most efficient and reliable method of sterilisation is steam under pressure; however, if heat sensitive, the device must be treated with ethylene oxide (ETO) or hydrogen peroxide plasma, or by chemical sterilants. Due to the inherent limitations of using liquid chemical sterilants in a non-automated reprocessor, their use must be restricted to critical devices that are heat sensitive and incompatible with other sterilisation methods.

Semi-critical devices are those that come into contact with mucous membranes or non intact skin. Examples of semicritical devices are: respiratory therapy and anesthesia equipment, flexible endoscopes, laryngeal blades, esophageal manometry probes, vaginal and rectal probes, anorectal manometry catheters and nasal specula. Sterilisation is the preferred method in order to provide the widest margin of safety, even though a high level disinfection would provide a patient-safe device.

Non-critical devices are those that come into contact with intact skin or those items that do not make contact with the patient. Examples of non-critical devices are stethoscopes, bedpans, blood pressure cuffs, ECG cables and electrodes. There is generally little risk of transmitting infectious agents to patients by means of non-critical devices. Therefore, low-level disinfectants may be used to process them. Environmental surfaces are also included in this category. Biocides are commonly used to disinfect environmental surfaces and near-patient surfaces (e.g. floors, walls, tables, bedrails, screens etc.); however, the routine use of biocides to disinfect environmental surfaces is controversial (Allerberger et al. 2002, Boyce 2007, Dettenkoffer et al. 2004, Dharan et al. 1999, Rutala and Weber 2001, Rutala and Weber 2004.).

The role of environmental surfaces in spreading of HAIs has not been clearly established. Even though they do not come into contact with the patients, there is evidence that they may contribute to epidemic or endemic spread of epidemiologically important bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and Clostridium difficile by acting as a reservoir from which health care workers contaminate their hands (Hota 2004, Talon 1999). Targeted disinfection of certain environmental surfaces is recommended in some instances to prevent the spread of pathogenic bacteria; for example surfaces contaminated with blood, stool, urine, or other potentially contaminated material, or frequently touched surfaces in high risk wards (for example intensive care units).

Given the complex and multifactorial nature of HAIs, it is advisable to implement well-designed studies that systematically investigate the role of environmental surface disinfection in preventing HAIs, and to define bacteriological standards with which to assess surface hygiene in health care settings (Dancer 2004, Dettenkoffer et al. 2004, Griffith et al. 2000).

A number of manufacturers have now developed a range of surfaces containing biocides that have started to appear in health care settings. Such products include, for example, plastics, shower rails, curtains or trolleys. These surfaces are often based on the use of metallic ions such as silver ions. A number of recent studies have also been performed on the re-introduction of metallic surfaces, e.g. copper for door handles and objects that are frequently manipulated (Mehtar et al. 2008, Noyce et al. 2006, Santo et al. 2008, Weaver et al. 2008). While some studies showed an antimicrobial activity of copper surfaces, their actual impact is difficult to ascertain (Airey and Verran 2007) when compared to other currently used surfaces (mainly stainless steel).

Antimicrobial wipes are being used with an increasing frequency in the health care environment. The active ingredients providing antimicrobial efficacy vary largely depending on the content of detergents, natural products and biocides within commercially available wipes. While these wipes might be part of the disinfection regime in place, a recent study highlighted the problems associated with them, in particular with inappropriate usage, such as repeated use on several surfaces (Williams et al. 2008).

3.3.1.2. Biocides (disinfectants and antiseptics) used on skin and mucosa

Some biocides are used to reduce total micro-organism counts or to eliminate pathogenic bacteria on skin from patients and personnel. Antiseptics differ from disinfectants in that they are applied to non intact skin and mucosa. Table 4 shows the most commonly used skin disinfectants and antiseptics in health care settings. In some preparations, agents are combined.

Alcohols are the most frequently used antimicrobial components of handrubs (Kampf et al. 1999, Kampf et al. 2004, Kampf et al. 2008, Pittet et al. 2007). Alcohol-based handrubs are considered the most efficacious agents for reducing the number of bacteria on the hands of health care workers as a result of increased usage compliance and antimicrobial efficacy (Boyce and Pittet 2002). They are recommended for routine disinfection of hands for all clinical indications, except when hands are visibly soiled

Table 4: Commonly used skin disinfectants and antiseptics

Source & ©: SCENHIR,  Assessment of the Antibiotic Resistance Effects of Biocides (2009),
Section 3.3.1Biocides in health care, p. 19-22

2.2 In which consumer products are biocides used?

The SCENIHR opinion states:

3.3.2. Biocides in consumer products

3.2.2.1. General aspects

Many different preservatives/antimicrobial substances/biocides are used in building materials, consumer products (such as cosmetics, household cleaning products, disinfectants, wipes etc.), and in furniture, curtains and wall papers etc. in home settings. However, the regular use of personal hygiene products (e.g. cosmetics, wipes), cleaning products, laundry detergents, pet disinfectants and general disinfectants are the major sources of exposure to biocides in home settings. The increasing use of biocidal products has been acknowledged and discussed by the International Forum on Home Hygiene (IFH, 2003).

3.2.2.2. Cosmetics and personal care products

In the EU, the use of preservatives* or antimicrobials in cosmetics is regulated by the EU Directive 76/768/EEC (the so-called "Cosmetics Directive"). Fifty-seven chemicals listed in Annex VI of this Directive are permitted, with the restrictions laid down in the Annex, for the use as preservatives in cosmetic products. The function of these molecules in the cosmetics is the protection of the products from microbial degradation. Most of these substances are commonly used in the cosmetic products, but not all of them are included in Annex I of the Commission Regulation of 4 December 2007, listing the identified existing active substances for evaluation (Commission Regulation EC/1451/2007).

*[Preservatives are substances which may be added to cosmetic products for the primary purpose of inhibiting the growth of micro-organisms in such products. Other substances used in the formulation of cosmetic products may also have anti-microbial properties and thus help in the preservation of the products, as for instance, many essential oils and some alcohols.]

Besides the use of the 57 antimicrobial agents regulated as preservatives in cosmetic products by the Cosmetic Directive, many other antimicrobial agents are also used in cosmetic products. The purpose of these non-regulated antimicrobials in cosmetic products is not described.

3.3.2.3. Household products

Although biocidal products as defined by the Biocide Directive 98/8/EC are not commonly used in household products, the active ingredients of the biocidal products in categories 1-9 of the Directive are widely used in household products and other consumer products. Regular use of household products such as laundry detergents, cleaning products, pet disinfectants and general disinfectants are the major sources of exposure to biocides in home settings. Biocides present in these products may be from different chemical groups, but their mechanism of action may be similar (see section 3.5.2.1).

Biocides/antimicrobial agents used as preservatives in household cleaning products and laundry detergents may contain the same active ingredients as cosmetic products. However, the use of biocides/antimicrobial agents in household products is not regulated. Furthermore, certain biocides present as preservatives in diverse household products may also be present in household cleaning products, where they may serve as disinfectants.

Many of the ingredients used in detergent products, such as cationic surfactants, quaternary ammonium compounds and fragrances, possess antimicrobial properties. In a survey of industrial and institutional cleaning products in Denmark, only a limited number of biocides, besides antimicrobial surfactants and other ingredients, were found (Madsen et al. 2005). Cleaning product formulations for private homes may be similar to those used in industry and in public and private buildings.

Disinfectants in consumer products are used to control or to prevent growth of micro-organisms. There is a great diversity in use and application types for these products e.g. liquids, granulates, powders, tablets, gasses etc.

Recently, surfaces coated with biocides have also been developed. These biocide-treated surfaces include a variety of active ingredients such as triclosan and metallic ions (see also section 3.3.1.1).

3.3.2.4. Triclosan in consumer products and textiles

Triclosan is used in cosmetics, cleaning products, paint, textiles and plastic products. The Danish EPA performed a survey of the use of triclosan in Denmark for the period 2000-2005 (Borling et al. 2005). The survey showed that the amount of triclosan in products on the Danish market had decreased from approx. 3.9 to 1.8 tonnes corresponding to a reduction of 54% in the period 2000-2004. Cosmetics were the largest contributor to the amount of triclosan on the Danish market, as they constituted 99% of the total reported amount in the survey. The largest amount of triclosan in cosmetics was found in products for dental hygiene, including toothpaste. In this group, the amount had decreased by 37%. Deodorant was the group of cosmetics with the greatest decrease in amount of triclosan (79%). A recent survey revealed that 15% of the most commonly sold deodorants in the Danish market contained <0.3% triclosan (Rastogi et al. 2007).

Clothing articles are treated with antibacterial compounds to avoid mal-odour produced by decomposition of sweat. Only one report could be identified addressing actual occurrence. Seventeen products from the Danish retail market were analysed for the content of some selected antibacterial compounds: triclosan, dichlorophen, Kathon 893, hexachlorophen, triclocarban and Kathon CG. Five of the selected products were found to contain 0.0007% - 0.0195% triclosan. None of the other target substances could be detected in any of the investigated products (Rastogi et al. 2003)

Source & ©: SCENHIR,  Assessment of the Antibiotic Resistance Effects of Biocides (2009)
, Biocides in consumer products, p. 22-23

2.3 How are biocides used in the food industry?

The SCENIHR opinion states:

3.3.3. Biocides in food production

Biocides are widely used in the food industry for the disinfection of production plants and of food containers, the control of microbial growth in food and drinks, and the decontamination of carcasses.

3.3.3.1. Biocides as disinfectants

Disinfection is regarded as a crucial step in achieving a defined, desired hygiene status in food production and processing areas, and in food processing plants. A variety of biocides are commonly used for the disinfection of equipment, containers, surfaces or pipework associated with the production, transport and storage of food or drink (including drinking water).

Disinfectants intended for use in the food-processing industry are regulated within the scope of Directive 98/8/EC on the placing of biocidal products on the market.

The use of disinfectant in water quality intended for human consumption is regulated by the so-called Drinking Water Directive 98/83/EC. Biocides are used at the waterworks to maintain the microbiological quality of the water before and during its distribution, by sustaining the total counts of micro-organisms at an acceptable level and eliminating pathogenic micro-organisms.

For drinking water treatment, chlorine has been used worldwide for the past century for pre-chlorination at the point of entrance of raw water, disinfection and post-disinfection in the water distribution system. However, because of the formation of halogenated by-products, pre-chlorination is no longer recommended and other oxidising agents such as ozone or chlorine-dioxide are more commonly used for disinfection. In some countries, post-disinfection is always performed with chlorine or chloramines.

3.3.3.2. Biocides as food preservatives

Preservatives are substances which prolong the shelf-life of foodstuffs by protecting them against deterioration caused by micro-organisms. These compounds are considered food additives and are regulated by the Food Additives Directive 89/107/EEC. Their use in food must be explicitly authorised at European level and they must undergo a safety evaluation before authorisation for using the preservative as intended.

Source & ©: SCENHIR,  Assessment of the Antibiotic Resistance Effects of Biocides (2009),
Sections 3.3. Biocides in food production, p. 24

2.4 How are biocides used in animal husbandry and in products of animal origin?

The SCENIHR opinion states:

Proper cleaning and disinfection play a vital role in protecting food animals from endemic and zoonotic diseases, and thus indirectly protecting human health. It is impossible to give detailed accounts of all applications, but uses can essentially be divided into four broad categories:

  • Cleaning and disinfection of farm buildings, particularly between batches of animals.
  • Creating of barriers, such as in the use of foot dips outside animal houses and disinfecting vehicles and materials during outbreaks of infectious diseases.
  • Direct application to animal surfaces such as teat dips.
  • Preservation of specific products such as eggs or semen.

The use of biocides in animal husbandry follows the prerequisites set in the Biocides Directive 98/8/EC that also invite Member States to regulate the use of these agents. Consequently, some Member States have published lists of authorised substances which are not harmonised. At present, in the absence of a mandatory monitoring system, no exact data on the amounts of substances used can be obtained. Although it appears that only few disinfectant types are commonly used on a given farm, the same disinfectant brand may be used for extended periods of time (See Table 5).

Table 5: Major biocides used in veterinary medicine and animal husbandry

3.3.4.1. Biocides as feed preservatives

Biocides are used as animal feed preservatives, with the aim of protecting feed against deterioration caused by micro-organisms. In the EU, feed preservatives are included in the category "technological additives" of feed additives under the Regulation (EC) 1831/2003 on additives for use in animal nutrition. Their use in food must be explicitly authorised at European level. Before authorisation they must undergo a safety evaluation by EFSA. Most of the authorised products for this purpose are organic acids added to feed or silage, to reduce the total microbial count or to control undesirable spoilage microrganisms.

3.3.4.2. Biocides for specific applications

Biocides as teat dips: The udders of animals used for milk production may be contaminated with faecal and other materials. Therefore, prior to milking, udders are cleaned with water that may contain biocides, although this is less common.

More frequently, after the milking process, so-called teat dips are applied to protect the milk duct and the entire udder from invading pathogens. Various chemicals are used for this purpose including chloroisocyanurates, which are organic chloramines, bronopol, quaternary ammonium compounds and iodine-based compounds (see Table 6).

In a guidance document (Doc-Biocides-2002/01) BPD (Biocidal Products according to Directive 98/8/EC) are defined as products used on animal skin during milking, such as teat dips or udder cleaning products, and may be used only after authorisation or registration in accordance with the procedures laid down in Directive 98/8/EC. Where a medical claim is made, disinfectants shall be treated as veterinary medicinal products and shall only be used if authorised in accordance with the provisions of Directive 2001/82/EC on veterinary medicinal products.

Biocide use in fish farming: Under the prerequisites of Directive 98/8/EC a range of disinfectants are permitted for decontamination in fish farming, for example for fish eggs, ponds and equipment. These include iodophores, metallic salts, haloorganic compounds, aldehydes, hydrogen peroxide, quaternary ammonium compounds and antimicrobial dyes.

Table 6: Components of (udder) teat dips used (or having been used) in dairy animals

3.3.5. Biocides in foods of animal origin

Because the use of antibiotics in animal production may give rise to residues in edible tissues such as milk, meat and eggs, Regulation 2377/90/EC requires that all antimicrobials obtain a pre-marketing approval, including an assessment of residue formation and of the potential effects on the human gut flora (EMEA 1999).

The use of biocides for the decontamination of carcasses is considered as a hygiene measure under Regulation (EC) 853/2004 on specific hygiene rules for food of animal origin to remove surface bacterial contamination from products of animal origin, such as poultry carcasses. The use of these biocides must be authorised by the European Commission after a safety assessment performed by the European Food Safety Authority (EFSA). Following a request from the European Commission, the EFSA has examined several substances used elsewhere in the world to decontaminate poultry carcasses. This work has focused on four substances; chlorine dioxide, acidified sodium chlorite, trisodium phosphate and peroxyacids. In 2005, an opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food concluded that these substances would not pose a safety concern within the proposed conditions of use (EFSA, 2005). The EFSA’s BIOHAZ Panel was also asked to examine the efficacy of peroxyacids, the only type of substance whose efficacy has been assessed. Due to the lack of data, the BIOHAZ Panel was unable to conclude on whether this substance effectively killed or reduced pathogenic bacteria on poultry carcasses.

In 2008, the EFSA BIOHAZ Panel examined the possible development of antimicrobial resistance through the use of the same four substances to decontaminate poultry carcasses. This Panel concluded that no data exist to show that the use of these substances will lead to increased bacterial tolerance to these substances or increased resistance to other antimicrobial agents. However, some evidence indicates bacterial tolerance to other antimicrobial substances or biocides that were not the subject of this opinion (EFSA 2008a, EFSA 2008b).

The EFSA has now been asked by the Commission to produce technical guidance on monitoring and collecting data on antimicrobial resistance so that the uncertainties noted by the panel in its opinion on the four substances are addressed. The EFSA has proposed to examine this alongside safety and efficacy considerations, as data on antimicrobial resistance should not be assessed in isolation. The EFSA will work closely with the Community Reference Laboratory for Antimicrobial Resistance in developing its work (Information as cited on the EFSA website)

Source & ©: SCENHIR,  Assessment of the Antibiotic Resistance Effects of Biocides (2009),
Sections 3.4.Biocides in animal husbandry & 3.3.5. Biocides in food of animal origin, p. 24-28

2.5 How are biocides used in water treatment and industrial applications?

The SCENIHR opinion states:

3.3.6. Biocides in the environment

Biocides may be used for a variety of applications, including water treatment, wastewater treatment or industrial use. These applications are addressed by the Biocidal Products Directive 98/8/EC, but in the absence of reporting requirements, the quantities used for these different purposes remain unknown.

Many wastewater treatment plants, especially those in coastal regions, include a final step of disinfection with chlorine. However, this practice is being questioned more and more frequently because of the toxicity of by-products for the marine fauna and the elimination of non pathogenic bacterial indicators of faecal contamination, whilst more resistant viruses and protozoa survive and may cause outbreaks for swimmers or sea-food consumers.

Cooling towers are a new place for intensive use of disinfectants since the discovery of their role in the dissemination of contaminated aerosols (Legionella sp and legionellosis). Many disinfectants are now used in order to avoid contamination of the cooling fluid; their fate is aerosolization or elimination in the wastewater.

The use of biocides as antifouling agents in building materials, on antimicrobial surfaces, and in fuels and plastic materials is also gaining in importance, but the quantities used are unknown. It is important to note that an increasing number of uses are linked with nano-size particles of disinfectants (e.g. protection of the concrete facades against lichens and moulds) progressively released in the environment.

The development of antimicrobial surfaces using antimicrobial coating or impregnated surfaces is of great interest. Although there is an increasing number of companies developing such surfaces for a variety of industrial applications, most of these applications are aimed at the protection of the surfaces against environmental spoilage, especially against fungal micro-organisms. The use of biocides within these surfaces is for preservation of the product or the surfaces proper (e.g. caulk; wall paper, paint).

However, some surfaces will release a low concentration of a biocide and as such might contribute to a localised selective pressure. At present, surfaces that release biocides and the effect of localised selective pressure on the environmental microbial flora and on inhabitants exposed to biocide aerosols stemming from biocide impregnated surfaces has not been investigated. It is thus difficult at this stage to discern the impact of such surfaces in emerging resistance to biocides or antibiotics

Source & ©: SCENHIR,  Assessment of the Antibiotic Resistance Effects of Biocides (2009),
Section 3.3.6. Biocides in the environment, p. 28


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