Logo of tcriskmanDove Medical PressSubscribeSubmit a ManuscriptSearchFollowDovepressTherapeutics and Clinical Risk Management
Ther Clin Risk Manag. 2005 Dec; 1(4): 307–320.
Published online 2005 Dec.
PMCID: PMC1661639

Antimicrobial biocides in the healthcare environment: efficacy, usage, policies, and perceived problems


Biocides are heavily used in the healthcare environment, mainly for the disinfection of surfaces, water, equipment, and antisepsis, but also for the sterilization of medical devices and preservation of pharmaceutical and medicinal products. The number of biocidal products for such usage continuously increases along with the number of applications, although some are prone to controversies. There are hundreds of products containing low concentrations of biocides, including various fabrics such as linen, curtains, mattresses, and mops that claim to help control infection, although evidence has not been evaluated in practice. Concurrently, the incidence of hospital-associated infections (HAIs) caused notably by bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) remains high. The intensive use of biocides is the subject of current debate. Some professionals would like to see an increase in their use throughout hospitals, whereas others call for a restriction in their usage to where the risk of pathogen transmission to patients is high. In addition, the possible linkage between biocide and antibiotic resistance in bacteria and the role of biocides in the emergence of such resistance has provided more controversies in their extensive and indiscriminate usage. When used appropriately, biocidal products have a very important role to play in the control of HAIs. This paper discusses the benefits and problems associated with the use of biocides in the healthcare environment and provides a constructive view on their overall usefulness in the hospital setting.

Keywords: biocides, efficacy, resistance, healthcare


Chemical biocides have been used for centuries, originally for food and water preservation, although there are early accounts of their use for wound management (Lister 1867; Craig 1986; Semmelweis 1995). A clear landmark in the use of biocides in the healthcare setting was the advent of antisepsis and the use of chlorine water in the early 19th century (Rotter 1998, 2001). The 20th century witnessed a tremendous increase in the number of active compounds being used for disinfection, sterilization, and preservation, with the development of cationic biocides such as biguanides and quaternary ammonium compounds (QACs), phenolics, aldehydes, and peroxygens (Russell 1999a). The same chemical agent can be used for different applications, the main difference being the concentration at which it is employed. For example, the biguanide chlorhexidine is used for surface disinfection at 0.5%–4% volume/volume (v/v), for antisepsis at 0.02%–4% v/v and for preservation at a concentration of 0.0025%–0.01% v/v. The concentration of a biocide within a formulation or product is of prime importance for its antimicrobial activity, although there needs to be a balance between efficacy (ie, destroying microorganisms) and toxicity. In hospital settings, 3 levels of disinfection are recognized (high-, intermediate-, and low-level) depending upon the risk of microbial survival and transmission to patients (Rutala and Weber 1999, 2001, 2004a, 2004b). Hospital disinfection policies have a major role to play in the control of hospital-associated infections (HAIs) (Rutala 1990, 2000; Rutala and Weber 1999, 2004a; Nelson 2003; Fraise 2004). The increased usage of products containing low concentrations of commonly used biocides, such as phenolics and cationic compounds, has raised some concerns (Levy 2001; Daschner and Schuster 2004) about their overall efficacy, but also about the possible emergence of microbial resistance. Indeed, there are now multiple laboratory reports about the emergence of bacterial resistance to biocides, often as a result of exposure to a lower (sublethal) concentration (Moken et al 1997; Tattawasart et al 1999a; Thomas et al 2000, 2005; Chuanchuen et al 2001; Russell 2002a, 2004a; Walsh et al 2003). The possible development of bacterial resistance (not only to biocides, but also to antibiotics), the benefit of biocide usage, and their possible role in the emergence of multidrug-resistant bacteria, add further questions to the extensive use of biocidal products (Levy 2000; Russell 1999b, 2000, 2002a; Russell and Maillard 2000; Schweizer 2001; Bloomfield 2002). The benefits and disadvantages of biocide usage in the healthcare environment need to be carefully considered.

Biocides usage and activity

Biocides – usage and policies

Biocides are used extensively in healthcare settings for different applications: the sterilization of medical devices; the disinfection of surfaces and water; skin antisepsis; and the preservation of various formulations. In addition, there are now numerous commercialized products containing low concentrations of biocides, the use of which is controversial. Some professionals believe that the indiscriminate usage of biocides in the healthcare environment may not be justified and is detrimental in the long term, for example, by promoting the emergence of bacterial resistance to specific antimicrobials (Russell et al 1999; Levy 2000, 2001; Russell 2000, 2002b; Russell and Maillard 2000; Schweizer 2001; Bloomfield 2002; Daschner and Schuster 2004). The indiscriminate use of disinfectants in the hospital environment is not a new problem as it was raised in the 1960s (Ayliffe et al 1969), but it remains a current issue. There are diverging opinions regarding the use of biocide formulations and products for noncritical surface disinfection. While some view such use as unnecessary (Fraise 2004), others support such a practice (Rutala and Weber 2004a). The use of biocidal products may be more appropriate only in specific situations where the risk of spreading HAIs is high (Bloomfield et al 2004; Russell 2004a). Some surfaces may only need cleaning and do not require chemical disinfection as they are rarely heavily contaminated (Table 1), whereas other medical articles need thorough cleaning with detergents and chemical disinfection, eg, wash boils, bedpans, urinal (Table 1). Thorough cleaning, washing, and drying have been shown to limit the risk of infection (Babb and Bradley 1995a). Flexible endoscopes are of particular interest, since they are now used for a wide range of diagnostic and therapeutic procedures. Gastrointestinal endoscopes and bronchoscopes are often grossly contaminated and require special sterilization regimens involving chemical disinfectants as these medical devices are often heat sensitive. Several biocides are used for the high-level disinfection of these devices in specially designed automated machines, which clean, disinfect, and rinse the lumens and external surfaces of the flexible endoscopes. The biocides of choice are glutaraldehyde and ortho-phthalaldehyde, peracetic acid, alcohol, peroxygen products, chlorine dioxide, and superoxidized water for the main ones (Babb and Bradley 1995b) (Table 2). Guidelines are available from professional societies regarding the appropriate immersion time and risk assessment (BSG 1998). Overall, the incidence of post-procedural infection appears low (Fraise 2004). There are some reports describing the washer-disinfectors as a source of instrument contamination when the concentration of the high-level disinfectant is too low (van Klingeren and Pullen 1993; Griffith et al 1997), or when biofilms are present (eg, following a lack of cleaning and maintenance) (Babb 1993; Pajkos et al 2004).

Table 1
Treatment of the hospital environment and equipment
Table 2
Principles of disinfection policies

The treatment of air is particularly challenging and is rarely considered necessary in hospitals, although the NHS Estates (1994) recommends good ventilation with filtered air for operating theatres, isolation rooms, and safety cabinets. In addition, prevention of airborne contaminants, particularly from the environment, is important through regular maintenance and use of biocidal treatment of static water, etc, for example to prevent the onset of Legionella (NHS Estates 1993; HSC 2000).

The principles of disinfection policy in healthcare facilities has been described in several reports, by Rutala (1990, 2000), Ayliffe et al (1993), and more recently by Fraise (1999, 2004). Disinfection policies should take into account the reasons and purposes for which disinfectants are used, the risk of infection from equipment, or the environment and implementations of such policies (Table 2) (Fraise 2004). The benefits of the introduction of comprehensive disinfection policies on the reduction of HAIs have been described (Makris et al 2000), although their implementation has sometimes been perceived as unsatisfactory (Cadwallader 1989; Kugel et al 2000; Sofou et al 2002). For example, infection control is an important element of safe dental practice. Chemical biocides together with detergents are used for the disinfection of surfaces (Molinari et al 1996) that can become contaminated with blood and saliva (McColl et al 1994), and for the disinfection of impressions, prosthetic, and orthodontic appliances. However, a recent survey showed that a large number of dental practices have no written policies on disinfection and sterilization procedures (Bagg et al 2001). The lack of standard infection control measures has been blamed for HAIs (Nelson 2003; Rutala and Weber 2004b; Takahashi et al 2004).

Biocides – alteration of activity

The activity of a biocide depends upon a number of factors (Table 3), some inherent to the biocide, some to microorganisms. Among microorganisms most resistant to biocidal exposure are bacterial spores, followed by mycobacteria, Gram-negative, Gram-positive, and fungal microorganisms. The sensitivity of viruses usually depends upon their structure, but notably also depends on whether they possess an envelope (Maillard 2004), enveloped viruses being more sensitive to disinfection (Maillard 2001). Although there are exceptions within this summarized classification (eg, some mycobacteria are relatively sensitive to disinfection), this attempt at distinguishing microorganisms according to their susceptibility to biocides gives useful information for the selection of an appropriate biocidal agent (Russell et al 1997). However, it is not always possible to predict which microorganisms will be present on certain surfaces, although the organic load or the extent of microbial contamination, and the presence or not of a biofilm, can be anticipated (Fraise 1999; Rutala and Weber 1999). An understanding of the factors affecting antimicrobial activity is essential to ensure that a biocidal product/formulation is used properly (Russell 2004b). As mentioned in the introduction, a biocide's concentration is probably the most important factor to affect antimicrobial activity (Table 3) (Russell and McDonnell 2000). Poor understanding of the concentration exponent can lead to microbial survival on surfaces, but also in products, and thus to infection or spoilage. Bacterial survival in biocidal formulations, notably containing QACs, has been described since the 1950s' and has been linked to inappropriate usage (Speller et al 1971; Prince and Ayliffe 1972; Ehrenkranz et al 1980; Kahan 1984), for example, a decrease in active concentration (van Klingeren et al 1993) or the incorporation of low concentrations in medical devices such as catheters (Stickler 1974; Stickler and Chawla 1988). Bacteria resistant to all known preservatives have also been reported (Chapman 1998; Chapman et al 1998). Exposure/treatment time is also essential. Standard efficacy tests often recommend a minimal contact time, such as 1 min for the testing of hygienic handwash (CEN 1997a) or 5 min for the testing of disinfectants and antiseptics (CEN 1997b). Decreasing exposure time is often associated with a decrease in activity, which is exemplified from kinetic inactivation studies (Tattawasart et al 1999b; Fraud et al 2001; Walsh et al 2003). Other important factors relate to the conditions in which a product is employed, mainly the presence of organic materials (which will inactivate certain biocides), or the concurrent use of a quenching agent, eg, combining a cationic agent with an anionic surfactant (Table 3) (Russell 2004b), or the use of emollient after hand washing (Walsh et al 1987; Benson et al 1990). On this latter point, information available on the effect of hand care product is sometimes contradictory. Indeed, Heeg (2001) reported that the use of hand care products did not affect the antimicrobial efficacy of hand rub formulations, although, in this case, a very limited number of products were tested. In addition, the effect of temperature on biocidal activity is important to understand in specific situations, for example, where biocidal efficacy relies upon a combination of chemical inactivation and elevated temperature (eg, certain sterilization process; automated washer-disinfector), or when a preservative-containing formulation is stored at a low temperature. Finally, pH might not be as important here as it will affect mainly the formulation (thus a concern for the manufacturer), but should not change drastically during use. It has to be noted that a change of pH can alter the biocide's ionization and hence its activity, the growth of the microorganisms, and its overall surface charge, eg, increasing pH enhances the activity of cationic biocides (Russell 2004b). Understanding these factors is essential and the appropriate training of end users, ie, nursing and domestic staff, is important to ensure that the efficacy of a biocidal product/formulation is maintained (Widmer and Dangel 2004).

Table 3
Factors influencing the antimicrobial activity of biocides

Problems associated with the use of biocides

The emergence of bacterial resistance to biocides and the possible linkage between biocide and antibiotic resistance is a major topic of discussion and concern. The emergence of bacterial resistance to biocides is not a new phenomenon and has been described since the 1950s, particularly with products containing a cationic biocide (Russell 2004a). More recently, the emergence of bacterial resistance to biocides to low (inhibitory) concentrations has been widely reported, mainly from laboratory studies, but also from environmental investigations.

Emergence of bacterial resistance – evidence from laboratory investigations

Investigating the possible emergence of bacterial resistance to various biocides is a topical subject and reports can easily be found in the literature, notably on the understanding of the basis of such resistance. Low to intermediate levels of resistance have been observed in most cases, although from time to time high-level resistance has been reported, eg, with the bisphenol triclosan (Sasatsu et al 1993; Heath et al 1998, 2000), or with the chemosterilant glutaraldehyde (Griffiths et al 1997; Manzoor et al 1999; Fraud et al 2001; Walsh et al 2001), and oxidizing agents (Dukan and Touati 1996).

There is now a better understanding of the overall mechanisms that enable bacteria to withstand exposure to low concentrations of a biocide (Table 4) (Poole 2002; Cloete 2003). As mentioned earlier, some microorganisms are better at surviving a biocidal treatment than others, primarily through their intrinsic properties and impermeability. The impermeability barrier, encountered in spores (Russell 1990; Russell et al 1997; Cloete 2003), but also in vegetative bacteria such as mycobacteria, and to some extent, Gram-negative bacteria, limits the amount of a biocide that penetrates within the cell (Denyer and Maillard 2002; Lambert 2002). The role of specific cell structure, such as lipopolysaccharides (LPS) in Gram-negative bacteria (Denyer and Maillard 2002) and the mycoylarabinogalactan layer in mycobacteria (Lambert 2002), in this resistance mechanism has been demonstrated by the use of permeabilizing agents such as ethylenediamine tetraacetic acid (EDTA) (Ayres et al 1998; McDonnell and Russell 1999; Denyer and Maillard 2002), or organic acids (Ayres et al 1993; 1998), and cell wall inhibitors such as ethambutol (Broadley et al 1995; Walsh et al 2001). The insusceptibility of Gram-negative bacteria to biocidal agents can be decreased further by a change in overall hydrophobicity (Tattawasart et al 1999a), outer membrane ultrastructure (Tattawasart et al 2000a, 2000b), protein content (Gandhi et al 1993; Brözel and Cloete 1994; Winder et al 2000), and fatty acid composition (Jones et al 1989; Méchin et al 1999; Guérin-Méchin et al 1999, 2000).

Table 4
Mechanisms conferring biocide resistance in bacteria

Bacteria are also able to decrease the intracellular concentration of toxic compounds by using a range of efflux pumps (Nikaido 1996; Paulsen et al 1996a; Levy 2002; McKeegan et al 2003), which can be divided into five main classes: the small multidrug resistance (SMR) family (now part of the drug/metabolite transporter [DMT] superfamily), the major facilitator superfamily (MFS), the ATP-binding cassette (ABC) family, the resistance-nodulation-division (RND) family and the multidrug and toxic compound extrusion (MATE) family (Brown et al 1999; Borges-Walmsley and Walmsley 2001; Poole 2001, 2002, 2004; McKeegan et al 2003). The involvement of multidrug efflux pumps in bacterial resistance to various compounds including QACs, phenolics, and intercalating agents has been widely reported (Tennent et al 1989; Littlejohn et al 1992; Lomovskaya and Lewis 1992; Leelaporn et al 1994; Heir et al 1995, 1999; Sundheim et al 1998), particularly in Staphylococcus aureus with identified pumps such as QacA-D (Rouche et al 1990; Littlejohn et al 1992), Smr (Lyon and Skurray 1987), QacG (Heir et al 1999), and QacH (Heir et al 1998) and in Gram-negative such as Pseudomonas aeruginosa, with MexAB-OprM, MexCD-OprJ, MexEFOprN, and MexJK (Schweizer 1998; Chuanchuen et al 2002; Morita et al 2003; Poole 2004) and Escherichia coli with AcrAB-TolC, AcrEF-TolC, and EmrE (Moken et al 1997; McMurry et al 1998a; Nishino and Yamagushi 2001; Poole 2004) (Table 4).

Another mechanism that can contribute to the reduction in the concentration of a toxic compound is degradation (Table 4). Degradation has been well described for metallic salts with an enzymatic reduction (Cloete 2003) and for aldehydes with the involvement of aldehydes dehydrogenase (Kummerle et al 1996). The degradation of phenols, such as triclosan, by environmental strains (Hundt et al 2000) has been reported, but there is little evidence that such degradation takes place in clinical isolates. In addition, some bacteria express enzymes such as catalases, superoxide dismutase, and alkyl hydroxyperoxidases to prevent and repair free radical-induced damage caused by oxidizing agents (Demple 1996).

Finally, although the modification of a target site is a well-known mechanism of bacterial resistance to antibiotics (Chopra et al 2002), it does not usually occur with biocide – with possibly one exception, the bisphenol triclosan. This phenolic compound has been shown to interact specifically with an enoyl-acyl reductase carrier protein (Heath et al 1999; Levy et al 1999, Roujeinikova et al 1999; Stewart et al 1999), the modification of which was associated with low-level bacterial resistance to this compound (McMurry et al 1999; Heath et al 2000; Parikh et al 2000). The inhibition of the fatty acid biosynthesis might be involved in the growth-inhibitory effect of triclosan, but other mechanisms were involved in its lethal activity (Gomez Escalada et al 2005).

Some of the mechanisms described above are intrinsic to the microorganisms; ie, a natural property. The acquisition of resistance is of notable concern since a previously sensitive microorganism can become insusceptible to a biocide (Russell 2002b) or a group of antimicrobials through, eg, the acquisition of multidrug resistant determinants (Lyon and Skurray 1987; Silver et al 1989; Kücken et al 2000; Bjorland et al 2001). Acquired resistance can arise through several processes, eg, mutations, the amplification of an endogenous chromosomal gene, and the acquisition of genetic determinants (Lyon and Skurray 1987; Paulsen et al 1993; Poole 2002).

Phenotypic variations resulting from biocidal exposure might lead to bacterial resistance (Chapman 2003) and this is now well supported by documented laboratory evidence. This is an issue since phenotypic alterations can lead to the emergence of resistance to several unrelated compounds in vitro (Walsh et al 2003; Thomas et al 2005). Phenotypic variation and antimicrobial resistance also concern bacterial biofilms, which are increasingly associated with bacterial contamination and infection, eg, implants, catheters, and other medical devices (Costerton and Lashen 1984; Costerton et al 1987; Salzman and Rubin 1995; Gilbert et al 2003; Pajkos et al 2004). Bacteria in biofilms have been shown to be more resistant to antimicrobials than their planktonic counterparts (Allison et al 2000). Resistance results from a multicomponent mechanism involving phenotypic adaptation following attachment to surfaces (Brown and Gilbert 1993; Ashby et al 1994; Das et al 1998), impairment of biocide penetration, and enzymatic inactivation (Sondossi et al 1985; Giwercman et al 1991; Huang et al 1995; Gilbert and Allison 1999), and the induction of multidrug resistance operons and efflux pumps (Maira-Litran et al 2000).

Emergence of bacterial resistance to biocides and antibiotics – evidence from laboratory investigations

While there is ample evidence from laboratory studies of bacterial adaptation to biocides, linkage to antibiotic resistance is not always clear cut (McMurry et al 1998a, 1999; Tattawasart et al 1999a; Thomas et al 2000; Winder et al 2000; Walsh et al 2003; Nomura et al 2004). Several laboratory investigations have explored a possible linkage between bacterial resistance to antibiotics and different biocides such as the bisphenol triclosan (Moken et al 1997; McMurry et al 1998a; Chuanchuen et al 2001; Cottell et al 2003), the biguanide chlorhexidine (Russell et al 1998; Tattawasart et al 1999a), and QACs (Akimitsu et al 1999; Walsh et al 2003). Similar mechanisms of resistance have been identified such as impermeability (Tattawasart et al 1999a), the induction of multidrug efflux pumps (Levy 1992; Moken et al 1997; Schweizer 1998; Zgurskaya and Nikaido 2000; Noguchi et al 2002), over expression of multigene components or operons (Levy 1992) such as mar (Moken et al 1997; McMurry et al 1998a), soxRS and oxyR (Dukan and Touati 1996; McMurry et al 1998a; Wang et al 2001), and the alteration of a target site (McMurry et al 1999).

Emergence of bacterial resistance – evidence from investigations in situ

It has been suggested that the use of biocide in healthcare environments leads to the emergence of antibiotic resistance in bacteria, although the evidence in situ is lacking overall (Russell 2002a) or does not support such a claim (Lambert 2004). Nevertheless, there have been a number of cases linking biocide usage and emerging antibiotic resistance. For example, the use of silver sulphadiazine for the treatment of burn infection was associated with sulphonamide resistance (Lowbury et al 1976; Bridges and Lowbury 1977). Likewise, the use of chlorhexidine scrub-based preoperative showers might be associated with the emergence of methicillin-resistant S. aureus (MRSA) (Newsom et al 1990). The use of the biguanide in catheters for long-term indwelling catheterization was linked to the emergence of Gram-negative bacteria with multiple antibiotic resistance (Stickler 1974; Stickler and Chawla 1988). The bisphenol triclosan has also been associated with such cross-resistance (Chuanchuen et al 2001; Levy 2001; Aiello et al 2004; Schmid and Kaplan 2004) although evidence in situ is scarce and recent field investigations failed to make such a link (Lear et al 2002; Sreenivasan and Gaffar 2002; Cole et al 2003; Lambert 2004). The heavy use of QACs has also been blamed for the dissemination of qac genes and the spread of efflux pumps (Paulsen et al 1996a, 1996b; Heir et al 1998, 1999; Mitchell et al 1998; Sundheim et al 1998), although further evidence is needed to confirm such a link (Russell 2002a).

Other considerations

Biocides are chemical agents that are usually toxic at relatively high concentration, not only for the end user, but also for the environment (Dettenkofer et al 2004). The toxicity of some biocides has been particularly well described, eg, the high-level disinfectant glutaraldehyde, the use of which has been associated with dermatitis and occupational asthma (Di Stephano et al 1999; Shaffer and Belsito 2000; Vyas et al 2000). Toxicity and irritation have also been reported with other biocides such as chlorhexidine (Waclawski et al 1989), povidone iodine (Waran and Munsick 1995), and other disinfectants and antiseptics (Sweetman 2002), although such incidence is infrequent (Rutala and Weber 2004a). Hypersensitivity and irritation caused by antiseptics might account for the low compliance in handwashing among healthcare workers (Pittet 2001). A recent study found that hospital staff using disinfectants might not appreciate the health risks associated with a product (Rideout et al 2005).

The future of biocides in the healthcare environment

There is no doubt that biocides will continue to play an important role in the prevention of infection in the healthcare environment, although some caution is needed as to their usage and the type of products that should contain antimicrobials. For disinfection and antisepsis purposes, chemical biocides are usually used at high concentrations, exceeding their bacterial minimum inhibitory concentrations many times to achieve a rapid kill. At such concentrations, a biocide will interact with multiple target sites (Maillard 2002), and the emergence of bacterial resistance is therefore unlikely.

The increased usage of biocide in formulations and products is probably driven by the impetus to control and reduce the spread of HAIs (Favero 2002), by an increase in public awareness for microbial infection and contamination, and hygiene (Aiello and Larson 2001; Bloomfield 2002; Favero 2002), and by strong and profitable commercial interests. The use of such products needs to be balanced between the clear benefit of controlling infection and the potential risk associated with usage, not only in terms of emerging microbial resistance, but also their toxicity and environmental pollution (Daschner and Dettenkofer 1997; Russell 2002b; Gilbert and McBain 2003; Bloomfield et al 2004; Dettenkofer et al 2004; Rutala and Weber 2004a). In this respect, the benefits of using biocides on noncritical surfaces to prevent the transmission of HAIs should be evaluated further (Bloomfield et al 2004). Assessing the role of biocides in controlling nosocomial infection or the value of a disinfection policy is difficult to evaluate in situ, although such information is valuable for the selection of the appropriate regimens (Fraise 2004). For example, a recent study showed that the use of alcohol hand gel reduced HAIs significantly (Zerr et al 2005). For a biocidal formulation/policy to be effective, (1) knowledge of the chemical biocide (ie, activity and limitation), (2) training of end users, and (3) compliance, are essential. It has to be noted that, when possible, physical processing, eg, heat sterilization, offers many advantages over chemical disinfection and should be the method of choice when appropriate (Fraise 2004). Some authors and institutions have advocated the rotation of biocidal formulations despite a lack of scientific evidence of the benefits of such practice (Murtough et al 2001). A clear understanding of the mechanisms of action, the factors affecting their activity, and the problems associated with specific practice is essential and may contribute to the improvement of a biocidal product, in terms of activity, but also usage. For example, improved compliance to hand hygiene in healthcare settings was observed with the introduction of hand rub and alcoholic rub products (Pittet 2001; Boyce and Pittet 2002).

Likewise, understanding of microbial survival to disinfection, limitation, and activity of “chemical sterilants” has led to the commercialization of formulations with improved efficacy for the high-level disinfection of heat-sensitive medical devices (Rutala and Weber 1999; Maillard 2002).

Finally, there have been some interesting developments in the use of biocides for the treatment and prevention of potential infections. In the dental field, light-activated biocides such as toluidine blue are being explored for the treatment of root canals (Walsh 2003; Wilson 2004). In the medical field, the incorporation of biocide combinations (eg, phenolics, metallic salts) into implants (Petratos et al 2002), and catheters (Hanazaki et al 1999), and other medical devices (Masse et al 2000; Jones et al 2003) is a fast advancing field of research, although biocide-containing medical devices may be of some concern (Masse et al 2000; Stickler 2002). Advances in polymer technology and biocidal research will undoubtedly contribute to the emergence of novel biocidal product or biocide-coated/containing medical devices with selected usage and improve efficacy.


The last 50 years have witnessed an important increase in the number of biocides and their usage in the healthcare environment. When used correctly (ie, compliance with disinfection/antisepsis regimens), biocides have an important role to play in controlling infection (Larson et al 2000; Russell 2002a). There is still some uncertainty as to the extent of their use in the healthcare environment. Should they be reserved for the disinfection of critical and semi-critical items/areas only, or should they be used also on noncritical devices/surfaces? Should the use of biocide-embedded products (eg, plastics, fabrics) be encouraged or banned? There is no doubt that the use of chemical biocides creates a selective pressure. However, it is yet unclear in practice whether such pressure favors the emergence of bacterial resistance. It is pertinent to note that the development of antibiotic resistance as a result of the selective pressure exerted by their intensive use, and sometimes misuse, is well documented (WHO 2000). Monitoring the susceptibility profile of hospital isolates to biocides might therefore be indicated. This would provide useful information as to whether bacterial survival in the healthcare setting following exposure to chemical biocides results from the bacterial resistance mechanisms (eg, biofilm persistence) or from disinfection failure following inappropriate usage. More research is needed to better assess the effect and efficacy of biocidal policies in practice.

This paper focused mainly on bacterial infection and did not expend on infection/contamination caused by other microorganisms such as viruses, fungi, and prions. Among these microorganisms, prions are the most resistant to biocides and when the presence of these agents is suspected, the use of single-use items is recommended. If this is not possible, special sterilization regimens should be employed (Taylor and Bell 1993; Taylor 2001; Fichet et al 2004; Rutala and Weber 2004b). Nonenveloped viruses might also be particularly resilient to disinfection (Maillard 2001, 2004), although the virucidal efficacy of biocides and biocidal policies in situ is poorly documented. Again, more investigation is needed to gain a better understanding of the survival capabilities of these microorganisms in the healthcare environment following disinfection.

Biocides are essential in preventing and controlling infections in the healthcare environment and the benefits from their usage currently outweigh possible disadvantages (Rutala and Weber 2004a). Disinfection of noncritical surfaces and items, and the usage of biocide-containing products, need to be reviewed, although the incorporation of biocides into medical devices to prevent bacterial infection is promising, if controlled and assessed appropriately.


  • Aiello AE, Larson EL. An analysis of 6 decades of hygiene-related advertising: 1940–2000. Am J Infect Control. 2001;29:383–8. [PubMed]
  • Aiello AE, Marshall B, Levy SB, et al. Relationship between triclosan and susceptibilities of bacteria isolated from hands in the community. Antimicrob Agents Chemother. 2004;48:2973–9. [PMC free article] [PubMed]
  • Akimitsu N, Hamamoto H, Inoue R, et al. Increase in resistance of methicillin-resistant Staphylococcus aureus to β-lactams caused by mutations conferring resistance to benzalkonium chloride, a disinfectant widely used in hospitals. Antimicrob Agents Chemother. 1999;43:3042–3. [PMC free article] [PubMed]
  • Allison DG, McBain AJ, Gilbert P. Biofilms: problems of control. In: Allison DG, Gilbert P, Lappin-Scott HM, Wilson M, editors. Community structure and co-operation in biofilms. Cambridge: Cambridge Univ Pr; 2000. p 309–27.
  • Ashby MJ, Neale JE, Knott SJ, et al. Effect of antibiotics on non-growing cells and biofilms of Escherichia coli. J Antimicrob Chemother. 1994;33:443–52. [PubMed]
  • Ayliffe GAJ, Brightwell KM, Collins BJ, et al. Varieties of aseptic practice in hospital wards. Lancet. 1969;ii:1117–20. [PubMed]
  • Ayliffe GAJ, Coates D, Hoffman PN. Chemical disinfection in hospitals. London: Public Health Laboratory Services; 1993.
  • Ayres HM, Furr JR, Russell AD. A rapid method of evaluating permeabilizing activity against Pseudomonas aeruginosa. Lett Appl Microbiol. 1993;17:149–51.
  • Ayres HM, Payne DN, Furr JR, et al. Use of the Malthus-AT system to assess the efficacy of permeabilizing agents on the activity of antimicrobial agents against Pseudomonas aeruginosa. Lett Appl Microbiol. 1998;26:422–6. [PubMed]
  • Babb JR. Disinfection and sterilization of endoscopes. Curr Opin Infect Dis. 1993;6:532–7.
  • Babb JR, Bradley CR. Endoscope decontamination: where do we go from here? J Hosp Infect. 1995a;30(Suppl):543–51. [PubMed]
  • Babb JR, Bradley CR. A review of glutaraldehyde alternatives. Br J Theat Nurs. 1995b;5:20–41. [PubMed]
  • Bagg J, Sweeney CP, Roy KM, et al. Cross infection control measures and the treatment of patient at risk of Creutzfeld-Jakob disease in UK general dental practices. Br Dent J. 2001;191:87–90. [PubMed]
  • Benson L, Leblanc D, Bush L, et al. The effect of surfactant systems and moisturizing products on the residual activity of a chlorhexidine gluconate handwash using a pigskin substrate. Infect Control Hosp Epidemiol. 1990;11:67–70. [PubMed]
  • Bjorland J, Sunde M, Waage S. Plasmid-borne smr gene causes resistance to quaternary ammonium compounds in bovine Staphylococcus aureus. J Clin Microbiol. 2001;39:3999–4004. [PMC free article] [PubMed]
  • Bloomfield SF. Significance of biocide usage and antimicrobial resistance in domiciliary environments. J Appl Microbiol. 2002;92(Suppl):144–57. [PubMed]
  • Bloomfield S, Beumer R, Exner M, et al. Disinfection and the prevention of infectious disease. Am J Infect Control. 2004;32:311–12. [PubMed]
  • Borges-Walmsley MI, Walmsley AR. The structure and function of drug pumps. Trends Microbiol. 2001;9:71–9. [PubMed]
  • Boyce JM, Pittet D. Guidelines for hand hygiene in health-care settings. Am J Infect Control. 2002;30(Suppl):41–6.
  • Bridges K, Lowbury EJL. Drug resistance in relation to use of silver sulphadiazine cream in burns unit. J Clin Pathol. 1977;31:160–4. [PMC free article] [PubMed]
  • [BSG] British Society for Gastroenterology Working Party. Cleaning and disinfection of equipment for gastrointestinal endoscopy. Gut. 1998;42:585–93. [PMC free article] [PubMed]
  • Broadley SJ, Jenkins PA, Furr JR, et al. Potentiation of the effects of chlorhexidine diacetate and cetylpyridinium chloride on mycobacteria by ethambutol. J Med Microbiol. 1995;43:458–60. [PubMed]
  • Brown MRW, Gilbert P. Sensitivity of biofilms to antimicrobial agents. J Appl Bacteriol. 1993;74(Suppl):87–97. [PubMed]
  • Brown MH, Paulsen IT, Skurray RA. The multidrug efflux protein NorM is a prototype of a new family of transporters. Mol Microbiol. 1999;31:393–5. [PubMed]
  • Brözel VS, Cloete TE. Resistance of Pseudomonas aeruginosa to isothiazolone. J Appl Bacteriol. 1994;76:576–82. [PubMed]
  • Cadawallader H. Setting the seal on standards. Nurs Times. 1989;85:71–2. [PubMed]
  • [CEN] Comité Européen de Normalisation, European Committee for Standardization. EN 1499 Chemical disinfectants and antiseptics – Hygienic handwash – Test method and requirements (phase 2, step 2) London: British Standard Institute; 1997a.
  • [CEN] Comité Européen de Normalisation, European Committee for Standardization. EN 1276 Chemical disinfectants and antiseptics – Quantitative suspension test for the evaluation of bactericidal activity of chemical disinfectants and antiseptics for use in food, industrial, domestic and institutional areas – Test method and requirements (phase 2, step 1) London: British Standard Institute; 1997b.
  • Chapman JS. Characterizing bacterial resistance to preservatives and disinfectants. Int Biodeterior Biodegrad. 1998;41:241–5.
  • Chapman JS. Disinfectant resistance mechanisms, cross-resistance, and co-resistance. Int Biodeterior Biodegrad. 2003;51:271–6.
  • Chapman JS, Diehl MA, Fearnside KB. Preservative tolerance and resistance. Int J Cosm Sci. 1998;20:31–9. [PubMed]
  • Chopra I, Hesse L, O'Neill AJ. Exploiting current understanding of antibiotic action for discovery of new drugs. J Appl Microbiol. 2002;92(Suppl):4–15. [PubMed]
  • Chuanchuen R, Beinlich K, Hoang TT, et al. Cross-resistance between triclosan and antibiotics in Pseudomonas aeruginosa is mediated by multidrug efflux pumps: exposure of a susceptible mutant strain to triclosan selects nxfB mutants overexpressing MexCD-OprJ. Antimicrob Agents Chemother. 2001;45:428–32. [PMC free article] [PubMed]
  • Chuanchuen R, Narasaki CT, Schweizer HP. The MexJK efflux pump of Pseudomonas aeruginosa requires OprM for antibiotic efflux but not for effect of triclosan. J bacteriol. 2002;184:5036–44. [PMC free article] [PubMed]
  • Cloete TE. Resistance mechanisms of bacteria to antimicrobial compounds. Int Biodeterior Biodegrad. 2003;51:277–82.
  • Cole EC, Addison RM, Rubino JR, et al. Investigation of antibiotic and antibacterial agent cross-resistance in target bacteria from homes of antibacterial product users and nonusers. J Appl Microbiol. 2003;95:664–76. [PubMed]
  • Costerton JW, Lashen ES. Influence of biofilm on efficacy of biocides on corrosion-causing bacteria. Mater Performance. 1984;23:13–17.
  • Costerton JW, Cheng KJ, Geesey GG, et al. Bacterial biofilms in nature and diseases. Annu Rev Microbiol. 1987;41:435–64. [PubMed]
  • Cottell A, Hanlon GW, Denyer SP, et al. Bacterial cross-resistance to antibiotics and biocides: a study of triclosan-resistant mutants [abstract] Washington DC USA: ASM, Q278; 2003.
  • Craig CP. Preparation for the skin for surgery. Today's OR Nurse. 1986;8:17–20. [PubMed]
  • Daschner F, Dettenkofer M. Protecting the patient and the environment: new aspects and challenges in hospital infection control. J Hosp Infect. 1997;36:7–15. [PubMed]
  • Daschner F, Schuster A. Disinfection and the prevention of infectious disease: no adverse effects? Am J Infect Control. 2004;32:224–5. [PubMed]
  • Das JR, Bhakoo M, Jones MV, et al. Changes in biocide susceptibility of Staphylococcus epidermidis and Escherichia coli cells associated with rapid attachment to plastic surfaces. J Appl Microbiol. 1998;84:852–9. [PubMed]
  • Demple B. Redox signaling and gene control in the Escherichia coli soxRS oxidative stress regulon – a review. Gene. 1996;179:53–7. [PubMed]
  • Denyer SP, Maillard JY. Cellular impermeability and uptake of biocides and antibiotics in Gram-negative bacteria. J Appl Microbiol. 2002;92(Suppl):35–45. [PubMed]
  • NHS Estates. Ventilation in healthcare premises Health Technical Memorandum HTM 2040. London: HMSO; 1994.
  • NHS Estates. The control of legionellae in healthcare premises – a code of practice Health Technical Memorandum HTM 2040. London: HMSO; 1993.
  • Dettenkofer M, Wenzler S, Amthor S, et al. Does disinfection of environmental surfaces influence nosocomial infection rates? A systematic review. Am J Infect Control. 2004;32:84–9. [PubMed]
  • Di Stephano F, Siriruttanapruk S, McCoach J, et al. Glutaraldehyde: an occupational health hazard in the hospital setting. Allergy. 1999;54:1105–9. [PubMed]
  • Dukan S, Touati D. Hypochlorous acid stress in Escherichia coli: resistance, DNA damage, and comparison with hydrogen peroxide stress. J Bacteriol. 1996;178:6145–50. [PMC free article] [PubMed]
  • Ehrenkranz NJ, Bolyard EA, Wiener M, et al. Antibiotic-sensitive Serratia marcescens infections complicating cardio-pulmonary operations: contaminated disinfectants as a reservoir. Lancet. 1980;ii:1289–92. [PubMed]
  • Favero MS. Products containing biocides: perceptions and realities. J Appl Microbiol. 2002;92(Suppl):72–7. [PubMed]
  • Fichet G, Duval C, Antloga K, Dehene C, et al. Novel methods for disinfection of prion-contaminated medical devices. Lancet. 2004;364:521–6. [PubMed]
  • Fraise AP. Choosing disinfectants. J Hosp Infect. 1999;43:255–64. [PubMed]
  • Fraise AP. Decontamination of the environment and medical equipment in hospitals. In: Fraise AP, Lambert PA, Maillard JY, editors. Principles and practice of disinfection, preservation and sterilization. 4. Oxford: Blackwell Sci; 2004. pp. 563–85.
  • Fraud S, Maillard JY, Russell AD. Comparison of the mycobactericidal activity of ortho-phthalaldehyde, glutaraldehyde and other dialdehydes by a quantitative suspension test. J Hosp Infect. 2001;48:214–21. [PubMed]
  • Gandhi PA, Sawant AD, Wilson LA, et al. Adaptation and growth of Serratia marcescens in contact lens disinfectant solution containing chlorhexidine gluconate. Appl Environ Microbiol. 1993;59:183–8. [PMC free article] [PubMed]
  • Gilbert P, Allison DG. Biofilms and their resistance towards antimicrobial agents. In: Newman HN, Wilson M, editors. Dental plaques revisited: Oral Biofilms in Health and Diseases. Cardiff: Bioline Pr; 1999. pp. 125–43.
  • Gilbert P, McBain AJ. Potential impact of increased use of biocides in consumer products on prevalence of antibiotic resistance. Clin Microbiol Rev. 2003;16:189–208. [PMC free article] [PubMed]
  • Gilbert P, McBain AJ, Rickard AH. Formation of microbial biofilm in hygienic situations: a problem of control. Int Biodeterior Biodegrad. 2003;51:245–8.
  • Giwercman B, Jensen ET, Hoiby N, et al. Induction of β-lactamase production in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother. 1991;35:1008–10. [PMC free article] [PubMed]
  • Gomez Escalada M, Harwood JL, Maillard JY, et al. Triclosan inhibition of fatty acid synthesis and its effect on growth of Escherichia coli and Pseudomonas aeruginosa. J Antimicrob Chemother. 2005;55:879–82. [PubMed]
  • Griffiths PA, Babb JR, Bradley CR, et al. Glutaraldehyde-resistant Mycobacterium chelonae from endoscope washer disinfectors. J Appl Microbiol. 1997;82:519–26. [PubMed]
  • Guérin-Méchin L, Dubois-Brissonnet F, Heyd B, et al. Specific variations of fatty acid composition of Pseudomonas aeruginosa ATCC 15442 induced by quaternary ammonium compounds and relation with resistance to bactericidal activity. J Appl Microbiol. 1999;87:735–42. [PubMed]
  • Guérin-Méchin L, Dubois-Brissonnet F, Heyd B, et al. Quaternary ammonium compounds stresses induce specific variations in fatty acid composition of Pseudomonas aeruginosa. Int J food Microbiol. 2000;55:157–9. [PubMed]
  • Hanazaki K, Shingu K, Adachi W, et al. Chlorhexidine dressing for reduction in microbial colonization of the skin with central venous catheters: a prospective randomized controlled trial. J Hosp Infect. 1999;42:165–7. [PubMed]
  • [HSC] Health and Safety Commission. The control of Legionella bacteria in water systems; approved code of practice and guidance. Sheffield: Health and Safety Executive; 2000. Legionnaire's disease.
  • Heath RJ, Yu YT, Shapiro MA, et al. Broad spectrum antimicrobial biocides target the FabI component of fatty acid synthesis. J Biol Chem. 1998;273:30316–20. [PubMed]
  • Heath RJ, Rubin JR, Holland DR, et al. Mechanism of triclosan inhibition of bacterial fatty acid synthesis. J Biol Chem. 1999;274:11110–14. [PubMed]
  • Heath RJ, Li J, Roland GE, et al. Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene. J Bio Chem. 2000;275:4654–9. [PubMed]
  • Heeg P. Does hand care ruin hand disinfection? J Hops Infect. 2001;48(Suppl):37–9. [PubMed]
  • Heir E, Sundheim G, Holck AL. Resistance to quaternary ammonium compounds in Staphylococcus spp isolated from the food industry and nucleotide sequence of the resistance plasmid pST827. J Appl Bacteriol. 1995;79:149–56. [PubMed]
  • Heir E, Sundheim G, Holck AL. The Staphylococcus qacH gene product: a new member of the SMR family encoding multidrug resistance. FEMS Microbiol Lett. 1998;163:49–56. [PubMed]
  • Heir E, Sundheim G, Holck AL. The qacG gene on plasmid pST94 confers resistance to quaternary ammonium compounds in staphylococci isolated from the food industry. J Appl Microbiol. 1999;86:378–88. [PubMed]
  • Huang CT, Yu FP, McFeters GA, et al. Nonuniform spatial patterns of respiratory activity within biofilms during disinfection. Appl Environ Microbiol. 1995;61:2252–6. [PMC free article] [PubMed]
  • Hundt K, Martin D, Hammer E, et al. Transformation of triclosan by Trametes versicolor and Pycnoporus cinnabarinus. Appl Environ Microbiol. 2000;66:4157–60. [PMC free article] [PubMed]
  • Jones MW, Herd TM, Christie HJ. Resistance of Pseudomonas aeruginosa to amphoteric and quaternary ammonium biocides. Microbios. 1989;58:49–61. [PubMed]
  • Jones DS, McMeel S, Adair CG, et al. Characterisation and evaluation of novel surfactant bacterial anti-adherent coatings for endotracheal tubes designed for the prevention of ventilator-associated pneumonia. J Pharm Pharmacol. 2003;55:43–52. [PubMed]
  • Kahan A. Is chlorhexidine an essential drug? Lancet. 1984;ii:759–60. [PubMed]
  • Kücken D, Feucht HH, Kaulfers PM. Association of qacE and qacEΔ1 with multiple resistance to antibiotics and antiseptics in clinical isolates of Gram-negative bacteria. FEMS Microbiol Lett. 2000;183:95–8. [PubMed]
  • Kugel G, Peery RD, Ferrari M, et al. Disinfection and communication practices: a survey of US dental laboratories. J Amer Dent Assoc. 2000;131:786–92. [PubMed]
  • Kummerle N, Feucht HH, Kaulfers PM. Plasmid-mediated formaldehyde resistance in Escherichia coli: characterization of resistance gene. Antimicrob Agents Chemother. 1996;40:2276–9. [PMC free article] [PubMed]
  • Lambert PA. Cellular impermeability and uptake of biocides and antibiotics in Gram-positive bacteria and mycobacteria. J Appl Microbiol. 2002;92(Suppl):46–54. [PubMed]
  • Lambert RJW. Comparative analysis of antibiotic and antimicrobial biocide susceptibility data in clinical isolates of methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa between 1989 and 2000. J Appl Microbiol. 2004;97:699–711. [PubMed]
  • Larson EL, Early E, Cloonan P, et al. An organizational climate intervention associated with increases handwashing and decreased nosocomial infections. Behav Med. 2000;29:14–22. [PubMed]
  • Lear CJ, Maillard JY, Dettmar PW, et al. Chloroxylenol- and triclosan-tolerant bacteria from industrial sources. J Ind Microbiol Biotechnol. 2002;29:238–42. [PubMed]
  • Leelaporn A, Paulsen IT, Tennent JM, et al. Multidrug resistance to antiseptics and disinfectants in coagulase-negative staphylococci. J Med Microbiol. 1994;40:214–20. [PubMed]
  • Levy SB. Active efflux mechanisms for antimicrobial resistance. Antimicrob Agents Chemother. 1992;36:695–703. [PMC free article] [PubMed]
  • Levy SB. Antibiotic and antiseptic resistance: impact on public health. Pediatr Infect Dis J. 2000;19(Suppl):120–2. [PubMed]
  • Levy SB. Antibacterial household products: cause for concern. Emerg Infect Dis. 2001;7:512–5. [PMC free article] [PubMed]
  • Levy SB. Active efflux, a common mechanism for biocide and antibiotic resistance. J Appl Microbiol. 2002;92(Suppl):65–71. [PubMed]
  • Levy CW, Roujeinikova A, Sedelnikova S, et al. Molecular basis of triclosan activity. Nature. 1999;398:383–4. [PubMed]
  • Lister J. The antiseptic system and a new method of treating compound fracture, abscess, etc. Lancet. 1867;1:326. 257, 387, 507.
  • Littlejohn TG, Paulsen IP, Gillespie M, et al. Substrate specificity and energetics of antiseptic and disinfectant resistance in Staphylococcus aureus. FEMS Microbiol Lett. 1992;95:259–66. [PubMed]
  • Lomovskaya O, Lewis K. emr, an Escherichia coli locus for multidrug resistance. Proc Natl Acad Sci U S A. 1992;89:8938–42. [PMC free article] [PubMed]
  • Lowbury EJL, Babb JR, Bridges K, et al. Topical chemoprophylaxis with silver sulphadiazine and silver nitrate chlorhexidine cream: emergence of sulphonamide-resistant Gram-negative bacilli. Br Med J. 1976;i:493–6. [PMC free article] [PubMed]
  • Lyon BR, Skurray RA. Antimicrobial resistance of Staphylococcus aureus: genetic basis. Microbiol Rev. 1987;51:88–134. [PMC free article] [PubMed]
  • McColl E, Bagg J, Winning S. The detection of blood and dental surgery surfaces and equipment following dental hygiene treatment. Br Dent J. 1994;176:65–7. [PubMed]
  • McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action and resistance. Clin Microbiol Rev. 1999;12:147–79. [PMC free article] [PubMed]
  • McKeegan KS, Borges-Walmsley MI, Walmsley AR. The structure and function of drug pumps: an update. Trends Microbiol. 2003;11:21–9. [PubMed]
  • McMurry LM, Oethinger M, Levy SB. Overexpression of marA, soxS, or acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli. FEMS Microbiol Lett. 1998a;166:305–9. [PubMed]
  • McMurry LM, Oethinger M, Levy SB. Triclosan targets lipid synthesis. Nature. 1998b;394:531–2. [PubMed]
  • McMurry LM, McDermott PF, Levy SB. Genetic evidence that InhA of Mycobacterium smegmatis is a target for triclosan. Antimicrob Agents Chemother. 1999;43:711–13. [PMC free article] [PubMed]
  • Maillard JY. Virus susceptibility to biocides: an understanding. Rev Med Microbiol. 2001;12:63–74.
  • Maillard JY. Antibacterial mechanisms of action of biocides. J Appl Microbiol. 2002;92(Suppl):16–27. [PubMed]
  • Maillard JY. Viricidal activity of biocides. In: Fraise AP, Lambert PA, Maillard JY, editors. Principles and practice of disinfection, preservation and sterilization. 4. Oxford: Blackwell Sci; 2004. pp. 272–323.
  • Maira-Litràn T, Allison DG, Gilbert P. An evaluation of the potential of the multiple antibiotic resistance operon (mar) and the multidrug efflux pump acrAB to moderate resistance towards ciprofloxacin in Escherichia coli biofilms. J Antimicrob Chemother. 2000;45:789–95. [PubMed]
  • Makris AT, Morgan L, Gaber DJ, et al. Effect of a comprehensive infection control program on the incidence of infections in long-term care facilities. Am J Infect Control. 2000;28:3–7. [PubMed]
  • Manzoor SE, Lambert PA, Griffiths PA, et al. Reduced glutaraldehyde susceptibility in Mycobacterium chelonae associated with altered cell wall polysaccharides. J Antimicrob Chemother. 1999;43:759–65. [PubMed]
  • Masse A, Bruno A, Bosetti M, et al. Prevention of pin track infection in external fixation with silver coated pins: Clinical and microbiological results. J Biomed Mater Res. 2000;53:600–4. [PubMed]
  • Méchin L, Dubois-Brissonnet F, Heyd B, et al. Adaptation of Pseudomonas aeruginosa ATCC 15442 to didecyldimethylammonium bromide induces changes in membrane fatty acid composition and in resistance of cells. J Appl Microbiol. 1999;86:859–66. [PubMed]
  • Mitchell BA, Brown MH, Skurray RA. QacA multidrug efflux pump from Staphylococcus aureus: comparative analysis of resistance to diamidines, biguanides and guanylhydrazones. Antimicrob Agents Chemother. 1998;42:475–7. [PMC free article] [PubMed]
  • Moken MC, McMurry LM, Levy SB. Selection of multiple-antibiotic-resistant (Mar) mutants of Escherichia coli by using the disinfectant pine oil: Roles of the mar and acrAB loci. Antimicrob Agents Chemother. 1997;41:2770–2. [PMC free article] [PubMed]
  • Molinari JA, Schaefer MA, Runnells RR. Chemical sterilization, disinfection and antisepsis. In: Cottone JA, Terezhalmy GT, Molinari JA, editors. Practical infection control in dentistry. 2. Baltimore, MD: Williams and Wilkins; 1996. pp. 161–75.
  • Morita Y, Murata T, Mima T, et al. Induction of mexCD-oprJ operon for a multidrug efflux pump by disinfectants in wild-type Pseudomonas aeruginosa PAO1. J Antimicrob Chemother. 2003;51:991–4. [PubMed]
  • Murtough SM, Hiom SJ, Palmer M, et al. Biocide rotation in the healthcare setting: is there a case for policy implementation? J Hosp Infect. 2001;48:1–6. [PubMed]
  • Nelson DB. Infection control during gastrointestinal endoscopy. J Lab Clin Med. 2003;141:159–67. [PubMed]
  • Newsom SWB, White R, Pascoe J. Action of teicoplanin on perioperative skin staphylococci. In: Gruneberg RN, editor. Teicoplanin-further European experience. London: Royal Soc Med; 1990. pp. 1–18.
  • Nikaido H. Multidrug efflux pumps of gram-negative bacteria. J Bacteriol. 1996;178:5853–59. [PMC free article] [PubMed]
  • Nishino K, Yamagushi A. Analysis of a complete library of putative drug transporter genes in Escherichia coli. J Bacteriol. 2001;183:5803–12. [PMC free article] [PubMed]
  • Noguchi N, Tamura M, Narui K, et al. Frequency and genetic characterization of multidrug-resistant mutants of Staphylococcus aureus after selection with individual antiseptics and fluoroquinolones. Biol Pharm Bull. 2002;25:1129–32. [PubMed]
  • Nomura K, Ogawa M, Miyamoto H, et al. Antibiotic susceptibility of glutaraldehyde tolerant Mycobacterium chelonae from bronchoscope washing machine. Am J Infect Control. 2004;32:185–8. [PubMed]
  • Pajkos A, Vickery K, Cossart Y. Is biofilm accumulation on endoscope tubing a contributor to the failure of cleaning and decontamination? J Hosp Infect. 2004;58:224–9. [PubMed]
  • Parikh SL, Xiao G, Tonge PJ. Inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis, by triclosan and isoniazid. Biochemistry. 2000;39:7645–50. [PubMed]
  • Paulsen IT, Littlejohn TG, Radstrom P, et al. The 3' conserved segment of integrons contains a gene associated with multidrug resistance to antiseptics and disinfectants. Antimicrob Agents Chemother. 1993;37:761–8. [PMC free article] [PubMed]
  • Paulsen IT, Brown MH, Skurray RA. Proton-dependent multidrug efflux systems. Microbiol Rev. 1996a;60:575–608. [PMC free article] [PubMed]
  • Paulsen IT, Skurray RA, Tam R, et al. The SMR family: a novel family of multidrug efflux proteins involved with the efflux of lipophilic drugs. Mol Microbiol. 1996b;19:1167–75. [PubMed]
  • Petratos PB, Chen J, Felsen D, et al. Local pharmaceutical release from a new hydrogel implant. J Surg Res. 2002;103:55–60. [PubMed]
  • Pittet D. Compliance with hand disinfection and its impact on hospital-acquired infections. J Hosp Infect. 2001;48(Suppl A):40–6. [PubMed]
  • Poole K. Multidrug resistance in Gram-negative bacteria. Curr Opin Microbiol. 2001;4:500–8. [PubMed]
  • Poole K. Mechanisms of bacterial biocide and antibiotic resistance. J Appl Microbiol. 2002;92(Suppl):55–64. [PubMed]
  • Poole K. Acquired resistance. In: Fraise AP, Lambert PA, Maillard JY, editors. Principles and practice of disinfection, preservation and sterilization. 4. Oxford: Blackwell Sci; 2004. pp. 170–83.
  • Prince J, Ayliffe GAJ. In-use testing of disinfectants in hospitals. J Clin Pathol. 1972;25:586–9. [PMC free article] [PubMed]
  • Rideout K, Teschke K, Dimich-Ward H, et al. Considering risks to healthcare workers from glutaraldehyde alternatives in high-level disinfection. J Hosp Infect. 2005;59:4–11. [PubMed]
  • Rotter ML. Semmelweis' sesquicentennial: a little-noted anniversary of handwashing. Curr Opin Infect Dis. 1998;11:457–60. [PubMed]
  • Rotter ML. Argument for alcoholic hand disinfection. J Hosp Infect. 2001;48(Suppl):4–8. [PubMed]
  • Rouche DA, Cram DS, Di Bernadino D, et al. Efflux-mediated antiseptic gene qacA in Staphylococcus aureus: common ancestry with tetracycline and sugar transport proteins. Mol Microbiol. 1990;4:2051–62. [PubMed]
  • Roujeinikova A, Levy CW, Rowsell S, et al. Crystallographic analysis of triclosan bound enoyl reductase. J Mol Biol. 1999;294:527–35. [PubMed]
  • Russell AD. Bacterial spores and chemical sporicidal agents. Clin Microbiol Rev. 1990;3:99–119. [PMC free article] [PubMed]
  • Russell AD. Types of antimicrobial agents. In: Russell AD, Hugo WB, Ayliffe GAJ, editors. Principles and practice of disinfection, preservation and sterilization. 3. Oxford: Blackwell Sci; 1999a. pp. 5–94.
  • Russell AD. Bacterial resistance to disinfectants: present knowledge and future problems. J Hosp Infect. 1999b;43(Suppl):57–68. [PubMed]
  • Russell AD. Do biocides select for antibiotic resistance? J Pharm Pharmacol. 2000;52:227–33. [PubMed]
  • Russell AD. Introduction of biocides into clinical practice and the impact on antibiotic-resistant bacteria. J Appl Microbiol. 2002a;92(Suppl):121–35. [PubMed]
  • Russell AD. Antibiotic and biocide resistance in bacteria: comments and conclusion. J Appl Microbiol. 2002b;92(Suppl):171–3. [PubMed]
  • Russell AD. Bacterial adaptation and resistance to antiseptics, disinfectants and preservatives is not a new phenomenon. J Hosp Infect. 2004a;57:97–104. [PubMed]
  • Russell AD. Factors influencing the efficacy of antimicrobial agents. In: Fraise AP, Lambert PA, Maillard JY, editors. Principles and practice of disinfection, preservation and sterilization. 4. Oxford: Blackwell Sci; 2004b. pp. 98–127.
  • Russell AD, McDonnell G. Concentration: a major factor in studying biocidal action. J Hosp Infect. 2000;44:1–3. [PubMed]
  • Russell AD, Maillard JY. Reaction and response: Is there a relationship between antibiotic resistance and resistance to antiseptics and disinfectants among hospital-acquired and community-acquired pathogens? Am J Infect Control. 2000;28:204–6.
  • Russell AD, Furr JR, Maillard JY. Microbial susceptibility and resistance to biocides: an understanding. ASM News. 1997;63:481–7.
  • Russell AD, Tattawasart U, Maillard JY, et al. Possible link between bacterial resistance and use of antibiotics and biocides. Antimicrob Agents Chemother. 1998;42:2151. [PMC free article] [PubMed]
  • Russell AD, Suller MT, Maillard JY. Do antiseptics and disinfectants select for antibiotic resistance? J Med Microbiol. 1999;48:613–15. [PubMed]
  • Rutala WA. APIC guideline for selection and use of disinfectants. Am J Infect Control. 1990;18:99–117. [PubMed]
  • Rutala WA. Principles and practice in the healthcare facilities. Wahington DC: Association for Professional in Infection Control and Epidemiology; 2000. Disinfection, sterilization and antisepsis.
  • Rutala WA, Weber DJ. Infection control: the role of disinfection and sterilization. J Hosp Infect. 1999;43(Suppl):43–55. [PubMed]
  • Rutala WA, Weber DJ. Surface disinfection: should we do it? J Hosp Infect. 2001;48(Suppl A):64–8. [PubMed]
  • Rutala WA, Weber DJ. The benefits of surface disinfection. Am J Infect Control. 2004a;32:226–31. [PubMed]
  • Rutala WA, Weber DJ. Disinfection and sterilization in healthcare facilities: what clinician need to know. Healthcare Epidemiol. 2004b;39:702–9. [PubMed]
  • Salzman MB, Rubin LG. Intravenous catheter-related infections. Adv Pediatr Infect Dis. 1995;10:37–8. [PubMed]
  • Sasatsu M, Shimizu K, Noguchi N, et al. Triclosan-resistant Staphylococcus aureus. Lancet. 1993;341:756. [PubMed]
  • Schmid MB, Kaplan N. Reduced triclosan susceptibility in methicillin-resistant Staphylococcus epidermidis. Antimicrob Agents Chemother. 2004;48:1397–9. [PMC free article] [PubMed]
  • Schweizer HP. Intrinsic resistance to inhibitors of fatty acid biosynthesis in Pseudomonas aeruginosa is due to efflux: application of a novel technique for generation of unmarked chromosomal mutations for the study of efflux systems. Antimicrob Agents Chemother. 1998;42:394–8. [PMC free article] [PubMed]
  • Schweizer HP. Triclosan: a widely used biocide and its link to antibiotics. FEMS Microbiol Lett. 2001;202:1–7. [PubMed]
  • Semmelweis IP. The etiology, concept and prevention of childbed fever 1861 [classical article] Am J Obstet Gynecol. 1995;172:236–7. [PubMed]
  • Shaffer MP, Belsito DV. Allergic contact dermatitis from glutaraldehyde. Contact Dermatit. 2000;43:150–6. [PubMed]
  • Silver S, Nucifora G, Chu L, et al. Bacterial ATPases – primary pumps for exploring toxic cations and anions. Trends Biochem Sci. 1989;14:76–80. [PubMed]
  • Sofou A, Larsen T, Fiehn NE, et al. Contamination level of alginate impressions arriving at dental laboratory. Clin Oral Invest. 2002;6:161–5. [PubMed]
  • Sondossi M, Rossmore HW, Wireman JW. Observation of resistance and cross–resistance to formaldehyde and a formaldehyde condensate biocide in Pseudomonas aeruginosa. Int Biodeterior Biodegrad. 1985;21:105–6.
  • Speller DCE, Stephens ME, Vinat A. Hospital infection by Pseudomonas cepacia. Lancet. 1971;i:798–9. [PubMed]
  • Sreenivasan P, Gaffar A. Antiplaque biocides and bacterial resistance: a review. J Clin Periodontol. 2002;29:965–74. [PubMed]
  • Stewart MJ, Parikh S, Xiao G, et al. Structural basis and mechanism of enoyl reductase inhibition by triclosan. J Mol Biol. 1999;290:859–65. [PubMed]
  • Stickler DJ. Chlorhexidine resistance in Proteus mirabilis. J Clin Pathol. 1974;27:284–7. [PMC free article] [PubMed]
  • Stickler DJ. Susceptibility of antibiotic-resistant Gram-negative bacteria to biocides: a perspective from the study of catheter biofilms. J Appl Bact. 2002;92(Suppl):163–70. [PubMed]
  • Stickler DJ, Chawla JC. Antiseptics and long-term bladder catheterization. J Hosp Infect. 1988;2:337–8.
  • Sundheim G, Langsrud S, Heir E, et al. Bacterial resistance to disinfectants containing quaternary ammonium compounds. Int Biodeterior Biodegrad. 1998;41:235–9.
  • Sweetman SC. The Martindale. London: Pharmaceutical Pr; 2002.
  • Takahashi H, Kramer MGH, Yasui Y, et al. Noscomial Serratia marcescens outbreak in Osaka, Japan, from 1999 to 2000. Infect Control Hosp Epidemiol. 2004;25:156–61. [PubMed]
  • Tattawasart U, Maillard JY, Furr JR, et al. Development of resistance to chlorhexidine diacetate and cetylpyridinium chloride in Pseudomonas stutzeri and changes in antibiotic susceptibility. J Hosp Infect. 1999a;42:219–29. [PubMed]
  • Tattawasart U, Maillard JY, Furr JR, et al. Comparative responses of Pseudomonas stutzeri and Pseudomonas aeruginosa to antibacterial agents. J Appl Microbiol. 1999b;87:323–31. [PubMed]
  • Tattawasart U, Maillard JY, Furr JR, et al. Cytological changes in chlorhexidine-resistant isolates of Pseudomonas stutzeri. J Antimicrob Chemother. 2000a;45:145–52. [PubMed]
  • Tattawasart U, Maillard JY, Furr JR, et al. Outer membrane changes in Pseudomonas stutzeri strains resistant to chlorhexidine diacetate and cetylpyridinium chloride. Int J Antimicrob Agents. 2000b;16:233–8. [PubMed]
  • Taylor DM. Resistance of transmissible spongiform encephalopathy agents to decontamination. Contrib Microbiol. 2001;7:58–67. [PubMed]
  • Taylor DM, Bell JE. Prevention of iatrogenic transmission of Creutzfeldt-Jakob disease. Lancet. 1993;341:1543–4. [PubMed]
  • Tennent JM, Lyon BR, Midgley M, et al. Physical and biochemical characterization of the qacA gene encoding antiseptic and disinfectant resistance in Staphylococcus aureus. J Gen Microbiol. 1989;135:1–10. [PubMed]
  • Thomas L, Maillard JY, Lambert RJW, et al. Development of resistance to chlorhexidine diacetate in Pseudomonas aeruginosa and the effect of ‘residual’ concentration. J Hosp Infect. 2000;46:297–303. [PubMed]
  • Thomas L, Russell AD, Maillard JY. Antimicrobial activity of chlorhexidine diacetate and benzalkonium chloride against Pseudomonas aeruginosa and its response to biocide residues. J Appl Microbiol. 2005;98:533–43. [PubMed]
  • Van Klingeren B, Pullen W. Glutaraldehyde resistant mycobacteria from endoscope washers. J Hosp Infect. 1993;25:147–9. [PubMed]
  • Vyas A, Pickering CAC, Oldham LA, et al. Survey of symptoms, respiratory function, and immunology and their relation to glutaraldehyde and other occupational exposure among endoscopy nursing employee. Occup Environ Med. 2000;57:752–9. [PMC free article] [PubMed]
  • Waclawski ER, McAlpine LG, Thomson NC. Occupational asthma in nurses caused by chlorhexidine and alcohol aerosols. Br Med J. 1989;298:929–30. [PMC free article] [PubMed]
  • Walsh LJ. The current status of laser applications in dentistry. Aust Dent J. 2003;48:146–55. [PubMed]
  • Walsh B, Blakemore PH, Drabu YJ. The effect of handcream on the antibacterial activity of chlorhexidine gluconate. J Hosp Infect. 1987;9:30–3. [PubMed]
  • Walsh SE, Maillard JY, Russell AD, et al. Possible mechanisms for the relative efficacies of ortho-phthalaldehyde and glutaraldehyde against glutaraldehyde-resistant Mycobacterium chelonae. J Appl Microbiol. 2001;91:80–92. [PubMed]
  • Walsh SE, Maillard JY, Russell AD, et al. Development of bacterial resistance to several biocides and effects on antibiotic susceptibility. J Hosp Infect. 2003;55:98–107. [PubMed]
  • Wang H, Dzink-Fox JL, Chen M, et al. Genetic characterization of high-level fluoroquinolone resistant clinical Escherichia coli strains from China: role of acrA mutations. Antimicrob Agents Chemother. 2001;45:1515–21. [PMC free article] [PubMed]
  • Waran KD, Munsick RA. Anaphylaxis from povidone-iodine. Lancet. 1995;345:1506. [PubMed]
  • WHO. World Health Organisation report on infectious diseases. Geneva: WHO; 2000. Overcoming antimicrobial resistance.
  • Widmer AF, Dangel M. Alcohol-based handrub: evaluation of technique and microbiological efficacy with international infection control professionals. Infect Control Hosp Epidemiol. 2004;25:207–9. [PubMed]
  • Wilson M. Lethal photosensitisation of oral bacteria and its potential application in the photodynamic therapy of oral infections. Photocop Photobio Sci. 2004;3:412–18. [PubMed]
  • Winder CL, Al-Adham IS, Abdel Malek SM, et al. Outer membrane protein shifts in biocide-resistant Pseudomonas aeruginosa PAO1. J Appl Microbiol. 2000;89:289–95. [PubMed]
  • Zerr DM, Garrison MM, Allpress AL, et al. Infection control policies and hospital-associated infections among surgical patients: variability and associations in a multicenter pediatric setting. Pediatrics. 2005;115:387–92. [PubMed]
  • Zgurskaya HI, Nikaido H. Multidrug resistance mechanisms: drug efflux across two membranes. Mol Microbiol. 2000;37:219–25. [PubMed]

Articles from Therapeutics and Clinical Risk Management are provided here courtesy of Dove Press
PubReader format: click here to try


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...