BIOCIDE USAGE AND ANTIMICROBIAL
RESISTANCE IN HOME SETTINGS: AN UPDATE
A review by the International Scientific Forum on Home
Hygiene (IFH)
October 2003
The IFH Scientific Advisory Board
Dr Rijkelt Beumer
Laboratory of Food Microbiology, Department of Food Technology and Nutrition, Wageningen
University Research Centre, Wageningen, The Netherlands
Professor Sally F Bloomfield
International Hygiene Research and Liaison Manager, Unilever Research, Port Sunlight, UK and
Visiting Professor of Environmental Health, Division of Life Sciences, King’s College London, London,
UK
Professor Dr Martin Exner
Director, Hygiene-Institut, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany
Professor Gaetano M Fara
Director, Istituto di Igiene "G. Sanarelli", Università "La Sapienza" di Roma, Rome, Italy
Professor Kumar Jyoti Nath
Director-Professor, Environmental Sanitation and Health. All India Institute of Hygiene and Public
Health, Calcutta, India
Dr Elizabeth Scott
Consultant in Food and Environmental Hygiene, Newton, Massachusetts, USA
BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
Biocide usage and antimicrobial resistance in home settings: an update
Introduction
A range of events over the past few years has raised awareness of the importance of the
domestic setting in the chain of infection transmission through the community. Unfortunately
however at a time when there is need to re-emphasise the importance of infection prevention
through good hygiene, in the community as well as hospitals and other settings, a range of
other issues related to infectious disease and its prevention have been publicised through the
professional and lay press which, although they require serious consideration, have created a
dilemma in the mind of the public. Whilst on one hand, publicity about emergent pathogens,
antibiotic resistance, vaccination, food poisoning etc have increased concerns about how best
to protect our family from infection, on the other we are now told that too little exposure to
microbes could be weakening our immunity to infection and leaving us more exposed to
allergic diseases (Rook and Stanford 1998). In addition, although it is generally agreed that
the cause of antibiotic resistance in clinical practice is antibiotic overprescribing, some
scientists suggest that widespread use of biocides, particularly in consumer products, may be
a contributory factor (Levy 1998; Russell et al.1998, 1999a, Levy 2002). Most recently Aiello
and Larson (2003) have hypothesised that the emergence of individuals in the community
carrying antibiotic-resistant organisms in the absence of known risk factors might relate to the
increasing use of antibacterial product (in particular those containing triclosan) in the
community settings.
Although IFH shares the concerns about the recent proliferation "antibacterial cleaners", our
evaluation of the clinical and microbiological data suggests that there are times and places in
the home, as in hospitals, where the use of a chemical disinfectant containing a biocidal agent
is advisable. In giving this advice IFH was concerned as to whether there was any evidence
to show that use of antimicrobials might be contributing to antibiotic resistance. In view of
these concerns, IFH decided to undertake a review of the scientific data related to the possible
links between antibiotic and biocide resistance. From this review, which was published in
2000 (http://www.ifh-homehygiene.org/public/micro00.htm)1, IFH concluded that, although
some laboratory studies have demonstrated links between biocide and antibiotic resistance
there is currently no evidence that it is a significant factor in the development of antibiotic
resistance in clinical practice. It was agreed however that this aspect requires constant review.
In this paper we re-evaluate these conclusions in the light of new data which has become
available since the publication of our IFH review in 2002. This subject has also been recently
reviewed by Gilbert and McBain (2003).
Reduced susceptibility to biocides and antibiotic resistance
1
This paper was also published in German: Beumer, R., Bloomfield, S.F., Exner, M., Fara, G.M., Nath, K.J. and Scott, E.
(2000) Resistenz von Mikroorganismen gegen Biozide. A review by the International Scientific Forum on Home Hygiene
(IFH). Mhp-Verlag Wiesbaden, 2002.
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BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
When assessing the significance of antimicrobial resistance it is important to bear in mind that
the term ‘resistance’ is a relative word. The microbicidal action of biocides (as opposed to
antibiotics) results from their interaction with a number of distinct biochemical targets on or
in the cell. Susceptibility of different microbes to an agent can vary significantly and changes
in the most sensitive target can alter this sensitivity. The multiplicity of targets however
usually dictates against the development of resistance (i.e treatment failure) because the
concentrations used for hygiene applications are usually much higher than the minimum
biocidal concentration. Similarly, although changes in permeability mediated either by
envelope modification or by the expression of efflux pumps may reduce susceptibility,
indications are that this has little influence on the outcome of biocide treatment at use
concentrations. It has recently been proposed that long term exposure to biocides in
commercially available hygiene products inevitable expose environmental microbial
communities to sub-effective concentrations causing the emergence of resistant communities.
Such resistance might related to mutational changes in the sensitive target site or to regulatory
mutant which cause constitutive expression of efflux pumps. Although selection of
communities with these modifications is unlikely to influence the susceptibility to biocides,
changes in susceptibility to third party antibiotics can be postulated. This is particularly the
case where the target site is shared between the antibiotic and the biocide, or where the
induction of efflux is sufficient to confer clinical levels of antibiotic resistance.
The significant number of studies investigating the relationship between resistance to biocides
and antibiotics are reviewed in detail by McDonnell and Russell (1999), Beumer et al. (2000,
http://www.ifh-homehygiene.org/public/micro00.htm) and Gilbert and Mc Bain (2003).
Overall, these studies indicate no consistent pattern, the observations suggesting or refuting
such a link varying according to the nature of the biocide and the antibiotic, the conditions
under which the evaluation was carried out and the parameters assessed (MIC or bactericidal
effects). In many cases, there is no indication of whether susceptibility changes were stable
or reversible. In fact it would be unbelievable if links between biocide and antibiotic
resistance were not observed since changes in the outer layers of the cell, particularly of
Gram-negative species, are likely to affect resistance to both biocides and antibiotics. The
variable response suggests that there is no single underlying cause. In the following sections,
new data regarding the underlying mechanisms for which have been shown to be responsible
for links between biocide and antibiotic resistance are reviewed.
Biocide usage and antibiotic resistance.
Where simultaneous changes in susceptibility to antibiotics, and to the types of biocides used
as disinfectants and antiseptics, have been investigated, the resistance determinants mostly
involved are genes encoding for multidrug efflux pumps – either plasmid-borne in Grampositive species or chromosomally-encoded in Gram-negatives. Links could also arise where
a selective target site for biocides is shared by a therapeutic agent or agents. Since there are
fundamental differences between these aspects they need to be considered separately.
Chromosomally-encoded multidrug efflux pumps in Gram-negative bacteria
Experimental evidence shows that chromosomally-encoded multidrug efflux pumps, such as
the Mex pumps in Psedomonas aeruginosa and AcrAB in species such as Escherichia coli
and Salmonella, are key in defining the intrinsic susceptibility of Gram-negative bacteria to
both biocides and antibiotics, but also play a role in the development of multiresistance to
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BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
these agents. Upregulation of acrAB is largely but not exclusively controlled by the regulator
MarA. Phenotypic adaptation in response to environmental stimuli, or mutations that increase
expression of efflux genes or MarA result in elevated levels of resistance.
Both antibiotic exposure and exposure to biocides has been shown to be a factor in the
emergence of multidrug efflux mutants conferring reduced antibiotic susceptibility. Moken et
al. (1997) showed that E. coli mutants selected for reduced susceptibility to pine oil
disinfectant also show reduced susceptibility to multiple antibiotics including tetracycline,
chloramphenicol, ampicillin and nalidixic acid, which is mediated via the mar and acr
operons. Importantly, however, the level of antibiotic resistance which develops is relatively
low and unlikely to compromise effectiveness in clinical use.
In a recent study, Potenski et al. (2003) showed that mutants of Salmonella Enteritidis
selected following exposure to the sanitizer chlorine, and food preservatives sodium nitrite,
sodium benzoate and acetic acid showed reduced susceptibility to nalidixic acid,
ciprofloxacin, tetracycline and chloramphenicol. Complementation experiments showed that
mar mutation was responsible for this resistance. In general, the isolates exhibited a similar
level of increased antibiotic resistance to each antibiotic. Although clinical resistance was not
achieved (as was the case where the strain was exposed to tetracycline) the level of resistance
was increase up to fourfold. These studies are similar to those reported by McMurry et al.
(1998) who analysed 29 antibiotic resistant clinical E. coli isolates and found that 3 of these
showed reduced susceptibility to triclosan of which 2 were mar mutants. It was not known if
the antibiotic resistance was due to multidrug efflux, or whether the triclosan had selected for
the antibiotic resistance, or the antibiotic resistance had selected for the triclosan resistance.
In assessing the possible impact of biocide usage on efflux or mar-mediated antibiotic
resistance it is important that it is considered in relation to other inimical agents which can
elicit this effect. Miller and Sulavick (1996) review studies showing that MarRAB responds
to a range of inducers reflecting a range of environmental conditions including the weak acid
salicylate. Since tetracycline and chloramphenicol are less effective than salicylate (albeit at
higher concentrations) in mar upregulation this suggests that salicylate is a ‘normal’ substrate
for this pump. From their review, Miller and Sulavick (1996) suggest that the wide substrate
specificity of these pumps and, for the AcrAB pump, regulation by global stress signals rather
than specific substrates, make them well suited for a general defensive role. If efflux pumps
evolved as a defence against antimicrobial agents occurring in the environment then it is to be
expected that a wide range of ‘natural’ antimicrobial agents, including materials such as pine
oils would produce these effects. In line with this Whyte et al. (2001) and Rickard et al (in
press) have shown that a significant proportion of a wide range of food household and
personal products acted as inducers of mar and acr when tested against lacz fusions of E. coli.
This included food substances such as mustard, chilli and garlic, and household products,
none of which made hygiene claims.
The mar locus is widespread amongst bacterial species and has been shown to regulate up to
60 chromosomal genes. The marRAB regulon is induced by the positive regulator SoxS that
is produced by transcription of soxRS in response to exposure to free radicals. It has been
postulated (Dodd et al. 1998; Bloomfield et al.1998) that if bacterial cells are growth-arrested
by treatment with an inimical agent, the imbalance between anabolism and catabolism causes
a burst of free radical production. If this hypothesis is correct it is possible that any chemical
4
BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
substance which produces a sudden decrease in growth rate including agents such as chlorine
could cause increased expression of acr multidrug efflux pumps.
Miller and Sulavick (1996) suggest that, although the wide substrate specificity of efflux
pumps may make them well suited for a defensive role, it also means that cells may also
pump out key metabolites making them relatively less competitive in mixed microbial
communities. Thus it is likely (as suggested in recent studies by Gilbert to be discussed later
in this paper) that, if the primary function is to facilitate continuous ‘modulation’ of efflux
activity in response to their ever-changing environment, mutant populations which express
efflux systems constitutively will decline in favour of wild type populations when the
selective pressure is removed, although Levy (2000) suggests that this may not be the case.
Plasmid-mediated efflux mechanisms in Gram-positive species
Plasmid-mediated antibiotic resistance in Gram-positive bacteria is well established as a
significant clinical problem. Since resistance to some biocides is also plasmid-mediated this
raises concern that biocide exposure could contribute to spread of antibiotic resistance by
selection and dispersal of plasmids producing resistance to both antibiotics and biocides. This
could be a plasmid bearing a resistance determinant for a common target site shared by the
antibiotic and one or more biocides or a biocide resistance determinant alongside structurally
unrelated determinants for antibiotic resistance e.g., penicillin-binding proteins.
For staphylococci, reduced biocide susceptibility is commonly associated with plasmidencoded efflux proteins. Studies of Staphylococcus aureus strains show that qacA, B, C and
D genes encoding multidrug efflux in conjunction with antibiotic resistance determinants on
multiresistance plasmids, are widely distributed in clinical and food isolates of Staph. aureus
and are associated with reduced susceptibility (assessed by MICs) to biocides such as
acriflavine, cetrimide, benzalkonium chloride (BAC) and chlorhexidine. Of concern is the
finding that the qacA/B family of genes show significant homology to other energy-dependant
transporters such as tetracycline transporters found in tetracycline-resistant strains, whilst
qacA/B can be borne on penicillinase plasmids (Rouche et al. 1990; Russell et al. 1999a).
In a recent study by Sidhu et al (2001) quaternary ammonium compound (QAC)-resistant
coagulase negative staphlyococci isolated from food and food processing industries were
investigated for the presence of genetic determinants (qacA/B and qacS/smr) encoding the
resistance to the QAC, benzalkonium chloride and antibiotic resistance genes. Six qacA/Bharbouring strains were also found to harbour the B-lactamase gene blaZ. In three of these
strains the gene were located on the same plasmid.
Studies involving biocides with specific target sites
As stated previously, many or most biocides attack several targets with differing
susceptibilities depending on concentration. Although, under use conditions, bactericidal
effects at higher concentrations may result from generalised cell disruption, growth inhibition
at lower concentrations may occur through interaction with specific target sites. Where such
sites are shared by a therapeutic agent then selection of a population bearing that target site by
exposure to low level biocide, would have no effect on susceptibility to the biocide but could
render the population clinically resistant to the therapeutic agent. Also of concern is the
possibility (but no evidence) that, if the resistance determinants were transferred to plasmids
also bearing determinants for one or unrelated targets conferring antibiotic resistance e.g.,
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BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
penicillin binding proteins, then persistent low-level biocide exposure could select for
antibiotic populations through selective pressure and plasmid transfer.
Studies, as previously reviewed, showed that sublethal levels of triclosan select for mutants
in the fabI gene of E. coli. FabI encodes the enoyl reductase enzyme, an essential enzyme
involved in the synthesis of fatty acids. Triclosan shares this target with some therapeutic
agents and as such could at sublethal concentrations select for resistance to third party
antimicrobials. Reductions in the isoniazid sensitivity of Mycobacterium smegmatis can be
conferred by mutation in inha which is a homologue of FabI. (McMurry et al. 1999).
However similar phenomena have not been demonstrated for Mycobacterium tuberculosis
which remains sensitive to triclosan (Parikh et al 2000, Slayden et al 2000). This suggests
that although the 2 agents share the same target, their interactions with it are not the same.
Other studies suggesting the possibility of shared target sites are described in our earlier IFH
review of biocides and resistance.
Biocide and antibiotic resistance in environmental and clinical settings
Although the laboratory data suggests that some types of biocides do have the potential to
encourage the emergence of antibiotic-resistance within microbial populations, either by
selection of a multidrug resistant population or by transfer of multiresistant plasmids, the key
question is whether and to what extent these mechanisms might operate in natural and clinical
environments. In assessing the practical implications of the laboratory-based data, three
criteria need to be assessed, firstly whether the level of antibiotic insusceptibility is sufficient
to compromise the clinical response, secondly how extensively these mechanisms might occur
in the environment or in clinical practice, and thirdly whether and to what extent theses
resistant populations have the ability to compete and persist in the natural environment.
Current evidence suggests that for Gram-negative multidrug efflux pumps, the level of
antibiotic resistance induced or acquired through biocide exposure is relatively low and
unlikely to compromise clinical effectiveness. The significance of multiresistant plasmid
transfer in Gram-positive species, particularly in Staphylococcus species, still requires further
investigation as does the possibility of mutation in shared target sites in Gram-negative and
Gram-positive species. Although biocides are normally used at concentrations which are
rapidly bactericidal, in any environment (or downstream of that environment) there is likely to
be a continuum of biocide concentration ranging from treatment concentration to nil.
Theoretically, sub-lethal concentrations of biocide for any given cellular target will occur at
some point along this concentration gradient, providing a selection pressure for mutations in a
multiplicity of cellular targets. Biofilm communities also provide highly selective
environments where sharp gradients of antimicrobial agents will prevail and selective
pressures will be greatest (Gilbert et al 2002).
If acquisition of multi-target plasmids encoding reduced biocide susceptibility alongside
antibiotic resistance is a real possibility, it is interesting to speculate to what extent this might
occur outside the hospital environment. Logically the sequential addition of antibiotic
resistance determinants onto plasmids conferring reduced susceptibility to biocides should
only occur where bacterial populations are exposed to persistent low level of biocides and
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BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
also regularly subjected to the selective pressure from antibiotics. A number of studies have
been recently reported which assess the prevalence of antibiotic resistant strains in community
environments. Rutala et al. (2000) found that the frequency occurrence of antibiotic resistance
in environmental isolates from homes was much lower than for clinical isolates from a
hospital intensive care unit and an outpatient setting. A few isolates of Enterococcus and
Enterobacter showed resistance to vancomycin and cefotaxime respectively, but no evidence
of resistance was seen in isolates of Staph. aureus, Ps. aeruginosa, E.coli or Klebsiella
pneumoniae. These results are in line with 2 further studies which investigated whether
antibiotic resistant strains of bacteria were more likely to be found in domestic homes where
antibacterial products were used compared with homes where they were not used (Marshall et
al. 2003, Cole et al. 2003). Samples were collected from houses in the USA and UK of 30
users and nonusers of antibacterials. Susceptibility tests against antibiotics and antibacterial
agents (triclosan, pine oil, BAC and para-chloro-meta-xylenol) were carried out on the
bacteria isolated. The authors conclude that there was no evidence that antibiotic resistant
strains occurred more frequently in user homes compared with non-user homes.
An important aspect to consider is that, if the selection of mutants which are co-resistant to
biocides and antibiotics through shared targets depends on the existence of specific biocide
targets, it is unlikely (although not impossible) to apply to chemically-reactive agents such as
chlorine or oxygen-releasing agents, or solvent molecules such as alcohols. This likelihood is
further reduced by the fact that these agents are unstable or volatile and thus do not persist in
the environment in an active form.
A further aspect which has recently been investigated by Gilbert and co-workers is the
“fitness” of resistant microbial clones resulting from exposure of naturally-occuring
communities (which are inevitably mixed communities) to sublethal levels of biocides.
Where a pathogen infects the body it has only to compete with host defences. In the general
and domestic environment, bacteria have to survive in communities which are highly
competitive, in which compromised strains will be rapidly replaced by more competent flora.
To proliferate within a community of different species, a newly selected clone should
demonstrate enhanced fitness. Many studies have show that development of antimicrobial
resistance is associated with decreased fitness of the organism. Considering the prevalence of
naturally resistant species, Gilbert has postulated that, rather than selection of resistant
mutants, exposure to sublethal levels of biocides is more likely to cause clonal expansion or
pre-existing resistant species. In this respect many biofilm communities are dominated by
species which are refractory to a wide range of antimicrobial compounds. To investigate this
possibility Gilbert and co-workers (McBain et al 2003a) have examined the effects of
exposure of sink drain microcosms to triclosan. A long-term microcosm was stabilized for 6
months before being subjected to successive 3-month exposures to triclosan at sublethal
concentrations. Culturable bacteria were identified and their susceptibilities to four biocides
and six antibiotics were determined. Viable cell counts were largely unaffected by triclosan
exposure, but species diversity was decreased. Triclosan susceptibilities ranged widely within
bacterial groups, and triclosan-tolerant strains (including aeromonads, pseudomonads,
stenotrophomonads, and Alcaligenes spp.) were isolated before and after triclosan exposure.
Several triclosan-tolerant bacteria related to Achromobacter xylosoxidans became clonally
expanded during dosing. Triclosan addition did not significantly affect the community
profiles of susceptibility to the test biocides or antibiotics. It was also found that triclosan is
degradable by common domestic biofilms. In a second study McBain et al (2003b)
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BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
investigated the effects of prolonged exposure of in vitro oral bacterial ecosystem within a
constant-depth film fermenter to a chlorhexidine gluconate-containing mouthwash (CHXM).
Results showed that CHXM exposure caused considerable decreases in microbial diversity.
Pure-culture studies of 10 oral bacteria showed that Actinomyces naeslundii, Veillonella
dispar, Prevotella nigrescens, and the streptococci were highly susceptible to CHX, while
Lactobacillus rhamnosus, Fusobacterium nucleatum, and Neisseria subflava were the least
susceptible. Determination of the MICs of triclosan, CHX, erythromycin, penicillin V,
vancomycin, and metronidazole for microcosm isolates, before and after 5 days of CHXM
exposure, showed that CHXM exposure altered the distribution of isolates toward those that
were less susceptible to CHX. Changes in susceptibility distributions for the other test agents
were not statistically significant. A similar pattern was observed for exposure of an in vitro
plaque ecosystem exposed to a triclosan-containing mouthwash (McBain et al 2003c).
These results are in line with earlier studies such as those of Armstrong et al. (1982) and
Murray et al (1984) who reported that chlorination of sewage and of water supplies altered the
distribution of isolates producing an increased proportion of species which showed reduced
susceptibility to some (but not all) of a range of antibiotics which were tested. The concern
must be as to whether the selective pressure from biocide exposure might select for species
which are not only more resistant to antimicrobials, but also pathogenic. Gilbert and McBain
(2002) conclude that the available data indicates that organisms such as environmental
pseudomonads which are intrinsically resistant to all but the strongest oxidising biocides
frequently benefit from biocidal treatments by clonal expansion into ecological niches
previously occupied by more sensitive species, but in general these organisms are relatively
benign. Murray et al, on the other hand expressed concern that some fo the species which
they isolated from chlorinated sewage samples were potentially pathogenic.
Also of concern, as reviewed by Aiello and Larson (2003), is the emergence of individuals in
the community carrying antibiotic-resistant organisms in the absence of known risk factors.
One of the observation which led Aiello and Larson to hypothesise that this might relate to the
increasing use of antibacterial products in the community settings was that the observation
that some community-acquired MRSA strains (c-MRSA) show an antibiotic susceptibility
profile which is markedly different from hospital-acquired MRSA; cMRSA strains are chiefly
resistant to B-lactams antibiotics (penicillins and cephalosporins). In line with this Akimitsu
et al. (1999) showed that selection of MRSA with decreased susceptibility to BAC produced
strains which were cross resistant to a variety of B-lactam antibiotics but not to other
antibiotics. Levy (2001) noted that exclusive resistance to B-lactam antibiotics among MRSA
isolates with decrease susceptibility to BAC matches the susceptibility of some c-MRSA
isolates. This correlates with a report of 4 cases in different geographical, locations where
children whose resistance was limited to lactam antibiotics died with MRSA (Anon 1999b).
Aiello and Larson conclude however that much further research is necessary to examine these
and other factors originating from the community setting that may have impact on antibiotic
resistance.
Conclusions
The conclusion of the IFH (as also concluded by other reviewers (Russell et al. 1999a;
Russell 2000; Gilbert and McBain 2003; Aiello and Larsen 2003) remains, namely that there
is no equivocal evidence that biocide usage contributes to the development of antibiotic
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BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
resistance either in clinical practice or in the general environment; antibioitc use is currently
assumed to be the major cause of antibiotic resistance in clinical practice. There is agreement
however that, since significant questions remain unanswered however, it is vitally important
that we continue to research and monitor the situation.
Further, there is significant agreement that, as increases in antibiotic resistance continue to
reduce our ability to treat infections, then infection prevention through hygiene, not only in
hospitals but also in the community, becomes of even greater importance (Anon 1999a, 2000;
Smith et al. 1999). Working parties across Europe and elsewhere engaged in implementing
strategies to reduce antibiotic prescribing in humans also acknowledge the need for improved
hygiene as a vital component of these strategies (Anon 1999a, 2000). The benefits of this
approach have been demonstrated in clinical settings where good hygiene has contributed to
reduced antibiotic resistance through reduced prescribing (Schmitz et al. 1998). Increasingly
it is also recognised that good home hygiene also has a role on preventing the spread of
antibiotic resistant strains which is increasingly seen as a community as well as a hospital
problem (Aiello and Larsen 2003, Calfee et al 2003).
Looking from this perspective, it is argued that if reducing the number of infections and the
spread of resistant strains through effective hygiene is important, then it is also important to
ensure that biocide use, as an integral part of good hygiene practice, is not discouraged in
situations where there is real benefit in terms of preventing infection transmission. Overall
there is strong evidence showing that good standards of hygiene can have a significant impact
in reducing the number of infections arising in the home. It is also concluded that within a risk
approach to home hygiene in situations where failure to achieve hygiene carries a risk of
serious consequences (e.g. food hygiene), or in the protection of vulnerable groups, we should
not be afraid to intervene with a disinfection process, either a heat process or an effective
chemical disinfectant which will inactivate pathogens including bacteria and preferably also
viruses. In making recommendations on the use of disinfectants in the home and other
environments however it is important to distinguish between “general “ and “targeted” use.
On the basis that concerns about antibiotic resistance remain unresolved the consensus view
of IFH remains as before, which is that there is need to ensure that biocides are used
responsibly i.e. in accordance with the recently published IFH “Recommendations for the
selection of suitable hygiene procedures for use in the domestic environment” (Beumer et al.
2000, http://www.ifh-homehygiene.org/public/hypro00.htm). IFH also recommends that, in
order to avoid the possibility of any impact on antimicrobial resistance in the future, reactive
biocides (e.g. peroxide and hypochlorite bleach) and those which evaporate (alcohols) which
disappear rapidly, leaving bacteria with no residue to which to develop tolerance should be
preferred.
REFERENCES
Akimitsu, N., Hamamoto, H., Inoue, R., Shoji, M., Akamine, A., Takemori, K., Hamasaki, N.
and Sekimisu, K. (1999) Increase in resistance of methicillin-resistant Staphylococcus
aureus to -Lactams caused by mutations conferring resistance to benzalkonium chloride,
a disinfectant widely used in hospitals. Antimicrobial Agents and Chemotherapy, 43, 30423043.
9
BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
Aiello, A.E. and Larson, E. (2003) Antibacterial cleaning and hygiene products as an
emerging risk factor for antibiotic resistance in the community. The Lancet infectious
diseases, 3. 501-506.
Anon (1999a) Official Journal of the European Communities C195, 1-3
Anon (1999b) Four pediatric deaths from community-acquired methicillin-resistant
Staphylococcus aureus - Minnesota and North Dakota 1997-1999. Morbidity and Mortality
Weekly Report 48, 707-710.
Anon (2000) UK Antimicrobial Strategy Action Plan. Department of Health, London, UK.
Armstrong, J. L., Calomiris, J. J. and Seidler, R.J. (1982) Selection of antibiotic resistant plate
count bacteria during water treatment. Applied and Environmental Microbiology, 44, 308316.
Bloomfield, S.F., Stewart, G.S.A.B., Dodd, C.E.R., Booth, I.R. and Power, E.G.M. (1998)
The viable but non culturable phenomenon explained? Microbiology 144, 1-2.
Calfee, D.P. Durbin, L.J. Germanson, T.P., Toney, D.M., Smith, E.B. and Farr, B.M. (2003)
Spread of methicillin resistant Staphylococcus aureus (MRSA) among household contacts
of individuals with nosocomially-acquired MRSA. Infection Control and Epidemiology ,
24, 422-426.
Cole, E.C., Addison, R.A., Rubino, J.R., Leese, K.E., Dulaney, P.D., Newell, M.S., Wilkins,
J., Gaber, D,J,. Weininger, T. and Criger, D.A. (2003) Investigation of antibiotic and
antibacterial agent cross resistance in target bacteria from homes of antibacterial product
users and non users. Journal of Applied Microbiology 95, 664-676
Dodd, C.E.R., Bloomfield, S.F., Booth, I.R. and Stewart, G.S.A.B. (1998) Suicide through
stress: a cell’s response to sublethal injury. The Biochemist April, 12-14.
Gilbert, P. Maira-Litran, T., McBain, A.J., Rickard, A.H. and Whyte, F. (2002) The
physiology and collective recalcitrance of microbial biofilm communities. Advances in
Microbial Physiology, 46, 203-256.
Gilbert, P. and McBain, A. (2003) Potential impact of increased use of biocides in consumer
products on prevalence of antibiotic resistance. Clinical Microbiological Reviews. 16,
189-208.
Levy, S.B. (1998) The challenge of antibiotic reistance. Scientific American March, 322-39.
Levy, S.B. (2000) Antibiotic and antiseptic resistance: impact on public health. Pediatric
Infectious Disease Journal 19, S120-S122.
Levy, S.B. (2001) Antibacterial household products: cause for concern. Emerging Infectious
Diseases, 7, 512-515.
Levy, S.B. (2002) Antibacterial household products: cause for concern. Emerging Infectious
Diseases 7, (no 3 supplement), 512-515.
Marshall, B.M., Roblet, E., Dumont, T., Billhimer, W., Wiandt, K., Keswick, B. , . Levy;
S.B. (2003), The Frequency of Bacteria and Antibiotic Resistance in Homes that Use and
do not Use Surface Antibacterial Agents. Abstracts of the Annual Meeting of the American
Society for Microbiology. A-147
McBain, A.J, Bartelo, R.G., Catrenich, C. E., Charbonneau, D., Ledder, R.G., Price, B.B and
Gilbert, P. (2003a) Exposure of sink drain microcosms to triclosan population dynamics
and antimicrobial susceptibility. Applied and Environmental Microbiology 69, (in press)
McBain, A.J, Bartelo, R.G., Catrenich, C. E., Charbonneau, D., Ledder, R.G., Price, B.B and
Gilbert, P. (2003b) Effects of a chlorohexidine gluconate containing mouthwash on the
vitality and antimicrobial susceptibility of an in vitro oral bacterial ecosystem. Applied and
Environmental Microbiology 69, 4770-4776.
10
BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
McBain, A.J, Bartelo, R.G., Catrenich, C. E., Charbonneau, D., Ledder, R.G., Price, B.B and
Gilbert, P. (2003c) Effects of a triclosan-containing rinse on the dynamics and
antimicrobial susceptibility of in vitro plaques ecosystems. Antimicrobial Agents and
Chemotherapy, 47, 3531-3538.
McDonnell, G. and Russell, A.D. (1999) Antiseptics and disinfectants: activity, action and
resistance. Clinical Microbiology Reviews 12, 147-179.
McMurry, L.M., Oethinger, M. and Levy, S.B. (1998) Overexpression of marA, soxS or
acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli.
FEMS Microbiology Letters 166, 305-309.
McMurry, L.M., McDermott, P.F. and Levy, S.B. (1999) Genetic evidence that InhA of
Mycobacterium smegmatis is a target for triclosan. Antimicrobial Agents and
Chemotherapy 43, 711-713.
Miller, P.F. and Sulavick, M.C. (1996) Overlaps and parallels in the regulation of intrinsic
multiple-antibiotic resistance in Escherichia coli. Molecular Microbiology 21, 441-448.
Moken, M.C., McMurry, L.M. and Levy, S.B. (1997) Selection of multiple-antibioticresistant (Mar) mutants of Escherichia coli by using the disinfectant pine oil: roles of the
mar and acrAB loci. Antimicrobial Agents and Chemotherapy 41, 2770-2772.
Murray, G.E., Tobin, R.S., Junkins, B. and Kushner, D.J. (1984) Effect of chlorination on
antibiotic resistance profiles of sewage-related bacteria. Applied and Environmental
Microbiology 48, 73-77.
Parikh, S.L., Xiao, G., Tonge, P.J., (2000) Inhibition of InhA, the enoylreductase from
Mycobacterium tuberculosis by triclosan and isoniazid. Biochemistry 30, 7645-7650..
Potenski, C.J., Ghandi, M. and Mathews, K.R. (2003) Exposure of Salmonella Enteritidis to
chlorine or food preservatives increases susceptibility to antibiotics. FEMS Microbiology
Letters, 220, 181-186.
Rickard, A.H., Lindsay, S. and Gilbert, P. Indiction of mar operon by miscellaneous groceries
(in press).
Rook, G.A.W. and Stanford, J.L. (1998) Give us this day our daily germs. Immunology Today
19, 113-116
Rouche, D.A., Cram, D.S., DiBernadino, D., Littlejohn, T.G. and Skurray, R.A. (1990)
Efflux-mediated antiseptic gene qacA from Staphylococcus aureus: common ancestry with
tetracycline- and sugar-transport proteins. Molecular Microbiology 4, 2051-2062.
Russell, A.D., Suller, M.T.E. and Maillard, J.Y. (1999a) Do antiseptics and disinfectants
select for antibiotic resistance? Journal of Medical Microbiology 48, 613-615.
Russell, A.D. and Maillard, J-Y. (2000) Response. American Journal of Infection Control 28,
204-206.
Rutala, W.A., Weber, D.J., Barbee, S.I., Gergen, M.F. and Sobsey, M.D. (2000) Evaluation
of antibiotic resistant bacteria in home kitchens and Bathrooms. Infection Control and
Epidemiology 21, 132.
Schmitz, F-J., Verhoef, H., Idel, H., Hadding, U., Heinz, H.P. and Jones, M.E. (1998) Impact
of hygienic measures in the development of methicillin resistance among staphylococci
between 1991 and 1996 in a university hospital. Journal of Hospital Infection 38, 237-240.
Sidhu, M.S. Heir, E., Sorum, H. andHolk, A. (2001) Genetic links between resistance to
quaternary ammonium compounds and B-lactam antibiotics in food-related Staphylococcus
species. Microbial Drug Resistance, 7, 363-371
Slayden, R.A., Lee, R.E., and Barry, C.E. (2000) Isoniazid affects multiple components of the
type II fatty acid synthase system of Mycobacterium tuberculosis. Molecular
Microbiology, 38, 524-528.
11
BIOCIDES USAGE AND MICROBIAL RESISTANCE UPDATE
Smith, T.L., Pearson, M.L. and Wilcox, K.R. (1999) Emergence of vancomycin resistance in
Staphylococcus aureus. New England Journal of Medicine 340, 493-501.
Whyte, F.W., Allison, D.G., Jones, M.V and Gilbert, P. (2001) In vitro detection of multidrug
antibiotic resistant (Mar) phenotype induction by miscellaneous groceries. Abstracts of the
104th Meeting of the American Society for Microbiology, A99.
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