EU experts assess the role of biocides in antibiotic resistance

Ian Schofield - Analyst
14 November 2008

Could washing the dishes or applying make-up be contributing to the rise in antibiotic resistance? This is the worrying prospect raised by an advisory committee to the European Commission which suggests that biocides used in many household detergents and cosmetics, as well as in various healthcare and industrial applications, may play a role in the development of bacterial resistance to current therapies.

As the use of antibiotics has grown, so has concern about the increasing resistance of various bacteria and the resultant failure of some treatments for infectious diseases in both humans and animals.

Scientists and regulators are worried that soon many of the antibiotics that are now on the market will no longer be effective. Earlier this year, the UK Health Protection Agency (HPA) warned that resistance was continuing to accumulate and that the NHS should be more careful in its use of antibiotics, while the American College of Physicians has spoken of a "worldwide public health problem that continues to grow".

Some are also worried that not enough new pharmaceutical treatments are being developed to replace those that are losing their effectiveness. In an interview with Scrip earlier this year, Thomas Lönngren, executive director of the European Medicines Agency, lamented the fact that while the agency was receiving many applications for innovative drugs for diseases such as cancer, it was seeing none for new antibiotics.

The scale of the concern in the EU is such that the Community has launched an annual "European Antibiotic Awareness Day", the first of which will be held on November 18th. The aim is to alert the public and healthcare professionals to the need to use antibiotics in a rational way.

what's the story?

The main culprit for the rise in resistance is the excessive and often inappropriate use of antibiotics in humans, often for viral infections such as coughs, colds and sore throats.

Another area of concern is the use of antibiotics as growth promoters in food animals, which has been cited as a factor in generating cross-resistance to antibiotics in humans.

Now, though, attention is turning to the possible role of other substances, such as those used in various kinds of biocides. According to the commission's scientific committee on emerging and newly identified health risks (SCENIHR), there is evidence that biocides can trigger bacterial resistance, and more research needs to be done to see how extensive a problem this might be.

wide range of uses

Biocides are used to control the growth of bacteria in a huge range of applications, from cosmetics and personal care products to laundry detergents, cleaning fluids, food and feed preservatives, and building materials.

In the healthcare setting, they are used as disinfectants for medical devices, and in antimicrobial wipes and the alcohol-based hand rubs that are now used for routine disinfection in hospitals to help combat the spread of infections.

Examples of common biocides are quaternary ammonium compounds, aldehydes and alcohols, which are widely used by the food and pharmaceutical/cosmetics industries as preservatives. Triclosan is used in disinfectants, cosmetics, toothpaste, cleaning products, paint, textiles and plastic products, while chlorhexidine is found in many antiseptic products. 

In 2006, the European market for biocides amounted to around €10-11 billion, having shown annual growth of some 4-5% over the previous 15 years, according to SCENIHR.

effects under review

The problem is that no one really knows what volumes of biocides are being used, in which areas, and what their individual and cumulative effects might be.

Since 1998, many biocides have been governed by Directive 98/8/EC, which provides for biocidal products and their active substances to be assessed at Community level, with member states then authorising them under a mutual recognition system.

The directive covers 23 different product types. However, it does not apply to biocides regulated by other EU legislation in areas such as medicines, cosmetics, food contact materials and plant protection products. Nor does it cover goods treated with biocides imported from third countries. This means, says SCENIHR, that the cumulative risks and impacts resulting from biocide use outside the scope of the directive are not addressed in the evaluation process.

The potential for biocides to cause resistance to antibiotics has been suspected for some time, even if evidence has been thin on the ground.

In its 2002 opinion on triclosan, the EU's scientific steering committee said that the potential for biocides to induce cross-resistance to antimicrobials should be kept under review, and that if new evidence were to indicate a significant risk, then action would need to be taken.

Evidence has subsequently emerged suggesting that biocides may indeed contribute to the increased occurrence of antibiotic-resistant bacteria. In light of this, the commission decided to ask SCENIHR to look into the matter and produce an opinion.

It asked what scientific evidence there was that the use of certain substances in biocidal products could contribute to antibiotic resistance, which substances or uses might create the highest risks, and how the development of such resistance might be assessed.

The committee was specifically asked to consider whether the risk of exposure to biocides might favour the emergence of cross-resistance mechanisms that could reduce the efficacy of antibiotics during therapy.

It looked into the available evidence, focusing on all the main applications in areas like healthcare, consumer and household products, food production and animal husbandry. It also examined data on the common resistance mechanisms shared by biocides and antibiotics.

the role of biocides

In its preliminary opinion, which has just been put out for consultation, SCENIHR says that one way in which biocides might contribute to the occurrence of antibiotic-resistant bacteria is when the bacterial flora on human skin and in the home environment are repeatedly exposed to antimicrobial agents in household and personal hygiene products.

This leads to certain microbes being less susceptible to specific biocides, and could in turn lead to those microbes becoming resistant to antibiotics, although the committee says that the studies currently available are inconclusive as to this mechanism.

It says the two most studied kinds of biocides, triclosan and quaternary ammonium compounds, are probably instrumental in causing resistance, although the lack of data on other biocidal compounds means it cannot reach a definitive conclusion on their role.

It notes that biocides are "invaluable compounds that provide society with numerous benefits", and that in order to preserve their role in infection control and hygiene, it is important to ensure their "appropriate and prudent use".

recommendations

To do this, SCENIHR says, standard protocols for assessing antimicrobial resistance induced or selected by biocides will be needed to provide useful data for the development and use of biocidal products and for regulatory bodies.

One aim should be to develop tools to determine the "minimal selective concentration" - ie the lowest concentration at which a biocide is able to select or induce the emergence of a resistance mechanism.

The committee also calls for more studies on the mechanisms of cross-resistance and on the emergence of biocide-induced antibiotic resistance in the various fields of application, including healthcare. Surveillance programmes should be set up to monitor developments in this field, particularly in the healthcare, veterinary and food industry settings, it recommends.

The SCENIHR opinion is out for consultation, and comments are invited until November 30th.

If the substances contained in biocides were indeed found to be a trigger for antibacterial resistance, it could have huge implications for industry, consumers, scientists and the government. It could mean a complete reassessment of the way biocides are used, at what concentrations, and in which settings.

But given the huge numbers of biocides and the wide range of uses to which they are put - from sterilising medical equipment to preserving food and making plastics - is it feasible even to monitor their effects, never mind do anything about them?

One thing is for sure. If biocides were found to play a role in increasing overall bacterial resistance, it would add even more urgency to calls for new antibiotics to be developed before current therapies are rendered ineffective.

Resistance is certainly a high priority for the health authorities. This year the UK Department of Health began an awareness campaign to encourage the more prudent use of antibiotics, saying that resistance is "now a major cause of concern".

And to coincide with the first "European Antibiotic Awareness Day" on November 18th, the DH's advisory committee on antibiotic resistance is organising a national conference at the Science Museum in London, targeted at health science journalists and health professionals.

Among the topics will be the development of new drugs and the use of antibiotics in farming and agriculture. The potential contribution of biocides to antibiotic resistance might be a useful addition to the agenda.

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