Effects of Biocides on antibiotic resistance

9. Conclusions & recommendations

The SCENIHR opinion states:

EXECUTIVE SUMMARY

Antibiotic resistance has increased worldwide in bacterial pathogens leading to treatment failures in human and animal infectious diseases. Resistance against antibiotics by pathogenic bacteria is a major concern in the anti-infective therapy of both humans and animals. Bacteria are able to adapt rapidly to new environmental conditions such as the presence of antimicrobial molecules and, as a consequence, resistance may increase with increasing exposure to antimicrobials. Serious concerns about bacterial antibiotic resistance from nosocomial, community-acquired and food-borne pathogens have been growing for a number of years, and have been raised at both national and international levels.

Emerging bacterial resistance against different types of biocides (including disinfectants, antiseptics, preservatives and sterilants) has been studied and characterised only recently. Only limited scientific evidence is available to correctly weigh the risks of antibiotic resistance induced by resistance to biocides and some controversies remain. Furthermore, research indicates that biocides and antibiotics may have some similar and common interactions and target sites with bacteria, which might express shared resistance mechanisms to both antimicrobials.

Therefore the Commission requested the SCENIHR to answer the following questions:

1. Does current scientific evidence indicate that the use of certain active substances in biocidal products in various settings as mentioned above can contribute to the occurrence of antibiotic resistant bacteria, both in humans and in the environment? If so, how does this effect compare to resistance due to application of medicinal products or veterinary medicinal products and other relevant applications?
2. If yes, which types of active substances, modes of action or areas of application create the highest risks for increasing antibiotic resistance?
3. If yes, what are the extent of the resulting antibiotic resistance and the relative contribution of the different applications to the risk of increasing antibiotic resistance?
4. How can the development of antibiotic resistance due to the use of active substances in biocidal products be examined? Could the Committee advise on the methodologies?
5. Please identify relevant gaps in scientific knowledge and suggest major research needs.

Biocides are invaluable compounds that provide society with numerous benefits. They play an important role in the control of bacteria in a variety of applications and are thus a precious resource that must be managed so as to be protected from loss of activity over time. Therefore, in order to preserve the role of biocides in infection control and hygiene, it is paramount to prevent the emergence of bacterial resistance and cross-resistance through their appropriate and prudent use.

Current scientific evidence (including bacteriological, biochemical and genetic data) does indicate that the use of certain active substances in biocidal products in various settings may contribute to the increased occurrence of antibiotic resistant bacteria. Some mechanisms of resistance are common to both biocides and antibiotics (e.g. efflux pumps, permeability changes and biofilms). The selective pressure exerted by biocides may favour the expression and dissemination of these mechanisms of resistance. The most studied biocides; triclosan and quaternary ammonium compounds, are likely to contribute to maintaining selective pressure allowing the presence of mobile genetic elements harbouring specific genes involved in the resistance to biocides and antibiotics. However, the lack of data on the other biocidal compounds prevents reaching a definitive answer as to their role in selecting for or maintaining bacterial antibiotic resistance. The existence of horizontal gene transfer, particularly associated with mobile genetic elements, is the most likely mechanism for selecting and increasing antibiotic resistance. The dissemination of these mobile genetic elements, their genetic capacity to contain several resistance genes, and the presence of overlapping genetic cascades of regulation responding to selective pressures from chemicals on bacteria represent the highest risk factors. The formation of biofilms could also be considered a potential risk factor for the development of cross-resistance between antibiotics and biocides.

In the face of the large increase of biocide use in various fields (human, animals, foods etc.) and the continuous increase in bacterial antibiotic resistance, there is a serious lack of data and methodologies to clearly identify the risks arising from the indiscriminate use of biocides:

1. Quantitative data on biocide exposure including concentrations, environmental conditions affecting activity (e.g. temperature, organic load, exposure time etc.), dissemination of resistance genes, change in bacterial population following exposure, and potential synergies with other molecules are required to formulate an appropriate risk assessment.
2. There are no accepted standard protocols for the evaluation of antimicrobial resistance induced or selected by a biocide. Such standards must be developed to provide informative data for biocidal product development and usage, and for regulatory bodies. In addition, surveillance programmes must be introduced to monitor the level of bacterial resistance and cross-resistance in all areas of biocide usage.
3. Environmental studies focussing on the identification and characterisation of resistance and cross-resistance to antibiotics following use and misuse of biocides.

All suggestions and questions raised at the occasion of the public consultation on this opinion were taken into account and adequate responses were formulated in the final version

Source & ©: SCENHIR,  Assessment of the Antibiotic Resistance Effects of Biocides (2009),
Executive Summary, p. 8-10
 http:///ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_021.pdf