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The Clinical Treatment of Pet Dogs and Antibiotic Resistance in Commensal and Potentially Pathogenic Bacteria


Antibiotic resistance in bacteria capable of causing infections compromises the treatment of infected people and animals, and is of international concern. Much past attention has centred on food animals and this has led to radical changes in the administration of antibiotics to these animals, particularly in their feed and water, when given prophylatically and/or as growth promoters. There is, however, another animal-related source of antibiotic-resistant bacteria, which is of potentially great importance and which has received much less attention. This is antibiotic resistance resulting from the treatment of infections in pet animals. Around 53% of UK households own at least one pet animal and it is estimated that there are ~9 million cats, ~7 million dogs and ~1.5 million pet rabbits in the UK. Many of these will receive antibiotic treatment during their life for a range of conditions and, for example, in the Univeristy of Bristol referral practice for small animal dermatology cases, 33% of either cats or dogs were prescribed antibiotics in 2005. The antibiotics used are often the same as those in human medicine. However, the potential impact of this on human and animal health is not known to any great extent. Given the often close contact that owners have with their pets it is important to establish the risks posed by the carriage of resistant bacteria by such animals and the impact that commonly applied treatments have on carriage rates. This information will make it possible to identify which antibiotics, treatment regimes and/or infections pose the greatest risk of generating antibiotic-resistant bacteria. Control options can then be better identified. <P>

The antibiotic treatment of food animals has been shown to lead to resistance in both pathogenic and commensal bacteria and these organisms can enter the food chain. Thus with food animals the main risk to human health is the consumption or handling of contaminated food. With pets the greatest risk is transmission by contact between the pet and its owner(s). Both can also act as disseminators of resistant bacteria to other people and animals and the environment. The fact that pets have been shown to carry multi-antibiotic-resistant salmonella and resistant Staphylococcus aureus (MRSA) means that such transmission is of particular importance. <P>

The proposed project will be a multi-centre collaboration between the Universities of Bristol and Liverpool and the Veterinary Laboratories (VLA) and Health Protection (HPA) Agencies. It is planned to examine the impact of treatment on the prevalence of antibiotic-resistant bacteria, both pathogenic and commensal, in cats, dogs and rabbits being treated at the small animal hospitals of both Universities and at selected veterinary practices. The animals will be sampled at sites with the greatest risk of zoonotic transfer. Thus samples will comprise swabs from the area around the nose and mouth and faeces and will be taken before treatment begins and when it ends. Animals being treated for any infection will be included in the study and data on animal type, clinical diagnosis and treatment given will be recorded and used in data analysis. The samples will be examined for potentially pathogenic bacteria such as Campylobacter and Salmonella spp, Clostridium difficle and MRSA and also for certain commensal bacteria like enterococci. In addition, and because gene transfer is possible between many bacteria species, the swab and faecal samples will be examined using molecular techniques for the presence of bacterial genes conferring resistance to the commonly used antibiotics. Samples and isolated bacteria will also be stored at -80C to make it possible to carry out subsequent work, should that be required. The involvement of HPA will make it possible to compare antibiotic resistance patterns in the pet-associated bacteria with those from patients in hospital and the community. <P>

This project will provide information, which will lead to science based risk assessments on the use of antibiotics in small animal medicine. It will also allow the design of treatment regimens where the risks of generating antibiotic-resistant bacteria are minimised.
The proposed work will have three objectives:
<P> The first, and principal objective, is to examine the impact of commonly used antibiotics for the clinical treatment of cats and dogs on the carriage of antibiotic-resistant pathogenic and commensal bacteria.
<P>The second objective is to ascertain whether antibiotic therapy results in changes in abundance of selected common genes associated with antibiotic resistance in cohorts of bacterial isolates.
<P> The third is to examine changes in the abundance of resistance genes in the total microbial population present in the samples taken.

<OL> <LI> The impact of commonly used antibiotics for the clinical treatment of cats and dogs on the carriage of antibiotic-resistant pathogenic and commensal bacteria.

<BR> l.l To work with staff at Bristol and Liverpool Universities small animal hospitals, and commercial veterinary practices to establish identification and sampling regimes for the target animal populations
This will ensure that the appropriate number of samples, supported by the relevant clinical information, is collected for the project. The involvement of both Bristol and Liverpool Universities, and diverse commercial practices, will ensure a good geographical spread and socio-economic diversity.

<BR> 1.2. To receive faecal samples and swabs from the mouth and nose region from cats and dogs, pre- and post- treatment with antibiotics
The sampling of both the intestinal tract and, to a lesser extent, the oral/nasal areas will ensure that the potential impact of the two major routes of bacterial transmission is examined. The sites were chosen as they represent those with the greatest risk of zoonotic transfer.

<BR> 1.3. To examine the above specimens for the presence and numbers of antibiotic-resistant pathogenic and commensal bacteria
The inclusion of both pathogenic and commensal bacteria will allow an assessment of both direct and indirect risks to human and animal health.

<BR> 1.4. To use multivariate models to investigate risk factors for the isolation of antimicrobial-resistant bacteria from companion animals
Epidemiologists from CERA-VLA will advise on data collection in order to ensure that an appropriate project structure is put in place and that data are analysed with the highest possible rigour in order to maximise the value of the new knowledge that is gained from the project.

<LI> Determining presence of genes associated with antibiotic resistance before and after therapy

<BR> 2.1. To determine, using PCR, whether antibiotic therapy relates to changes in the abundance of genes associated with antibiotic resistance for selected populations of the bacteria and the total microbial load in the samples taken
Up-to-date, post-genomic, analysis tools will be used to determine possible changes in the abundance of genes responsible for causing antibiotic resistance.

<LI> Supporting objectives

<BR> 3.1. Formation of a project steering group
To monitor progress, provide expert advice and to keep stakeholders informed.

<BR> 3.2. Production of reports and advice for UK veterinarians and dissemination of information by the production of papers for peer-reviewed and trade publications
To ensure that Defra and the veterinary profession gains maximum benefit from the research.

<BR> 3.3. To submit interim and final reports to Defra

University of Bristol
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