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Potential risk to human and animal health from the emergence and spread of beta-lactamase resistance in animals in GB - OD2023

Problems of bacterial resistance to extended spectrum cephalosporins have been increasingly reported since the introduction of these antibiotics into medical clinical practice. The emergence of resistance to this group of drugs is of particular concern, as extended spectrum cephalosporins are one of the most important of the recommended treatments for infections in children, and may also be used in other patients with invasive disease. Initially resistance to broad-spectrum cephalosporins and monobactams was limited to nosocomial pathogens (Pseudomonas, Citrobacter and Enterobacter) that carried an inducible chromosomally located beta-lactamase gene of the AmpC type. In the late 1980s plasmid mediated ESBLs emerged. Over 150 ESBL enzymes have now been described isolated from a wide variety of enterobacteriaceae. Worldwide there have been only a few reports of ESBL-containing animal strains. We recently reported the detection of a CTX-M enzyme in Escherichia coli recovered from diarrhoeic calves on a UK dairy farm (Vet Rec [2005], 156: 186-187). This type of ESBL was reported in human E. coli isolates in the UK in 2000-2001 but this is thought to be the first report of an E. coli containing an ESBL from livestock in the UK. The occurrence of this resistance in animals could lead to amplification of the problem due to the relatively common use of beta-lactam antibiotics in animal husbandry and this could potentially be of serious concern for both animal and public health. Third generation cephalosporins such as ceftiofur are in regular use in food animal and companion animal clinical therapy and preventatively as dry cow therapy in dairy cattle. Currently VLA is seeking to develop the appropriate methodology to carry out surveillance for the emergence of extended spectrum cephalosporin resistant organisms in food animal production.

This proposal is intended to act as a means of developing and evaluating techniques for use in surveillance programmes and special investigations of ESBL-mediated resistance. Our aims are:

1. To investigate in more detail the epidemiology of CTX-M isolates associated with the affected Welsh dairy farm (CTX-M index farm); including, with permission from the individuals involved, a study of whether transfer has occurred to the farmer, farm workers and their families.

2. To investigate prevalence of ESBL-producing E. coli through retrospective screening of existing samples (animal and human).

3. To conduct pilot studies in order to develop suitable surveillance approaches for the identification and follow up of new and emerging ESBLs in food animal production.

4. To use social network analysis and develop a model for investigating spread of a new and emerging condition.

5. To generate data on the transferability and persistence of the ESBL resistance identified.

6. To provide Defra with a literature review of ESBLs, with particular emphasis on veterinary and public health aspects.

7. To investigate the prevalence of ESBL producing E. coli through screening of chicken caeca from the EU campylobacter broiler survey (OZ 0613).

Detailed longitudinal studies will be conducted on the index farm. Questionnaires will be used to collect data on management, disease status and antimicrobial usage. Faeces will be collected longitudinally from a cohort of newborn calves to assess the acquisition of E. coli containing the resistance plasmid. Faeces and environmental samples will be collected from other age groups on the farm to assess distribution and persistence of resistant organisms. Laboratory studies will investigate which bacteria carry the resistance plasmid(s), the proportion of the bacterial population affected and characteristics of the plasmid(s). Comparisons will be made with human data derived from microbiological investigation of samples taken from the farm staff and/or toilets on the farm. Clinical samples from the locality and further afield and archived isolates will also be screened for ESBLs
To establish the pattern of spread of CTX-M from the index farm to the rest of the population, social network analysis will be used to investigate the movement of animals between the index farm and the surrounding or more distant population.
Results will be presented in scientific reports, publications and presentations. Recommendations will be produced for investigation of and response to new and emerging antimicrobial resistances.
1. Developing a strategy to monitor and investigate the epidemiology of a new and emerging disease using ESBL as an example (led by Epidemiology, CERA)

2. Microbiological studies in livestock (led by FES)

3. Studies of human populations in contact with the index farm (led by HPA/NPHS Wales)

4. Complete a literature review of ESBLs, with particular emphasis on veterinary and public health aspects.

5. Surveillance for ESBLs in Broilers in the UK: Abattoir Survey 2008.
Project Documents
• FRP - Final Report : OD2023 final report for upload   (800k)
Time-Scale and Cost
From: 2007

To: 2010

Cost: £660,030
Contractor / Funded Organisations
Veterinary Laboratories Agency
Antimicrobial Resistance              
Food Safety              
Public Health              
Fields of Study
Animal Health