Potential Risk to Human and Animal Health from the Emergence and Spread of Beta-Lactamase Resistance in Animals in GB

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. <P>
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 expended spectrum cephalosporin resistant organisms in food animal production. <P>
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, and help evaluate the risk to human and animal health of the emergence of such resistance in animals. Our aims are:

<OL> <LI> 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 thansfer has occurred to the farmer, farm workers and their families.

<LI> 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.

<LI> To generate data on the transferability and persistence of the ESBL resistance identified, and to use data from the studies to parameterise a risk model.

<LI> To identify risk pathways and assess the risk to the food chain and human health from the CTX-M index farm using a framework that could be used for informing future contingency plans relating to the emergence of new conditions in cattle.
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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 and environmental samples will be collected from all age groups 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. <P>

Risk assessment methodology will be developed from which an estimate of the likelihood of E. coli carrying the CTM-X enzyme entering the food chain (via milk and beef) will be obtained. Although the work will focus on the CTM-X index farm, similar methods could be applied to other situations where there is a risk to animal health/veterinary public health due to a new condition emerging on a cattle farm. To achieve this both qualitative and quantitative risk assessment methods will be utilised and will not only consider the consequences of this isolation on the farm (i.e. spreading of infection within the entire farm management system), but also the human health consequences. We aim to identify and qualitatively assess the key risk pathways that are associated with the risk (a) to human health, (b) of spread within the farm and (c) of the infection being transferred to another farm (animal movements or environmental). From this initial work, a quantitative risk model describing the entire management system of the index farm and the dynamics of the infection on the farm both in the cattle and the environment will be developed from which an estimate the likelihood of entering the food chain (via milk and beef) will be obtained.
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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.

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Objective: <OL> <LI>
Developing a strategy to monitor and investigate the epidemiology of a new and emerging disease using ESBL as an example (led by Epidemiology, CERA)

<LI> Microbiological methods and detailed bacteriological studies at the index farm (led by FES)

<LI> Studies of human populations in close contact with the index farm (led by HPA)

<LI> Development of Risk models (led by Risk Analysis, CERA)

<LI> Development of a generic contingency plan and a generic approach to risk assessment for non-notifiable new and emerging conditions