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Measure  –  Antibiotic resistance

Antibiotic resistance in animals

Here you find guidance, methods and tools to measure occurrence of antibiotic resistance in animal settings.

Data on antibiotic resistance in animal settings can be generated on a small or large scale. Conducting point prevalence surveys is a good way to get started and can be a useful tool to quickly assess the current situation. Over time efforts can be scaled up and eventually act as inputs to national surveillance. Besides scarcity of resources, a main challenge for monitoring resistance in livestock is the harmonization among countries of analytic methods as well as sampling frames.

Which bacteria to monitor?

In the animal sector, three categories of bacteria usually are included in surveillance programs:

  1. Zoonotic bacteria. These bacteria can develop resistance in the animal reservoir and may also transfer to and cause infections in man.
  2. Indicator bacteria. These bacteria are isolated from healthy individuals and give a more accurate value of the occurrence of resistance in the entire animal population
  3. Animal pathogens. Pathogenic isolates from clinical sampling are usually not representative for the true occurrence of resistance, but are important for detecting emerging resistance.

In the EU and USA, surveillance covers zoonotic bacteria (Salmonella spp, Campylobacter jejuni and Campylobacter coli) and indicator bacteria (commensal E. coli, Enterococcus faecalis and Enterococcus faecium) isolated from healthy animals and food.

Pathogenic bacteria from clinical cases are at present included in some national surveillance programs. Many of these samples are likely from animals treated with antibiotics. This has to be taken into account when analyzing such data. However, there is a need for harmonized monitoring of data for certain types of resistance in certain animal pathogens to be able to detect emerging resistance that could lead to severe therapy failure. An example is pleuromutilin resistance in Brachyspira hyodysenteriae , the bacterium that causes swine dysentery (see grey box).

The burden of antibiotic resistance – swine dysentery

Swine dysentery is an enteric disease of pigs caused by the bacterium Brachyspira hyodysenteriae. The disease is found worldwide with an estimated prevalence between 0 to near 40%.

At present only few treatment options remain to control clinical outbreaks of swine dysentery. Resistance to antibiotics is common, and for example in the EU, pleuromutilins are the only potentially effective choice. In a recent study from Italy, more than 50% of the isolates were resistant.

Swine dysentery causes impaired growth, and severe forms of the disease have mortality rates reaching 50-90%. Lack of effective treatment options would have considerable impact on animal health and production economy.

Eradication programs have successfully been applied in some EU countries, and the European Medicines Agency (EMA) has stressed that such programs are crucial to reduce the need for pleuromutilins. Also, harmonized monitoring for pleuromutilin resistance has been proposed.

A successful protocol for elimination of swine dysentery from single-site, farrow-to-finish herd has been described. Eradication from farms has resulted both in higher productivity and decreased use of antibiotics.

Sampling sites and types

The main part of bacterial samples in animal surveillance systems is derived from healthy animals. Fecal samples at farm level or samples from caecal content taken at the slaughterhouse dominate. Also, as samples are taken from animal-derived food, sampling sites include retail foods. When starting up a surveillance program in the animal sector, sampling retail food for resistance can be a start, progressively expanding the sampling to food producing animals.

Slaughterhouses are usually the most cost-efficient sampling sites for animal samples, even though the caecal microbiota of the animal may change during transportation and in holding pens at the slaughterhouse. Examples of what to consider when taking bacterial samples throughout the food chain is presented in figure 1.

Sample sites should be connected to a laboratory facility, either on site or if samples can be stored and transported properly, to a central laboratory. The laboratory should at least have the capacity to isolate and identify target bacteria and perform antibacterial susceptibility testing using validated methods according to established standards.

Flow chart of considerations for sampling through the food chain. Adapted from WHO/AGISAR, 2013 as explained in the text
Figure 1. Considerations for sampling for antibiotic resistant bacteria through the food chain. Adapted from WHO/AGISAR 2013.

The selection of which food and which animal species to sample from should reflect production and antibiotic consumption patterns in the studied region. The database of the Food and Agriculture Organization of the United Nations (FAO) summarizes production data for different countries and is a useful source of information for this purpose.

Susceptibility testing of bacteria

The most frequently used tests to determine if bacteria are susceptible or resistant to antibiotics are disc diffusion tests and minimum inhibitory concentration (MIC) tests. The MIC is the lowest concentration of an antibiotic that inhibits the growth of a bacterium. All results should be reported, whether bacteria are susceptible or resistant. For example the European Committee on Antimicrobial Susceptibility testing (EUCAST) provides break point values used in the European countries and are free of charge. EUCAST also has a subcommittee dealing with animal pathogens and bacteria with zoonotic potential, VetCAST.

Please note that it is very important that all products used in susceptibility testing are of good quality. EUCAST issues warnings about known quality issues on their website.  

Data management

To be able to contribute to national and international surveillance, retrieved data should be entered into a data management software. WHONET fulfils the demands for surveillance and is available free of charge. It is already used in hospital, public health, veterinary and food laboratories in over 100 countries and is available in over 20 languages. WHONET includes a feature for exporting resistance statistics into the format required for producing local and national reports and for uploading to the WHO Global Antimicrobial Resistance Surveillance System (GLASS) web interface. At present (2019) GLASS only includes human surveillance, but it will be extended to the food chain in the coming years.

Resources below have been divided into the following tables:

  • Tools and guidelines
  • Data and reports

One Health resources are found on the Antibiotic resistance page.

Selected Resources

Tools and guidelines

Resource Description
Manual of Diagnostic Tests and Vaccines for Terrestrial Animals Manual from WOAH providing standards, guidelines and recommendations for diagnosis and identification of important diseases and causative organisms in terrestrial animals. Chapter 2.1.1: Laboratory methodologies for bacterial antimicrobial susceptibility testing (PDF) explains how antimicrobial susceptibility tests should be performed.
Antimicrobial susceptibility testing by EUCAST Guidelines with step by step instructions on how to do susceptibility tests, including clinical breakpoint tables, developed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). See also video instructions with subtitles available in several languages.
Isolation and Antimicrobial Susceptibility Testing from GFN laboratory training courses

Protocol collection used in the laboratory training courses by the Global Foodborne Infections Network (GFN). It includes guidelines and protocols for antimicrobial susceptibility testing​ and isolation of enteric pathogens from food and animal faeces.

Reports and protocols for serotyping and antimicrobial susceptibility testing provided by the External Quality Assurance System (EQAS) are available here

Veterinary Committee on Antimicrobial Susceptibility Testing (VetCAST)

Information portal of a EUCAST subcommittee that deals with antimicrobial susceptibility testing of bacterial pathogens of animal origin and animal bacteria with zoonotic potential.
WHONET Software Database software for the management and analysis of antibiotic resistance data. The system is free to download and use, developed by WHO.
WOAH Aquatic Animal Health Code Guidelines from WOAH to development and harmonisation of national antimicrobial resistance surveillance and monitoring programmes for aquatic animals. Chapter 6.3: Monitoring of the quantities and usage patterns of antimicrobial agents used in aquatic animals.
CODEX ALIMENTARIUS International Food Standards: Antimicrobial Resistance Standards/Guidelines for the responsible use of antimicrobials in food-producing animals.The “Code of practice to minimize and contain antimicrobial resistance” (CAC/RCP 61-2005) describes the responsibilities for regulatory authorities, veterinary pharmaceutical industry, wholesalers, retailers, veterinarians and farmers. “Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance” (CAC/GL 77-2011) gives guidance on assessing the risk to human health from foodborne antibiotic resistant bacteria, and determining appropriate management strategies to control those risks. Available in English, French and Spanish.

Data and reports

Resource Description
Resistance bank Database. Repository of antimicrobial resistance data from individual point prevalence surveys done in animal populations. Links to video tutorial. Provides downloads of country reports based on existing data (please note that the data are aggregated and extrapolated and may be scarce). Focuses on Central and Latin America, Africa and Asia.
Review of Evidence on Antimicrobial Resistance and Animal Agriculture in Developing Countries Review providing available evidence on resistance in agri- and aquaculture in LMICs, highlighting the scarcity of most data and providing an overview of the gaps in knowledge.
The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2017 Report giving an overview of antimicrobial resistance data in zoonotic Salmonella and Campylobacter species from humans, animals and food, and resistance in indicator Escherichia coli as well as methicillin-resistant Staphylococcus aureus in animals and food from 28 European Union Member States.

More from "Antibiotic resistance"

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World Organisation for Animal Health - WOAH. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. https://www.oie.int/en/what-we-do/standards/codes-and-manuals/terrestrial-manual-online-access/.
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Aquatic Animal Health Code. (World Organisation for Animal Health - WOAH, Paris).
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Protocols used in the GFN laboratory training courses. https://antimicrobialresistance.dk/protocols.aspx.
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World Health Organization - WHO. Global Antimicrobial Resistance Surveillance System - Technical meeting on the early implementation phase. WHO https://apps.who.int/iris/handle/10665/204117 (2015).
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World Health Organization - WHO. WHONET - The Microbiology Laboratory Database Software.
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ETH Zürich & Center for Disease Dynamics, Economics & Policy - CDDEP. Resistance bank. https://www.resistancebank.org/.
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Swedish National Veterinary Institute - SVA & Public Health Agency of Sweden. Swedres-Svarm reports. https://www.sva.se/en/our-topics/antibiotics/svarm-resistance-monitoring/swedres-svarm-reports/.
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Food and Agriculture Organization of the United Nations - FAO & World Health Organization - WHO. CODEX ALIMENTARIUS International Food Standards - Antimicrobial Resistance. Preprint at http://www.fao.org/fao-who-codexalimentarius/thematic-areas/antimicrobial-resistance/en/.
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EUCAST: Veterinary Susceptibility Testing. http://www.eucast.org/ast_of_veterinary_pathogens/.
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Food and Agriculture Organization of the United Nations - FAO. FAOSTAT. Statistics http://www.fao.org/faostat/en/#home.
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European Food Safety Authority & European Centre for Disease Prevention and Control. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2017. European Food Safety Authority https://www.efsa.europa.eu/en/efsajournal/pub/5598 (2019).
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European Centre for Disease Prevention and Control - ECDC, European Medicines Agency - EMA & European Food Safety Authority - EFSA. ECDC/EFSA/EMA First Joint Report on the Integrated Analysis of the  Consumption of Antimicrobial Agents and Occurrence of Antimicrobial Resistance in Bacteria from Humans and Food -Producing Animals. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/01/news_detail_002260.jsp&mid=WC0b01ac058004d5c1 (2015).
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European Commission. 2013/653/EU: Commission Implementing Decision of 12 November 2013 as regards a Union financial aid towards a coordinated control plan for antimicrobial resistance monitoring in zoonotic agents in 2014. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32013D0653 (2013).
1.
The National Antimicrobial Resistance Monitoring System (NARMS). National Antimicrobial Resistance Monitoring System - Reports and Data. FDA - U.S. Food and Drug Administration http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/ucm059103.htm.
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Vyt, P., Vandepitte, L., Dereu, A. & Roozen, M. The use of tylvalosin (Aivlosin®) in the successful elimination of swine dysentery on a farrow-to-finish herd. Vlaams Diergeneeskundig Tijdschrift 81, 205–210 (2012).
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Vyt, P., Heylen, P., Neven, M. & Castryck, F. A practical approach to the elimination of swine dysentery (Brachyspira hyodysenteriae) from single-site, farrow-to-finish herds. Vlaams  Diergeneeskundig  Tijdschrift 76, 124–129 (2007).
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Rugna, G. et al. Sequence types and pleuromutilin susceptibility of Brachyspira hyodysenteriae isolates from Italian pigs with swine dysentery: 2003-2012. Vet. J. 203, 115–119 (2015).
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van Duijkeren, E. et al. Pleuromutilins: use in food-producing animals in the European Union, development of resistance and impact on human and animal health. J. Antimicrob. Chemother. 69, 2022–2031 (2014).
1.
Alvarez-Ordóñez, A., Martínez-Lobo, F. J., Arguello, H., Carvajal, A. & Rubio, P. Swine dysentery: aetiology, pathogenicity, determinants of transmission and the fight against the disease. Int J Environ Res Public Health 10, 1927–1947 (2013).
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U.S Food and Drug Administration - FDA. Press Announcements - FDA takes steps to withdraw approval of the swine drug carbadox due to safety concerns. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm494934.htm (2016).
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European Medicines Agency - EMA. Reflection paper on use of pleuromutilins in food- producing animals in the European Union: development of resistance and impact on human and animal health. Preprint at http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/02/WC500161930.pdf (2014).
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European Committee on Antimicrobial Susceptibility Testing - EUCAST & European Society of Clinical Microbiology and Infectious Diseases - ESCMID. The European Committee on Antimicrobial Susceptibility Testing. http://www.eucast.org.
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European Committee on Antimicrobial Susceptibility Testing. Clinical breakpoints. Clinical breakpoints http://www.eucast.org/clinical_breakpoints/.
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European Committee on Antimicrobial Susceptibility Testing. Antimicrobial susceptibility testing. AST of bacteria http://www.eucast.org/ast_of_bacteria/.
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