Chapter 6.5.

Harmonisation of
national antimicrobial resistance
surveillance and monitoring programmes

Article 6.5.1.

in animals and in products of animal origin intended for human consumption.

Article 6.5.2.

1. Surveillance and monitoring of antimicrobial resistance is necessary to:

   1. follow trends in antimicrobial resistance in bacteria;

   2. detect the emergence of new antimicrobial resistance mechanisms;

   3. provide the data necessary for conducting risk analyses with relevance for human and animal health;

   4. provide a basis for policy recommendations for animal and public health;

   5. provide information for prescribing practices and prudent use recommendations.

2. National antimicrobial resistance monitoring and surveillance programmes may include the following components:

   1. scientifically based surveys (including statistically based programmes);

   2. routine sampling and testing of animals on the farm, at market or at slaughter;

   3. an organised sentinel programme, sampling animals, herds, flocks, and vectors;

   4. analysis of veterinary practice and diagnostic laboratory records.

3. Countries should conduct active surveillance and monitoring. Passive surveillance and monitoring may offer additional information.

4. Targeted surveillance is conducted through an active sampling scheme designed to meet programme objectives. Passive surveillance is conducted when samples are submitted to a laboratory for testing from sources outside the programme.

Article 6.5.3.

1. General aspects

   Surveillance of antimicrobial resistance at regular intervals or ongoing monitoring of prevalence changes of resistant bacteria of animal, food, environmental and human origin, constitutes a critical part of a strategy aimed at limiting the spread of antimicrobial resistance and optimising the choice of antimicrobials used in therapy.

   Monitoring of bacteria from products of animal origin intended for human consumption collected at different steps of the food chain, including processing, packing and retailing, should also be considered.

2. Sampling strategies

   1. General

      1. Sampling should be conducted on a statistical basis. The sampling strategy should assure:

         • the sample representativeness of the population of interest;

         • the robustness of the sampling method.

      2. The following criteria are to be considered:

         • sample size;

         • sample source (animal, food, animal feed);

         • animal species;

         • category of animal within species (age group, production type);

         • stratification within category;

         • health status of the animals (healthy, diseased);

         • random sample (targeted, systematic);

         • sample specimens (faecal, carcass, processed food).

   2. Sample size

      The sample size should be:

      1. large enough to allow detection of existing resistance,

      2. not excessively large to avoid waste of resources.

      Details are provided in Table 1. Sampling fall follow standard operating procedures.

3. Sample sources

   1. Animals

      Each OIE Member should examine its livestock production systems and decide, after risk analysis, the relative importance of antimicrobial resistance and its impact on animal and human health.

      Categories of livestock that should be considered for sampling include cattle and calves, slaughter pigs, broiler chickens, layer hens and/or other poultry and farmed fish.

   2. Food and animal feed

      Contaminated food is commonly considered to be the principal route for the transfer of antimicrobial resistance from animals to humans. Plants and vegetables of different types may be exposed to manure or sewage from livestock and may thereby become contaminated with resistant bacteria of animal origin. Animal feed, including imported feed, may also be considered in surveillance and monitoring programmes.

Table 1. Sample size estimates for prevalence of antimicrobial resistance in a large population

			Level of confidence
Expected prevalence	90% Desired precision			95% Desired precision
	10%	5%	1%	10%	5%	1%
10%	24	97	2.429	35	138	3.445
20%	43	173	4.310	61	246	6.109
30%	57	227	5.650	81	323	8.003
40%	65	260	6.451	92	369	9.135
50%	68	270	6.718	96	384	9.512
60%	65	260	6.451	92	369	9.135
70%	57	227	5.650	81	323	8.003
¨80%	43	173	4.310	61	246	6.109
90%	24	97	2.429	35	138	3.445

Calculations based on Epi Info v6.04b to c Upgrade, October 1997, Centers for Disease Control
(public domain software available at hpp://www.cdc.gov/epo/epi/epiinfo.htm)

4. Sample specimens to be collected

   Faecal samples should be collected from livestock, and whole caeca should be collected from poultry. In cattle and pigs, a faecal sample size at least of 5 g provides a sufficient sample for isolation of the bacteria of concern.

   Sampling of the carcasses at the abattoir provides information on slaughter practices, slaughter hygiene and the level of faecal contamination of meat during the slaughter process. Further sampling from the retail chain provides information on prevalence changes before the food reaches the consumer.

   Existing food processing microbiological monitoring and ‘hazard analysis and critical control points’ (HACCP) programmes may provide useful samples for surveillance and monitoring of resistance in the food chain after slaughter.

5. Bacterial isolates

   The following categories of bacteria could be monitored:

   1. Animal bacterial pathogens

      Monitoring of antimicrobial resistance in animal pathogens is important, both to:

      1. detect emerging resistance that may pose a concern for human and animal health;

      2. guide veterinarians in their prescribing decisions.

      Information on the occurrence of antimicrobial resistance in animal pathogens is in general derived from routine clinical material sent to veterinary diagnostic laboratories. These samples, often derived from severe or recurrent clinical cases including therapy failure, may provide biased information.

   2. Zoonotic bacteria

      1. Salmonella

         Salmonella should be sampled from cattle, pigs, broilers and other poultry. For the purpose of facilitating sampling and reducing the concurrent costs, samples should preferably be taken at the abattoir. Surveillance and monitoring programmes may also use bacterial isolates from designated national laboratories originating from other sources.

         Isolation and identification of bacteria and bacterial strains should follow internationally accepted procedures.

         Serovars of epidemiological importance such as S. Typhimurium and S. Enteritidis should be included. The selection of other relevant serovars will depend on the epidemiological situation in each country.

         All Salmonella isolates should be serotyped and, where appropriate, phage-typed according to standard methods used at the nationally designated laboratories.

         Validated methods should be used.

      2. Campylobacter

         Campylobacter jejuni and C. coli can be isolated from the same samples as commensal bacteria. Isolation and identification of these bacteria should follow internationally accepted procedures. Campylobacter isolates should be identified to the species level.

         Agar or broth micro-dilution methods are recommended for Campylobacter susceptibility testing. Internal and external quality control programmes should be strictly adhered to.

         Validated methods with appropriate reference strains are expected to become available in the near future.

      3. Enterohaemorrhagic Escherichia coli

         Enterohaemorrhagic Escherichia coli (EHEC), such as the serotype O157, which is pathogenic to humans but not to animals, may be included in resistance surveillance and monitoring programmes.

   3. Commensal bacteria

      Escherichia coli and enterococci are common commensal bacteria. These bacteria are considered to constitute a reservoir of antimicrobial resistance genes, which may be transferred to pathogenic bacteria causing disease in animals or humans. It is considered that these bacteria should be isolated from healthy animals, preferably at the abattoir, and be monitored for antimicrobial resistance.

      Validated methods should be used.

Table 2. Examples of sampling sources, sample types and outcome of monitoring

Source	Sample type	Outcome	Additional information required/additional stratification
Herd of origin		Prevalence of resistance in bacteria originating from animal populations (of different production types) Relationship resistance - antibiotic use	Per age categories, production types, etc. Antibiotic use over time
Abattoir	Faecal	Prevalence of resistance in bacterial populations originating from animals at slaughter age
	Intestine	As above
	Carcass	Hygiene, contamination during slaughter
Processing, packing	Meat products	Hygiene, contamination during processing and handling
Retail	Meat products	Prevalence of resistance in bacteria originating from food, exposure data for consumers
	Vegetables	Prevalence of resistance in bacteria originating from vegetables, exposure data for consumers
Various origin	Animal feed	Prevalence of resistance in bacteria originating from animal feed, exposure data for animals

6. Storage of bacterial strains

   If possible, isolates should be preserved at least until reporting is completed. Preferably, isolates should be permanently stored. Bacterial strain collections, established by storage of all isolates from certain years, will provide the possibility of conducting retrospective studies.

7. Antimicrobials to be used in susceptibility testing

   Clinically important antimicrobial classes used in human and veterinary medicine should be monitored. However, the number of tested antimicrobials may have to be limited according to the financial resources of the country.

8. Type of data to be recorded and stored

   Data on antimicrobial susceptibility should be reported quantitatively.

   Appropriate validated methods should be used in accordance with Chapter I.1.10. of the Terrestrial Manual concerning laboratory methodologies for bacterial antimicrobial susceptibility testing.

9. Recording, storage and interpretation of results

   1. Because of the volume and complexity of the information to be stored and the need to keep these data available for an undetermined period of time, careful consideration should be given to database design.

   2. The storage of raw (primary, non-interpreted) data is essential to allow the evaluation of the data in response to various kinds of questions, including those arising in the future.

   3. Consideration should be given to the technical requirements of computer systems when an exchange of data between different systems (comparability of automatic recording of laboratory data and transfer of these data to resistance monitoring programmes) is envisaged. Results should be collected in a suitable national database. They shall be recorded quantitatively:

      1. as distribution of minimum inhibitory concentrations (MICs) in milligrams per litre;

      2. or inhibition zone diameters in millimetres.

   4. The information to be recorded should include at least the following aspects:

      1. sampling programme;

      2. sampling date;

      3. animal species/livestock category;

      4. type of sample;

      5. purpose of sampling;

      6. geographical origin of herd, flock or animal;

      7. age of animal.

   5. The reporting of laboratory data should include the following information:

      1. identity of laboratory,

      2. isolation date,

      3. reporting date,

      4. bacterial species,

      and, where relevant, other typing characteristics, such as:

      5. serovar,

      6. phage-type,

      7. antimicrobial susceptibility result/resistance phenotype.

   6. The proportion of isolates regarded as resistant should be reported, including the defined breakpoints.

   7. In the clinical setting, breakpoints are used to categorise bacterial strains as susceptible, intermediate susceptible or resistant. These breakpoints, often referred to as clinical or pharmacological breakpoints, are elaborated on a national basis and vary between countries.

   8. The system of reference used should be recorded.

   9. For surveillance purposes, the microbiological breakpoint, which is based on the distribution of MICs or inhibition zone diameters of the specific bacterial species tested, is preferred. When using microbiological breakpoints, only the bacterial population with acquired resistance that clearly deviates from the distribution of the normal susceptible population will be designated as resistant.

   10. If available, the phenotype of the isolates (resistance pattern) should be recorded.

10. Reference laboratory and annual reports

    1. Countries should designate a national reference centre that assumes the responsibility to:

       1. coordinate the activities related to the resistance surveillance and monitoring programmes;

       2. collect information at a central location within the country;

       3. produce an annual report on the resistance situation of the country.

    2. The national reference centre should have access to the:

       1. raw data;

       2. complete results of quality assurance and inter-laboratory calibration activities;

       3. proficiency testing results;

       4. information on the structure of the monitoring system;

       5. information on the chosen laboratory methods.

Table 3. Examples of animal bacterial pathogens
that may be included in resistance surveillance and monitoring

Target animals	Respiratory pathogens	Enteric pathogens	Udder pathogens	Other pathogens
Cattle	Pasteurella spp.	Escherichia coli	Staphylococcus  aureus
	Haemophilus  somnus	Salmonella spp.	Streptococcus spp.
Pigs	Actinobacillus  pleuropneumoniae	Escherichia coli		Streptococcus suis
		Brachyspira spp.
		Salmonella spp.
Poultry				Escherichia coli
Fish				Vibrio spp.
				Aeromonas spp.