Antimicrobial resistance: risk analysis methodology for the potential impact on public health of antimicrobial resistant bacteria of animal origin.

The Ad hoc Group of experts on antimicrobial resistance, appointed by the Office International des Epizooties, has developed an objective, transparent and defensible risk analysis process, providing a valid basis for risk management decisions in respect to antimicrobial resistance. The components of risk analysis and of different possible approaches in risk assessment (qualitative, semiquantitative and quantitative) are defined. The Ad hoc Group recommended the following: an independent risk assessment based on scientific data; an iterative risk analysis process; a qualitative risk assessment systematically undertaken before considering a quantitative approach; the establishment of a risk assessment policy; and the availability of technical assistance for developing countries.

Antimicrobial resistance: responsible and prudent use of antimicrobial agents in veterinary medicine.

A guideline on the responsible and prudent use of antimicrobials in animal husbandry has been developed by the Ad hoc Group of experts on antimicrobial resistance, created by the Office International des Epizooties. The objectives of responsible use are to maintain antibiotic efficacy, to avoid the dissemination of resistant bacteria or resistance determinants and to avoid the exposure of humans to resistance through food. The guideline attributes a central role to the competent authorities responsible for granting marketing authorizations for antimicrobial substances. Requirements before and after granting of marketing authorizations are defined. Important aspects include the control of the pharmaceutical product quality and the therapeutic efficacy, the assessment of the selection pressure, the protection of the environment, specific and non-specific antimicrobial resistance surveillance. The guideline is also addressed to the veterinary pharmaceutical industry, veterinary practitioners, dispensing pharmacists and farmers. The respective roles and responsibilities of these groups are defined.

Antimicrobial resistance: monitoring the quantities of antimicrobials used in animal husbandry.

This guideline, developed by the Office International des Epizooties for the monitoring of the quantities of antimicrobials used in animal husbandry, provides the methodology required to assess the amounts of antimicrobials used, to supply data to be used for risk analysis and to improve guidance on the appropriate use of antimicrobials. Information may be gathered from a number of sources, such as the competent authorities, industry and users. The usefulness of different types of information is discussed and recommendations are given on how to collect detailed information, each year, on the antimicrobial quantities used per class and active substance. Information should also be collected on the route of administration (oral and parenteral) and the animal species.

Antimicrobial resistance: standardisation and harmonisation of laboratory methodologies for the detection and quantification of antimicrobial resistance.

The Ad hoc Group of experts on antimicrobial resistance of the Office International des Epizooties has developed a guideline on the standardisation and harmonisation of laboratory methodologies used for the detection and quantification of antimicrobial resistance. The existing methods (disk diffusion [including concentration gradient strips], agar dilution and broth dilution) are reviewed, including a comparison of their advantages and disadvantages. The definitions of resistance characteristics of bacteria (susceptible, intermediate and resistant) are addressed and the criteria for the establishment of breakpoints are discussed. Due consideration has to be given to these aspects in the interpretation and comparison of resistance monitoring or surveillance data. The use of validated laboratory methods and the establishment of quality assurance (internal and external) for microbiological laboratory work and the reporting of quantitative test results is recommended. Equivalence of different methods and laboratory test results is also recommended to be established by external proficiency testing, which should be achieved by the means of a reference laboratory system. This approach allows the comparison of test results obtained using different methods generated by laboratories in different countries.

Antimicrobial resistance: harmonisation of national antimicrobial resistance monitoring and surveillance programmes in animals and in animal-derived food.

A guideline on the harmonisation of national antimicrobial resistance monitoring and surveillance programmes in animals and animal-derived foods has been developed by the Ad hoc Group of experts on antimicrobial resistance of the Office International des Epizooties. The objective of the guideline is to allow the generation of comparable data from various national surveillance and monitoring systems in order to compare the situations in different regions or countries and to consolidate results at the national, regional and international level. Definitions of surveillance and monitoring are provided. National systems should be able to detect the emergence of resistance, and to determine the prevalence of resistant bacteria. The resulting data should be used in the assessment of risks to public health and should contribute to the establishment of a risk management policy. Specific factors identified for harmonisation include the animal species, food commodities, sampling plans, bacterial species, antimicrobials to be tested, laboratory methods, data reporting, database structure and the structure of reports.

The application of quantitative risk assessment to microbial food safety.

Quantitative risk assessment (QRA) is rapidly accumulating recognition as the most practical method for assessing the risks associated with microbial contamination of foodstuffs. These risk analyses are most commonly developed in commercial computer spreadsheet applications, combined with Monte Carlo simulation add-ins that enable probability distributions to be inserted into a spreadsheet. If a suitable model structure can be defined and all of the variables within that model reasonably quantified, a QRA will demonstrate the sensitivity of the severity of the risk to each stage in the risk-assessment model. It can therefore provide guidance for the selection of appropriate risk-reduction measures and a quantitative assessment of the benefits and costs of these proposed measures. However, very few reports explaining QRA models have been submitted for publication in this area. There is, therefore, little guidance available to those who intend to embark on a full microbial QRA. This paper looks at a number of modeling techniques that can help produce more realistic and accurate Monte Carlo simulation models. The use and limitations of several distributions important to microbial risk assessment are explained. Some simple techniques specific to Monte Carlo simulation modelling of microbial risks using spreadsheets are also offered which will help the analyst more realistically reflect the uncertain nature of the scenarios being modeled. simulation, food safety.

Risk analysis in relation to the importation and exportation of animal products.

The design of a quantitative risk analysis model has to be dictated by the questions it seeks to answer. The model should also be as objective as the available data will allow. Animal and animal product import risks usually have three characteristics which make the design of a good quantitative risk analysis model quite difficult, namely:--the probabilities of the steps leading to the undesired outcome are frequently inter-related--the probability of the undesired outcome itself is in many cases very small, making direct simulation impractical--important variables within the model often cannot be quantified through analysis of data, thus these variables must be modelled with probability distributions to reflect the degree of uncertainty, usually determined by expert opinion. This paper provides a tutorial on some modelling techniques which are essential to the risk assessment of animal and animal product imports and which help overcome these problems. A number of probability distributions, their uses and inter-relationships, are examined. The application of these distributions, coupled with some general modelling techniques, is then demonstrated to produce rigorous and transparent animal import risk analyses.

Contamination of animal products: the minimum pathogen dose required to initiate infection.

When an animal product contains a low level of contamination (perhaps less than the minimum infective dose of a pathogen as determined experimentally), the theoretical probability remains that if a large number of animals are exposed to that product, at least one animal in the group will become infected. Such an infected animal could start an outbreak of the disease. These aspects, therefore, should be considered when risk assessments are performed. Foot and mouth disease virus in milk is used as an example.

Determination of continuous atracurium infusion rate in dogs undergoing whole-body hyperthermia.

Infusion rates for atracurium were calculated from multiple bolus injection data for normothermic (38 degrees C; n = 4) and hyperthermic (42 degrees C; n = 14) dogs anesthetized with thiopental and oxymorphone while undergoing whole-body hyperthermia treatment. The calculated infusion rate for atracurium at 38 degrees C was 6.2 +/- 0.3 micrograms/kg/min and the calculated infusion rate at 42 degrees C was 8.5 +/- 0.4 micrograms/kg/min. Infusion of atracurium at the calculated infusion rate of 8.5 micrograms/kg/min produced an estimated 90-100% neuromuscular blockade during heating from 38-42 degrees C and at 42 degrees C. Following discontinuation of the infusion and cooling to 38 degrees C, neuromuscular function returned to normal within 20 min with no evidence of recurarization. Atracurium infusion rates appear to be linear and related to body temperature from 26-42 degrees C. Clinically useful neuromuscular blockade in dogs may be obtained during whole-body hyperthermia by utilizing the 42 degrees C atracurium infusion rate throughout the 38-42 degrees C heating phase.