WAYS OF PROGRESS

5. WAYS OF PROGRESS

5.1. Research

The problem of antimicrobial resistance is one of the major topics investi- gated by research projects in the area of food safety. Epidemiological studies of food-borne disease regularly bring new knowledge on the factors influenc- ing the transfer of bacteria from animal to man. These works allow us to test new means of risk reduction following the HACCP principles. The current studies on the effect of the antimicrobial resistance on the mortality and the morbidity of pathogenic bacteria have to develop. The results of these studies

Antibiotic Use in Animals 665 allow the managers to grade the risks and to adapt the efforts of control. The

pharmacological studies of antimicrobials in animals have to integrate the effects on the pathogenic bacteria and the commensal flora. The animal individ- ual variability has to be assessed by population analysis. Finally, collection of information about usage practices by development of pharmaco-epidemiology is necessary to distinguish correct usage practices from the wrong ones. The cur- rent development of the antimicrobial usage surveillance network will allow us to develop this area as epidemiological studies in farms focusing on the rela- tionship between drug usage and antimicrobial resistance.

5.2. Training

The relationship between antimicrobial use and the selection of antimicro- bial resistance is complex. Veterinarians, as clinicians, are well trained to iden- tify diseases and diagnose etiological agents. During their initial training, microbiology and epidemiology are taught to give them a scientific back- ground of epizootic and zoonotic transmission. As future drug prescribers, the basis of pharmacology was taught by pharmacologists and the uses of antimi- crobial drugs to prevent and treat bacterial diseases were explained, during the course on animal diseases, by clinicians. The development of antimicrobial resistance is a subject which involves bacteriologists, pharmacologists, clini- cians, and epidemiologists. Unfortunately, this problem was not well devel- oped in the recent past in veterinary schools and universities. More recently, the development of resistance has been taught by bacteriologists who empha- sise the genetics and transfer of resistance between bacteria rather than by pharmacologists who should describe the relationship with dosage regimens (Lees and Aliabadi, 2000; Toutain et al., 2002), clinicians who are the key players in the choice of treatment (Lathers, 2002a), and epidemiologists who should describe the spread of antimicrobial resistance bacteria at the level of animal population and the relationship with drug usage with a global perspec- tive (Lathers, 2002b; Lipsitch et al., 2002).

In the European Union, over the last 10 years, the subject has begun to be a research area for scientific teams other than microbiologists. Some concepts developed in human medicine have to be discussed and adapted to veterinary medicine, before being taught to veterinary students and veterinary practition- ers. To reduce antimicrobial resistance, multiple and often conflicting recom- mendations have been made in human medicine (Highet et al., 1999; Lipsitch and Samore, 2002; Schentag, 2001). For example, strategies to minimise the burden of resistance in hospitals, have included reduction of all antimicrobial classes, increased use of prophylactic antimicrobials to reduce colonisation, rotation of different antibiotic classes in a temporal sequence, and simultaneous use of different antimicrobials for different patients. On the basis of these

666 Pascal Sanders varying recommendations, it is difficult to export them to veterinary medicine

without the development of experience and expertise. For example, the use of a pharmacokinetic/pharmacodynamic approach to define the dosage regimen of antibiotics has been the subject of research by several teams (Aliabadi and Lees, 2002; Lauritzen et al., 2003). The relation- ship between pharmacokinetic/pharmacodynamic surrogates and selection of resistance, notably for new fluoroquinolones products, has been discussed in human medicine and a threshold ratio for several surrogates was proposed (Highet et al., 1999). The concept has been introduced and discussed in veteri- nary medicine and different studies in animals were performed or are on- going. Unfortunately, at the same time, this concept was used in veterinary medicine by pharmaceutical companies more for product promotion than for prudent use.

Indeed, the development of an adapted antimicrobial policy needs to distin- guish the different impact of antimicrobial treatments at the individual level and at the herd level. This effect will be different according to the genetics of resistance, the pharmacology of the antimicrobial family, and use in the differ- ent animal species. The experience developed in hospital or community human medicine has to be evaluated in animal production. While prudent use of antimicrobials is encouraged by the European veterinary professional organi- sation FVE (Choraine, 2000) and the pharmaceutical industry, it remains as general as the international guidelines provided by international organisations. The technical support describing a rational use for each animal production is poorly developed. In several countries, an antimicrobial formulary has been promoted but its effect has not been measured (van Kasteren et al., 1998). Few epidemiological studies make it possible to evaluate the effect of different antimicrobials on the level of resistance in herds and on animal products. Therefore experts and teachers have difficulty in proposing technical solutions to practitioners. In Nordic countries, an antibiotic policy based on the objec- tive of reducing antimicrobial use as additives was followed by a transitory increase of antibiotic use as veterinary drugs (Wierup, 2001a, b). Another approach, applied in Germany, is a strict control of veterinary prescription and drug delivery in animal husbandry.

5.3. Information

The problem of antimicrobial resistance in non-human use is recognised and the subject of recurrent discussions between animal producers, veterinari- ans, physicians, and consumers. The recent development in the European Union of national surveillance programmes for antimicrobial resistance and drug con- sumption as well as the development of knowledge about the transmission of zoonotic agents has been driven by European policy and recommendations.

Antibiotic Use in Animals 667 Several qualitative risk analyses have been produced and are available to the

public via the Internet and several teams are dealing with the development of a quantitative risk assessment. While this information is shared between experts, it is relatively difficult to train and explain the different concepts, to animal pro- ducers and veterinarians due to the multifaceted nature of the risks. This is done during scientific and professional meetings and using professional journals. It is necessary to overcome the contradictions between human and veterinary medicine and present the problem with a global ecological perspective. The progress in the exchange of experience over the last few years, in the writing of international recommendations and the development of common investigations during zoonotic outbreaks, is the sign of an effective cooperation between veterinarians and physicians on this subject in several countries.