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-Since the introduction in the 1940s of antibiotics as drugs against bacterial infections in human and then veterinary medicine, two major events have caused a shift in the antibiotherapy era: (1) the emergence of resistant bacteria and (2) the awareness of the limits of new drug development. It rapidly became urgent to set up measures in order to evaluate the importance of resistant bacteria and their origin as well as to limit the dissemination of resistant vectors (bacteria and bacterial genes). This led to the establishment of guidelines and regulatory rules necessary for risk assessment and clearly dependent upon monitoring and research organisations. At a veterinary level, the possible dissemination of multiresistant bacteria from animals to humans, through feeding, urged various national European and international institutions to give general recommendations to monitor and contain the emergence and diffusion of resistant strains. This paper gives an overview of the evolution of regulatory rules and monitoring systems dealing with multiresistant bacteria. epidemiology / surveillance / resistance to antibiotics / regulatory rules Résumé -Nouvelles tendances concernant la législation et la surveillance de la résistance aux antibiotiques chez les bactéries d'origine animale. Depuis l'introduction, dans les années 1940, des antibiotiques comme médicaments antibactériens en médecine humaine puis vétérinaire, deux évé-nements majeurs ont marqué l'ère de l'antibiothérapie : l'émergence de bactéries résistantes et la prise de conscience des possibilités limitées de développement de nouvelles molécules. Il est apparu rapidement urgent d'établir des mesures pour évaluer l'importance des résistances et leur origine ainsi que pour limiter la dissémination des vecteurs de résistance (bactéries et/ou gènes bactériens). Ceci a Vet. Res. 32 (2001) [381][382][383][384][385][386][387][388][389][390][391][392] 381

The elimination into bovine milk of beta-lactam antibiotic residues (procaine penicillin G, cloxacillin, ampicillin, oxacillin, cephalexin) following intramammary administration of 10 preparations marketed in France was studied. The quantitative analysis of residues was carried out by a microbiological agar diffusion method using Bacillus stearothermophilus. Sensitivity ranged from 0.001 I.U./ml for procaine penicillin G and 0.001 micrograms/ml for ampicillin to 0.02 micrograms/ml for cephalexin. The mean periods of elimination on which withholding times are based were between four and seven milkings according to the drugs administered.

After dosing laying hens orally with tetracycline (TC) through either drinking water (0.25 and 0.5 g/l for 5 days) or feed (300 and 600 ppm for 7 days), and chlortetracycline (CTC) through feed (600 ppm) residues were determined by an agar plate diffusion technique in cylinders with Bacillus cereus as test-organism, separately for albumen and for yolk. The sensitivity threshold was 0.07 micrograms/g in albumen and 0.15 micrograms/g in yolk for TC and 0.01 micrograms/g in albumen and 0.06 micrograms/g in yolk for CTC. Drug excretion via egg was 3-fold higher for TC than for CTC. The drug was excreted preferentially into the yolk (about 75% of the total amount) and the elimination period lasted between 6 and 11 days for TC and 9 days for CTC, after treatment. Tetracycline use in laying hens is discussed, taking into consideration the proposals presented by the joint FAO/WHO Expert Committee on Food Additives.

The kinetics of oxytetracycline elimination into eggs were determined separately for albumen and yolk after oral administration through either drinking water (0.1-0.25 and 0.5 g/l for 5 days) or feed (300 and 600 ppm for 7 days) or after intramuscular injections (3 X 15 mg/kg body weight and 3 X 30 mg/kg body weight), 24 hours apart. Residues were assayed by a microbiological agar diffusion method, with Bacillus cereus as test-organism. The detection threshold was 0.07 micrograms/g for albumen and 0.2 micrograms/g for yolk. In all cases, the elimination period lasted longer for the yolk; it varied between 0 and 10 days after treatment was discontinued, according to administration routes and dosages. The conditions of oxytetracycline utilization in laying hens are discussed. The oral route only might be used to adhere to the proposals presented by the Joint FAO/WHO Expert Committee on Food Additives.

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The elimination in cow milk of aminoglycoside antibiotic residues (neomycin, dihydrostreptomycin, kanamycin and gentamicin) was studied after intramammary administration of eight drug formulations marketed in France. Quantitative residue analysis was performed by a cylinder plate method. The sensitivity was 0.15 microgram/ml for neomycin, dihydrostreptomycin, kanamycin and 0.025 microgram/ml for gentamicin. The mean elimination periods ranged between 4 and 13 milkings. Several ways of assessing withdrawal times are discussed.