[Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study]. / Intérêt d'un gel stérile anti-brûlure dans les radiodermites : résultats d'une étude comparative.

Trial objectives were to assess effectiveness and tolerance of sterilized Avène thermal spring water anti burning gel (ATSW gel) in prevention of radiation dermatitis in adults irradiated (6 weeks) for breast (n=61) or head and neck (n=8) cancer. Patients included in this open labelled, 2 parallel groups, multicentric study, were randomly assigned to apply five times daily for ten weeks either the Avène spring water gel (n=35) or trolamine cream (n=34). The median of emergence of the first objective radiation dermatitis signs was 31 days in the ATSW gel group and 29 days in the control group (p=0,924). The median incidence for pruritus in patients of the ETA gel group was 46 days versus 27 days (p=0,028) and 44 days versus 24 days for pain (p=0,426). Global efficacy was <> in 46,7 % of patients of the ETA gel group versus 17,2 % (p=0,029) and tolerance was <> in 65,5 % of the ETA gel group versus 40,7 % (p=0,107). No radionecrosis was observed. In conclusion, the efficacy of the Avène spring water gel was similar to the control product in prophylaxis of radiation dermatitis. Tolerance was better and the pruritus was significantly more delayed in patients who applied the Avène spring water gel than in controls.

Evaluation of residual and therapeutic doses of tetracycline in the human-flora-associated (HFA) mice model.

In order to evaluate an in vivo model system for assessing the effect of therapeutic and residue levels of tetracycline on human intestinal microflora, tetracycline was administered via drinking water (1, 10, and 100 mg/liter) to human-flora-associated (HFA) male and female mice. The effects of the antibiotic on fecal aerobic and anaerobic populations, selection of bacteria resistant to tetracycline, metabolic parameters of the microflora, and maintenance of the intestinal barrier against exogenous Salmonella (resistance to colonization) were recorded. In both sexes of mice, tetracycline exposure at 10 and 100 mg/liter induced the selection of several resistant bacterial species (Gram-positive anaerobes, Bacteroides fragilis, enterobacteria, and enterococci). This effect was also observed at the lowest dose (1 mg/liter) in female mice and indicates the potential sensitivity of this endpoint for evaluating the microbiological risk of tetracycline residues. The resistance to colonization was impaired at 100 mg/liter, a concentration corresponding to about half of the therapeutic doses in humans and animals. Metabolic parameters of the microflora were not affected by tetracycline at all levels. In this study, the no-observed-effect level (NOEL) of tetracycline on intestinal flora in this study was less than 1 mg of tetracycline per liter of drinking water. This concentration in the mouse corresponds to 0.125 mg of tetracycline per kilogram of body weight per day. Within the constraints of the experimental design employed here, the HFA mice model proved to be acceptable for studying dose-related effects of tetracycline on human intestinal microflora.

New trends in regulatory rules and surveillance of antimicrobial resistance in bacteria of animal origin.

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.

Elimination of aminoglycoside antibiotics in milk following intramammary administration.

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.

Basis for the evaluation of the microbiological risks due to veterinary drug residues in food.

The history of the establishment of safe residue levels is reviewed. Current international agreements within the FAO/WHO Codex Alimentarius programme and EC legislation establish these levels on the basis of toxicology studies. In addition to conventional toxicological effects, other effects such as the effects of drugs on the immune system, and pharmacological effects should be taken into account. The latter also include specific effects of residues of veterinary antibiotics on the human gut flora. The methods for the assessment of these effects are evaluated. Studies in human volunteers enable the establishment of a no-effect level in conditions which are the most closely mimicking the conditions of use. However, they are less favourable from a practical and ethical point of view. Studies with animal models can be used; for example human intestinal flora can be inoculated to gnotobiotic mice. These models need nevertheless to be further validated. Studies in vitro, such as those to determine the MIC, are relatively simple to carry out and inexpensive, but are not always representative of the relevant bacteria, and may not take into account factors such as, Ph, anaerobiosis and the barrier effect.

Excretion of tetracycline and chlortetracycline in eggs after oral medication of laying hens.

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.

Excretion of penicillins and cephalexin in bovine milk following intramammary administration.

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.

Excretion of oxytetracycline in eggs after medication of laying hens.

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.

[Elimination of polypeptide antibiotics (colistin and bacitracin) in the milk after intramuscular or intramammary administration]. / Elimination des antibiotiques polypeptidiques (colistine et bacitracine) dans le lait après administration intramusculaire ou intramammaire.

The elimination in cow's milk of polypeptidic antibiotic residues (colistin sulfate, colistin methanesulfonate and bacitracin) was investigated following intramuscular and intramammary administrations of eight drugs marketed in France. The quantitative analysis was performed according to the microbiological method of agar diffusion. The mean elimination periods lasted between three and six milkings for injected preparations, between four and six milkings for intramammary ones. These results were used as a basis to determine the withdrawal times required on these drugs. The problem of the diffusion of the residues into milk from a quarter treated by the intramammary route, to the untreated quarters was also addressed.

Excretion of penicillins in bovine milk following intramuscular administration.

The kinetics of elimination into milk of sodium penicillin G, procaine penicillin G, benzathine penicillin G, ampicillin and amoxycillin residues have been determined after intramuscular administration of eleven drugs chosen among those commercially available in France. These investigations will be used as a basis to estimate and harmonize the withdrawal times demanded for veterinary drugs. The quantitative analysis of residues was carried out by a cylinder plate microbiological method with Bacillus stearothermophilus as test organism. The threshold of detection is 0.001 unit (or micrograms)/ml of milk. The mean durations of elimination are four milkings for the association sodium penicillin G and procaine penicillin G, from seven to eight milkings for procaine penicillin G alone, from 19 to 33 milkings for benzathine penicillin G, and from three to five milkings for ampicillin and amoxycillin.

[A survey on the use of antibiotics in veterinary medicine (author's transl)]. / Enquête sur l'utilisation des antibiotiques en médecine vétérinaire.

Many problems about public health are raised by the use of antiinfectious agents in veterinary medicine. Particular attention must be given to the contamination of human food of animal origin and to the exposure of workers manufacturing these drugs. A review of the use of these products in veterinary medicine, particularly that of antibiotics will allow to circumscribe the problems due to drugs which might cause allergy.

[General schema for safety evaluation of residues of embryotoxic drugs (author's transl)]. / Schéma général d'évaluation de la sécurité des résidus de médicaments embryotoxiques.

Concerned with adapting the withdrawal time to real risks attributed to residues, the authors present a general schema of evaluation based on the metabolism-toxicity relationship. This schema takes into account: a) possible distinction between potentially toxic and atoxic metabolites for extractable residues, b) the more or less large biovailability of residues, c) the methodological evaluation difficulties of toxicity of bound residues. Without neglecting public health, this procedure leads to less constrained restrictions in use of veterinary drugs.

High-pressure liquid chromatographic analysis of veterinary anthelmintics I: Quantitative determination of tetramisole.

High-pressure liquid chromatography was used with a 10-micron C8-type bonded silica gel column to quantitate the tetramisole in veterinary anthelmintic preparations. The chromatographic elution time was less than 10 min, and other compounds present in the products analyzed did not interefere.