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Enterococcus faecalis-related amyloid arthropathy was diagnosed in a sample of birds from a flock of brown layer parent chickens aged 57 weeks. E. faecalis was isolated from amyloidotic knee joints and from blood samples from lame birds. From this flock a smaller one was kept for production purposes to study the vertical transmission of arthropathic and amyloidogenic E. faecalis. Three batches of non-soiled and thoroughly disinfected eggs, to prevent egg-shell contamination, were collected for 6 weeks and submitted for incubation every 2 weeks. No joint pathology was found in the offspring chicks (n = 458) monitored for joint disease until 16 or 21 weeks of age. Fresh and candled eggs (infertiles and dead embryos) obtained at day 18 of the incubation period had negative results at bacteriological examination of the yolk sac, except one non-hatched egg (late embryonal death in shell) from which E. faecalis was isolated. Genotyping by pulsed-field gel electrophoresis (PFGE) of all E. faecalis isolates obtained from blood and joints (except one) of the parent birds and of the non-hatched egg after Sma I digestion showed that all isolates were genetically closely related or identical to a known arthropathic and amyloidogenic E. faecalis strain. In this study, vertical transmission of E. faecalis, although it may occur on a small scale as shown by PFGE, did not seem to play a significant role. Conversely, the chronicity of the condition and the development of an immune response may have affected the efficiency of its transmission.

Recently a commercial computer-controlled image analysis system (IAS) was introduced to measure automatically the diameters of inhibition zones in the agar diffusion test. However, there is little information on the precision of this method. In the present study clinical isolates of Salmonella spp. (N = 104), Escherichia coli (N = 100), Pasteurella spp. (N = 99), Actinobacillus pleuropneumoniae (N = 85), porcine streptococci (N = 100), and Staphylococcus aureus (N = 95) were tested in the agar diffusion test, using nineteen different antibiotics in tablets. All inhibition zone diameters were first measured by a laboratory technician and then by the IAS. Although the zone diameters of all bacteria-antibiotic combinations measured by the IAS and those measured by the laboratory technician showed a significant positive correlation, the size of the inhibition zone diameters measured by the technician and the IAS differed significantly in 59% of the combinations. However, these differences were very small and may have no clinical relevance. The IAS was also used to calculate minimum inhibitory concentrations (MIC values) from the zone diameters. In 82% of the bacteria-antibiotic combinations MIC values calculated by the IAS showed a significant positive correlation with MIC values obtained with the reference agar dilution test. However, in 92% of the bacteria-antibiotic combinations, the calculated MIC values differed significantly from the reference values. In some cases these differences were so large that they could be of clinical relevance. The IAS was unable to measure the diameter of inhibition zones of porcine streptococci properly, due to poor contrast. We concluded that when tablets are used as antibiotic carriers the IAS accurately measures the diameter of inhibition zones for bacteria species that give good contrast between the agar and bacterial growth. MIC values determined with the IAS were only indicative of those determined with the reference agar dilution test.

The effect of different iron concentrations in the milk replacer on the development of iron deficiency anaemia during a fattening period of 28 weeks was studied in three groups of 14 calves. The iron contents in the milk replacer differed during the first seven weeks: 60, 100 and 150 mg Fe/kg in groups A, B and C, respectively. In all three groups blood haemoglobin, mean corpuscular volume, plasma iron concentration and saturation decreased during the fattening period, whereas the total iron-binding capacity increased. At week 7, liver iron concentrations were high with a large individual variation [A: 201 (61-706), B: 99 (47-129), C: 296 (77-1572) micrograms/g dry matter]. During the fattening period, liver iron concentrations decreased, with the lowest values at week 25 [A: 54 (34-82), B: 55 (44-83), C: 57 (42-79) micrograms/g dry matter]. Muscle iron concentrations decreased between week 7 and 19. Except plasma iron and saturation in group C, no differences in haematological and tissue iron variables were found throughout the fattening period in spite of different iron contents in the milk replacer during the first seven weeks.

The in vitro activity of flumequine in comparison with several other drugs was tested against 17 P. multocida, 16 P. haemolytica, 21 S. dublin, 21 S. typhimurium and 21 E. coli strains, isolated in (veal) calves in the Netherlands. The MIC50 of flumequine for the respective pasteurellas was 0.25 and 1 microgram/ml, for the salmonellas and E. coli 0.5 micrograms/ml. In comparison with flumequine, enrofloxacin and ciprofloxacin showed higher in vitro activity, with MIC50 less than or equal to 0.008 micrograms/ml for ciprofloxacin. Decreased susceptibility of the pasteurellas was found for kanamycin, neomycin, streptomycin, gentamicin, oxytetracycline and doxycycline. The MIC50 of minocycline for P. multocida was 0.5 micrograms/ml and there was no cross resistance with the other tetracyclines. P. multocida was very susceptible to ampicillin (MIC50 less than or equal to 0.03 micrograms/ml), P. haemolytica, however, was 100% resistant to this drug. Both pasteurellas were susceptible to cephalothin and approximately 50% of the strains of both bacteria were resistant to chloramphenicol. The MIC50 of either spiramycin or tylosin was greater than or equal to their respective breakpoint-MIC values. Both pasteurellas were susceptible to the combination of trimethoprim and sulphamethoxazole. However, for P. multocida, the addition of sulphamethoxazole to trimethoprim had no synergistic effect on its MIC. In comparison with trimethorpim, aditoprim was less potent. Therefore only P. multocida was susceptible to aditoprim.

Pharmacokinetics and tissue distribution experiments were conducted in pigs to which sulphadimidine (SDM) was administered intravenously, orally, and intramuscularly at a dosage of 20 mg SDM/kg. SDM was acetylated extensively, but neither hydroxy metabolites nor their derivatives could be detected in plasma, edible tissues or urine. Following i.v. and two oral routes of administration, the N4-acetylsulphadimidine (N4-SDM) concentration-time curve runs parallel to that of SDM. The percentage of N4-SDM in plasma was in the range between 7 and 13.5% of the total sulphonamide concentration. The bioavailability of SDM administered in a drench was 88.9 +/- 5.4% and administered mixed with pelleted feed for 3 consecutive days it was 48.0 +/- 11.5%. The renal clearance of unbound SDM, which was urine flow related, was 1/7 of that of creatinine, indicating reabsorption of the parent drug. The unbound N4-SDM was eliminated three times faster than creatinine, indicating that tubular secretion was the predominant mechanism of excretion. After i.v. administration, 51.9% of the administered dose was recovered in urine within 72 h p.i., one quarter of which as SDM and three quarters as N4-SDM. Tissue distribution data obtained at 26, 74, 168, and 218 h after i.m. injection revealed that the highest SDM concentration was found in plasma. The SDM concentration in muscle, liver, and kidney ranged from one third to one fifth of that in plasma. The N4-SDM formed a minor part of the sulphonamide content in edible tissues, in which the SDM as well as the N4-SDM concentration parallelled the plasma concentrations. Negative results obtained with a semi-quantitative bioassay method, based on monitoring of urine or plasma, revealed that the SDM concentration levels in edible tissues were in that case below 0.1 mu/g tissue.

The oral absorption and bioavailability of flumequine was studied in 1-, 5- and 18-week-old calves following intravenous and oral administration of different formulations of flumequine (Flumix, Flumix C and pure flumequine). Increasing age had a negative influence on the Cmax after the administration of Flumix, based on a larger VD in the older calves. The Cmax decreased from 5.02 +/- 1.46 micrograms/ml in the first week to 3.28 +/- 0.42 micrograms/ml in the 18th week. Adding colistin sulfate to the flumequine formulation and administring pure flumequine mixed with milk replacer had a negative effect on the Cmax of flumequine after oral administration of 5 and 10 mg/kg body weight. The bioavailability of the orally administered flumequine formulations was 100% in all cases except after the administration of Flumix C, for which it was 75.9 +/- 18.2%. The urinary recovery of flumequine after intravenous injection of a 10% solution varied from 35.2 +/- 2.3% for Group B, to 41.2 +/- 6.3% for Group C. The dosage of 5 mg/kg body weight Flumix twice daily in 1-week-old veal calves is sufficient to reach therapeutic plasma concentrations, based on a MIC value of 0.8 micrograms/ml of the target bacteria. In older calves it is advisable to increase the dosage 7.5 or 10 mg/kg body weight every 12 hours. In combination with colistin sulfate it is also advisable to increase the dosage slightly because of the negative effect of the colistin sulfate on the Cmax of flumequine.

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vf: 1.62 l/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half-lives were in the range between 11.6 and 17.2 hrs. The mean OTC binding to plasma proteins was 75.5 +/- 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 micrograms/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 +/- 0.06 microgram/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 microgram/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 microgram/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 +/- 0.67%, and after medicated pelleted feed administration 3.69 +/- 0.8%. The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P less than 0.005), being 3-5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.

The pharmacokinetics of ciprofloxacin, a quinoline derivative with marked bactericidal activity against gram-negative bacteria, was studied in calves and pigs following intravenous and oral administration. Ciprofloxacin was rapidly and well distributed in the body, exhibited a short elimination half-life of 2.5 h in both species, and was rapidly absorbed after oral administration (Tmax:2 to 3 h). The oral bioavailability in calves was 53 +/- 14% and for 1 pig 37.3%. The renal clearance of the unbound ciprofloxacin for both species was of the same order, indicated a predominantly tubular secretion pattern, and accounted for about 46% of the total drug elimination. No complete drug mass balance could be demonstrated. Small amounts of two metabolites were detected in the urine of calves, but not in pig urine.

Oxytetracycline (OTC) concentrations on plasma and milk of dairy cows were determined following a single intramuscular injection of five oxytetracycline-20% formulations at a dosage of approximately 10 mg/kg. For obtaining pharmacokinetic reference parameters, one 10% OTC formulation was administered intravenously. The five 20% formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half-life, and relative bioavailability. The mean maximum plasma OTC concentrations varied between 4.5 and 6.8 micrograms/ml and were achieved between 5 and 10 h p.i., depending on the formulation involved. The mean maximum milk concentrations, ranging from 1.12 to 1.92 micrograms/ml, were achieved 12 to 24 h p.i. A plasma OTC concentration exceeding 0.5 microgram/ml was maintained for 48 h to 70 h, and in milk for 33 to 49 h, depending on the formulation involved. Formulations exhibiting the lowest clinically noticeable irritation showed the highest peak plasma OTC concentrations and the best bioavailability. Among the formulations the calculated withholding periods for milk were in the range of 3 to 4 days and for edible tissues of 9 to 14 days. The OTC and creatinine clearances were significantly correlated to each other and to the urinary flow. OTC was excreted predominantly by glomerular filtration, partly by tubular secretion minus urogenital (distal renal tubuli and bladder) reabsorption.

In plasma and milk the oxytetracycline (OTC) concentrations were determined following a single intramuscular administration of eight 10%-formulations to dairy cows at a dose of approximately 5 mg/kg. Two of these formulations were injected intravenously to obtain reference values of the drug's pharmacokinetic parameters. The eight formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half-life, and relative bioavailability. The mean maximum plasma OTC concentrations, ranging from 2.0 to 4.1 micrograms/ml, were achieved between 4 and 12 hours post injection, depending on the formulation involved. The mean maximum milk OTC concentrations, in the range between 0.92 and 1.43 micrograms/ml, were achieved 12 to 24 h p.i. The OTC milk concentration-time profile ran parallel to the OTC plasma concentration-time profile. After intravenous administration the time for the appearance of OTC in milk was shorter (1-2 hours p.i.), the peak milk OTC concentration was higher (1.7-1.9 micrograms/ml) and achieved earlier (6-8 h p.i.), and the OTC persistence in milk shorter than after i.m. administration. Formulations exhibiting the lowest clinically noticeable irritation showed the most favourable pharmacokinetic characteristics: rapid absorption with the highest peak plasma OTC concentrations and good bioavailability. The plasma and milk protein binding for OTC was respectively 71.7 +/- 7.4% and 84.8 +/- 5.45%. Withdrawal times for milk and edible tissues are presented on the basis of preset tolerance or detection limits.