The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 112 Staphylococcus aureus isolates from the bovine udder was 0.78 microgram/mL and 149 of 164 (90.8%) other gram-positive udder pathogens were inhibited by tilmicosin concentrations < 3.12 micrograms/mL. The MIC of the drug for 19 of 22 S. aureus isolates was < 0.78 microgram/mL when the test was conducted using Mueller-Hinton (MH) agar or MH agar containing 7.5% skimmed milk. Acute cardiac toxicity followed intravenous (i.v.) injection of the drug at 10 mg/kg to 3 cows, but animals appeared clinically normal within 30 min after treatment. The pharmacokinetics of i.v.-administered tilmicosin is typical for the macrolide class of antibiotics, i.e. low serum drug concentrations and a large volume of distribution (> 2.0 L/kg). The elimination half-life (t1/2 beta) values for 3 cows were 46.4, 56.0 and 72.8 min. The drug was administered subcutaneously (s.c.) to 5 cows at 10 mg/kg; the elimination half-life (t1/2el) was 4.18 +/- 0.55 h and the mean s.c. bioavailability was 22%. Rapid and extensive penetration of tilmicosin from blood into milk, and slow elimination from the milk were among the characteristic kinetic features of the drug after i.v. and s.c. administration. Tilmicosin was injected s.c. at 10 mg/kg once to 9 cows after the last milking of lactation; dry udder secretion samples were collected daily for 11 consecutive days and assayed microbiologically. Concentrations of drug > 0.78 microgram/mL were found in the secretion for 8-9 days after dosing. Systemic side-effects were not observed after s.c. drug administration.

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The single-dose disposition kinetics of danofloxacin were determined in clinically normal lactating cows after intravenous (i.v.) and intramuscular (i.m.) administration of the drug at 1.25 mg/kg. The drug concentrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis. The mean i.v. and i.m. elimination half-lives (t1/2el) in serum were 54.9 and 135.7 min, respectively. The steady-state volume of distribution (Vss) was 2.04 L/kg. The drug was quickly absorbed after i.m. injection but a 'flip flop' effect was clearly evident and bioavailability was > 100%. Penetration of danofloxacin from blood into milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 90-120 min after i.v. and i.m. administration and onwards. Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over approximately 24 h. Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.

Coagulase-negative staphylococci (CNS) are the most frequently isolated bacteria from bovine mammary gland milk samples. The objective of this study was to determine the type of inflammation evoked by CNS in the mammary gland of cows during their first lactation. Twenty-four Israeli-Holstein heifers in their first lactation were tested for bacteriological status, somatic cell count (SCC) and differential leucocyte count in milk 60-120 days postparturition and every 50-60 days after until drying off. Following the first testing, the 96 quarters of the 24 heifers were classified as follows: 69.8 % as no bacterial growth (NBG), 27.1 % infected with CNS and 3.1 % infected with Staphylococcus aureus. During lactation, 84.5 % quarters had no change in their classification, 6.2 % were newly infected with other pathogens, 3.1 % were classified as self-cured and in 6.2 % sporadic bacteria were isolated. Among the CNS, S. intermedius, S. chromogenes and S. haemolyticus were the most frequently isolated. Milk from CNS-infected quarters had significantly higher SCC than milk from NBG quarters. An analysis of the leucocyte pattern in milk from CNS vs. NBG quarters revealed a significant increase in polymorphonuclears and a significant decrease in the percentage of total lymphocytes and lymphocytes bearing CD4 + or CD8 + . The high percentage of CNS-infected quarters that remained unchanged in their bacterial status during the first lactation, indicates that those CNS have the ability to elude the immune system and persist in the mammary gland for a long time. The persisting infection, resulting to some extent from an increase of SCC by some CNS strains, suggests that in the near future control steps will have to be taken into consideration, in order to enhance the improvement of milk quality.

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