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.

The efficacy of intramuscularly and intramammarily administered cefquinome was evaluated in experimental Escherichia coli mastitis in dairy cows. Forty-seven multiparous, Israeli Holstein cows in early lactation that produced at least 25 L/d of milk were used, and 400 to 750 cfu of E. coli were infused into two healthy quarters of each cow. Cows were randomly assigned to one of the following treatment groups: 1) 75 mg of cefquinome administered intramammarily three times at 12-h intervals, 2) 75 mg of cefquinome administered intramammarily three times at 12-h intervals and 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, 3) 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, and 4) 75 mg of ampicillin and 200 mg of cloxacillin administered intramammarily three times at 12-h intervals. All cows developed typical signs of acute clinical mastitis by 12 to 16 h postinoculation. Parenteral cefquinome therapy, with or without intramammary cefquinome (groups 2 and 3), significantly improved clinical recovery and return to milk production. The bacteriological cure rates were considerably and significantly higher for cows in the groups treated with cefquinome than for cows in the group treated with ampicillin and cloxacillin. This study supported the efficacy of cefquinome in the treatment of clinical coliform mastitis in dairy cows.

Absorption of 39 antibiotics from the nonlactating bovine udder was compared with absorption of [carbon-14] urea as reference. First order kinetics characterized the absorption of urea and most of the antibiotics during the first 8 to 12 h after intramammary infusion. The absorption of polymyxin B, colistin, neomycin, spiramycin, and several tetracyclines was biexponential. The physicochemical properties of drugs which appeared to govern their absorption from the udder were the degree of lipid-solubility of the nonionized fraction and the dissociation constant. Antibiotic protein binding also influenced absorption. Lipid-solubility was the rate-limiting factor with drugs that are mainly dissociated in milk at pH 6.8. These compounds were absorbed at rates related to their degree of lipid-solubility of nonionized fraction. The concentration of the nonionized molecule in milk was the rate-limiting factor with drugs that were highly lipid-soluble. Results with a number of structurally-related antiobiotics, and with others of diverse structures and physical properties, added considerable confidence to the assumption that antibiotics are absorbed from the udder by nonionic (passive) diffusion. The blood-milk barrier behaves as an inert lipoid membrane to these drugs.

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Following intramammary infusion of normal cows with a single dry cow and four lactating-cow antibiotic formulations containing penicillin G, neomycin, dihydro-streptomycin, lincomycin and framycetin, low concentrations of drug residues were detected in the kidney, urine, and for some drugs, also in blood and the liver, during the first 24 h after treatment. Drug residues were not detected in meat. In emergency-slaughtered mastitic cows, drug levels were considerably higher and persisted for a longer period than in normal cows. Persistence of drug residues is discussed in terms of the rate and extent of drug absorption from the udder, differences between normal and diseased cows, and effect of dosage form.